nmnwiki - User contributions [en]

Washington University

2020-06-29T21:00:59Z

JW008:

Washington University in St. Louis is a private research university located in St. Louis, Missouri. The university is home to Dr. Shin-Ichiro Imai's research [https://imailab.wustl.edu/ lab], which is a part of the Department of Developmental Biology. Dr. Imai's lab is focused on understanding the molecular changes associated with the aging process. His lab has been active in understanding the role of sirtuins in the aging process and investigating the potential utility of NMN and NR as treatments for aging.

==Published Research Articles==
[[Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice]]

==Notable Figures in NMN Research==

*[[Shin-ichiro Imai|Dr. Shin-ichiro Imai]]

[[Category:Institutions]]
[[Category:Full index]]

University of Oklahoma

2020-06-29T20:57:48Z

JW008:

The University of Oklahoma is a public research institution located in Tulsa, Oklahoma. The University of Oklahoma is home to the Reynolds Oklahoma Center for [https://www.ouhsc.edu/roca/ Aging (ROCA)], a collaborative research institute composed of six aging-focused research labs. Dr Zoltan Ungvari, whose lab is a member of the ROCA, is focused on better understanding the effects of aging on the cardiovascular and cerebrovascular systems.

==Published Research Articles==
[[Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice]]

==Notable Figures in NMN Research==

*[[Zoltan Ungvari]]

[[Category:Institutions]]
[[Category:Full index]]

University of New South Wales

2020-06-29T20:53:21Z

JW008:

The University of New South Wales is an Australian public research university located in Sydney, Australia. Notable alumni include Dr. David Sinclair, who now heads his own anti-aging research group at Harvard Medical School.

The University of New South Wales is home to the Laboratory for Aging Research [https://medicalsciences.med.unsw.edu.au/research/groups/metabolic-disease/molecular-biology-ageing]. The laboratory is currently funded by several grants from the Australian National Health and Medical Research Council to support ongoing research into the biochemical underpinnings of the aging process as well as potential therapies to treat aging.

==Published Research Articles==
[[Head to head comparison of short term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide(NMN) and 6 weeks of exercise in obese female mice]]

==Notable Figures in NMN Research==

*[[Margaret Morris]]

[[Category:Institutions]]
[[Category:Full index]]

Keio University

2020-06-29T20:49:11Z

JW008:

Keio University is a private university located in Tokyo, Japan. It was established in 1858 and is regarded as the oldest institution of higher learning in Japan. The University has the unique distinction of being the first organization to publish a clinical study evaluating the pharmacology of NMN in humans. Dr. Hiroshi Itoh's lab is an active NMN-focused research lab located at Keio University.

==Published Research Articles==
[[Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men]]

==Notable Figures in NMN Research==

*[[Hiroshi Itoh|Dr. Hiroshi Itoh]]
*[[Shin-ichiro Imai]]

[[Category:Institutions]]
[[Category:Full index]]

Harvard

2020-06-29T20:47:12Z

JW008:

Harvard Medical School (HMS) is the medical school and medical science research wing of Harvard University. The medical school was founded in 1782 and is considered a leader in the United States for basic science and translational medical research.

The [https://genetics.med.harvard.edu/sinclair/people/sinclair.php Sinclair Lab], headed by David Sinclair, PhD, is part of the Blavatnik Institute for Genetics at Harvard Medical School. Dr. Sinclair's lab has been a leader in performing anti-aging research, and evaluating the anti-aging properties of compounds such as NMN.

==Published Research Articles==
[[Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice]]

==Notable Figures in NMN Research==

*[[David Sinclair]]

[[Category:Institutions]]
[[Category:Full index]]

Harvard

2020-06-29T20:46:29Z

JW008:

Harvard Medical School (HMS) is the medical school and medical science research wing of Harvard University. The medical school was founded in 1782 and is considered a leader in the United States for basic science and translational medical research.

The Sinclair Lab, headed by David Sinclair, PhD, is part of the Blavatnik Institute for Genetics at Harvard Medical School. Dr. Sinclair's lab has been a leader in performing anti-aging research, and evaluating the anti-aging properties of compounds such as NMN.

==Published Research Articles==
[[Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice]]

==Notable Figures in NMN Research==

*[[David Sinclair]]

[[Category:Institutions]]
[[Category:Full index]]

Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice

2020-06-11T20:17:53Z

JW008: /* Institution */

'''Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice''' is a mouse study which investigated the effects of [[NMN supplementation]] on neurovascular coupling and endothelial functioning in aged mice. The three experimental groups were young mice, aged control mice, and aged mice treated for 14 days with 500mg/kg of [[NMN]] injected intra-peritoneally. The authors found that although in aging control mice, brain endothelial [[NAD+|NAD+]] was decreased to about 70% of young mice, treatment with NMN was associated in a statistically significant increase in NAD+ to about the level of healthy young mice (p < 0.05). The authors further reported that NMN supplementation was associated with improved cerebral blood flow in response to stimulus, demonstrating that the associated increase in young mice and NMN treated mice was approximately 20% compared to 10% in aged control mice (p < 0.05). Additional confirmatory studies conducted by the authors affirmed that the improvement in endothelial function was mitochondrially mediated and were associated with improved functioning of the mitochondria rather than simply increased numbers of mitochondria. With respect to behavior tests which assessed cognitive function, the authors found that NMN supplementation improved learning latency in aging mice, mirroring the results of the young cohort. In addition, NMN supplementation improved novel object recognition testing in the aging cohort as well. <ref>Tarantini S, Valcarcel-Ares MN, Toth P, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. ''Redox Biol''. 2019;24.</ref>

==Article abstract==
Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI).

==Implications==
Overall, this study adds to the growing body of literature that NMN supplementation appears to result in tangible improvements in mitochondrial functioning on an in vitro basis. This study takes these results further by showing the physiologic results of these improvements via the improvement of neurovascular coupling and cerebral blood flow in NMN-treated aged mice. Additional behavior studies in these mice highlighted the potential cognitive benefits of these previously established in vitro improvements.

==Additional research to be conducted==
The authors report in their manuscript that future planned directions of study will investigate previously reported relationships between hydrogen sulfide and aging. Specifically, the authors note that since previous studies have highlighted the potentially beneficial role of hydrogen sulfide in reversing vascular aging, they would recommend investigating the interaction between hydrogen sulfide and known NAD+ metabolic pathways.

In addition to this topic, which was highlighted within the manuscript, future directions for this research could involve non-invasively measuring the blood flow effects that oral NMN supplementation has in humans. Recent work has highlighted the safety and efficacy of oral NMN supplementation in humans already, and investigations into the potential effects of this supplementation should follow.<ref>Irie J, Inagaki E, Fujita M, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. ''Endocr J''. 2020;67(2):153-160.</ref>

==Institution==
Dr. Zoltan Ungvari has published extensively on topics ranging including [[Epigentics of aging|aging]] and mitochondrial health and effects that aging has on the vasculature from his lab at the [[University of Oklahoma]]. Prior to this article they had published numerous articles investigating the effects of NMN and [[Resveratrol|resveratrol]] on mitochondrial functioning and endothelial health.<ref>Kiss T, Giles CB, Tarantini S, et al. Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects. ''GeroScience''. 2019;41(4):419-439.</ref><ref>Kiss T, Nyúl-Tóth Á, Balasubramanian P, et al. Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects. ''GeroScience''. February 2020.</ref><ref>Kiss T, Balasubramanian P, Valcarcel-Ares MN, et al. Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment. ''GeroScience''. 2019;41(5):619-630.</ref>

==Funding==
This study was funded by grants from the American Heart Association, the National Institute on Aging, and the National Institute of Neurologic Disorders and Stroke, among others. The authors report no industry sources of funding and note the funding sources had no input into study design, review, or publication.

==Authors/ Researchers==

*Stefano Tarantini – Department of Geriatric Medicine, University of Oklahoma
*Marta Valcarcel-Ares - Department of Geriatric Medicine, University of Oklahoma
*Peter Toth - Department of Geriatric Medicine, University of Oklahoma
*Andriy Yabluchanskiy - Department of Geriatric Medicine, University of Oklahoma
*Zsuzsanna Tucsek - Department of Geriatric Medicine, University of Oklahoma
*Tamas Kiss - Department of Geriatric Medicine, University of Oklahoma
*Peter Hertelendy - Department of Geriatric Medicine, University of Oklahoma
*Michael Kinter – Aging and Metabolism Research Program, Oklahoma Medical Research Foundation
*Praveen Ballabh – Department of Pediatrics, Albert Einstein College of Medicine
*Zoltan Sule – Department of Anatomy, University of Szeged
*Eszter Farkas – Department of Medical Physics, University of Szeged
*Joseph A. Baur – Department of Physiology, University of Pennsylvannia
*[[David Sinclair|David A. Sinclair]] – Department of Genetics, Harvard Medical School
*Anna Csiszar – Department of Public Health, Semmelweis University
*Zoltan Ungvari - Departments of Geriatric Medicine, Health Promotion Sciences, University of Oklahoma; Department of Medical Physics, University of Szeged; Department of Public Health, Semmelweis University

==References==
<references />
[[Category:Research]]
[[Category:Full index]]

University of Oklahoma

2020-06-11T20:17:39Z

JW008: Created page with "The University of Oklahoma is a public research institution located in Tulsa, Oklahoma. ==Published Research Articles== Nicotinamide mononucleotide (NMN) supplementation re..."

The University of Oklahoma is a public research institution located in Tulsa, Oklahoma.

==Published Research Articles==
[[Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice]]

==Notable Figures in NMN Research==
*[[Zoltan Ungvari]]

[[Category:Institutions]]
[[Category:Full index]]

Head to head comparison of short term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide(NMN) and 6 weeks of exercise in obese female mice

2020-06-11T20:15:40Z

JW008: /* Institution */

This study compared the changes associated with NMN or exercise interventions in mice. The 60 mice were separated into 5 groups: chow sedentary, chow exercise, high-fat diet (HFD) sedentary, HFT with NMN, and HFT with exercise. After 6 weeks of diet, the animals in the exercise intervention began 6 weeks of 6 day / week exercise regimen. Mice in the NMN group received 500 mg/kg NMN intra-peritoneally for the last 17 days of the study. Following 6 weeks of their respective diets, the mice in the HFD group were 23% heavier than the chow-fed mice. In the HFD mice, the authors found that both NMN and exercise improved insulin sensitivity, as evidenced by the area under the curve of a glucose vs. time graph following feeding (p < 0.05 for both compared to HFD sedentary). Additionally, the authors found that HFD was associated with lower NAD+ in liver and skeletal muscle tissues and that NMN treatment increased NAD+ levels in both tissues, whereas exercise only significantly increased NAD+ in muscle tissue. In addition, citrate synthase, an enzyme which is associated with mitochondrial activity, was reduced in muscle and liver in mice on the HFD. Exercise resulted in significant increases in citrate synthase activity in skeletal muscle while NMN supplementation did not, and NMN supplementation and exercise both resulted in increased activity in liver tissue<ref>Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Front Pharmacol. 2016;7(AUG)</ref>.

== Article Abstract ==
Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD(+) levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD(+) only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

== Implications ==
This article highlighted not only the pathology associated with high-fat diet (HFD), but also the potential utility of NMN in addressing this pathology. Specifically, this research showed that both exercise and NMN supplementation were effective in addressing some of the changes that resulted from HFD; however, there appeared to be tissue-specific differences in these effects. This is important, because NMN tended to exert more change in the liver, whereas the benefits from exercise were seen primarily in the muscle tissue. This could mean that NMN may be effective in reversing some of the more systemic negative effects of HFD such as fatty liver.

== Additional Research to be Conducted ==
Future work will likely continue to build upon the findings made in this report – that NMN and exercise exert different effects on different tissues. The authors of this study note that their future work may focus on identifying exactly why NMN supplementation seems to affect liver mitochondrial function whereas exercise’s effects on mitochondria seem specific to skeletal muscle.

== Institution ==
Dr. Morris’ lab is located at the [[University of New South Wales]]. Her group has published several other papers investigating the potential applications of NMN to improve obesity-related disease as well as male and female reproductive health<ref>Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: Comparison with exercise. Sci Rep. 2017;7(1)</ref><ref>Uddin GM, Youngson NA, Chowdhury SS, Hagan C, Sinclair DA, Morris MJ. Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers. Cells. 2020;9(4):791.</ref><ref>Youngson NA, Mezbah Uddin G, Das A, et al. Impacts of obesity, maternal obesity and nicotinamide mononucleotide supplementation on sperm quality in mice. Reproduction. 2019;158(2):169-179.</ref>.

== Funding ==
This research was funded by the National Health and Medical Research Council (NHMRC).

== Authors/Researchers ==
*Golam Uddin – Department of Pharmacology, University of New South Wales
*Neil Youngson - Department of Pharmacology, University of New South Wales
*[[David Sinclair]] – Department of Genetics, Harvard Medical School
*Margaret Morris - Department of Pharmacology, University of New South Wales

== References ==
[[Category:Research]]
<references />
[[Category:Full index]]

University of New South Wales

2020-06-11T20:15:13Z

JW008: Created page with "The University of New South Wales is an Australian public research university located in Sydney, Australia. ==Published Research Articles== Head to head comparison of short..."

The University of New South Wales is an Australian public research university located in Sydney, Australia.

==Published Research Articles==
[[Head to head comparison of short term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide(NMN) and 6 weeks of exercise in obese female mice]]

==Notable Figures in NMN Research==
*[[Margaret Morris]]

[[Category:Institutions]]
[[Category:Full index]]

Keio University

2020-06-11T20:11:38Z

JW008: Created page with "Keio University is a private university located in Tokyo, Japan. It was established in 1858 and is regarded as the oldest institution of higher learning in Japan. ==Publishe..."

Keio University is a private university located in Tokyo, Japan. It was established in 1858 and is regarded as the oldest institution of higher learning in Japan.

==Published Research Articles==
[[Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men]]

==Notable Figures in NMN Research==
*[[Hiroshi Itoh|Dr. Hiroshi Itoh]]
*[[Shin-ichiro Imai]]

[[Category:Institutions]]
[[Category:Full index]]

Oriental Yeast Company

2020-06-11T20:08:25Z

JW008: Created page with "Oriental Yeast Company (OYC) was the first yeast technology company founded in Japan. The company was founded in 1929, and today is focused on producing food products, includi..."

Oriental Yeast Company (OYC) was the first yeast technology company founded in Japan. The company was founded in 1929, and today is focused on producing food products, including high quality [[NMN]]. They're also a supporter and funder of academic research investigating the potential benefits of [[NMN]] supplementation.

==Published Research Articles==
[[Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice]]

==Notable Figures in NMN Research==
*Shoehi Yoshida
*Koji Uchida - Oriental Yeast Company

[[Category:Institutions]]
[[Category:Full index]]

Nicotinamide mononucleotide , a key NAD+ intermediate , treats the pathophysiology of diet- and age- induced diabetes in mice

2020-06-11T20:04:30Z

JW008: /* Institution */

'''Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice''' In this study, Yoshino et al. investigated the role of NMN in an animal model of type 2 diabetes (T2D). The authors induced T2D with a high-fat diet, and then administered 500 mg / kg of NMN over 7 or 10 days. The authors found that in untreated mice with T2D, NAD+ biosynthesis was severely diminished in white adipose tissue (WAT) and hepatocytes. Following NMN administration, the authors observed at 15x increase in intracellular NMN, as well as a 5x increase in hepatocyte nicotinamide riboside (NR). The authors also found that NMN supplementation improved insulin-response in T2D mice, in females by improving insulin sensitivity, while in males by improving glucose-stimulated insulin secretion. They were unsure of the exact reason for gender-specific responses to NMN. They also found that Sirtuin 1 was one of the mediators of the improvements associated with NMN, and that treatment with NMN also improved metabolic complications of T2D in these mice<ref>Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536.</ref>.

==Article abstract==
Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.

=Implications=
This research helps to define the role of NAD+ and NMN in the pathogenesis of diabetes. It underscores that decline in NAD+ and the resulting metabolic complications of diabetes may be effectively reversed by NMN supplementation. Additionally, the research found that the mechanism by which NMN improves the diabetic phenotype may be different in male and female mice. While further research is needed to confirm these findings and define the sex-specific changes, this work lays the groundwork for that research.

==Additional research to be conducted==
The authors note that the natural extension of their work would be to attempt to replicate the preliminary results in human trials. Specifically, understanding the changes in NAD+ associated with T2D in humans, as well as the potential role for NMN supplementation. Additionally, they note that future work should focus on investigating the potential for a combination intervention of NMN supplementation with sirtuin-1 activators because of the potential for synergistic improvement in metabolism.

==Institution==
[[Shin-ichiro Imai|Dr. Shin-ichiro Imai]]'s lab has been an active contributor to the body of literature investigating NMN and its potential benefits. His lab at [[Washington University]] in St. Louis has produced several other manuscripts investigating the role of sirtuins in longevity and insulin sensitivity as well as the metabolism of NAD+<ref>Luo J, Nikolaev AY, Imai S ichiro, et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001;107(2):137-148.</ref><ref>Revollo JR, Grimm AA, Imai SI. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004;279(49):50754-50763.</ref><ref>Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005;2(2):105-117.</ref>.

==Funding==
This work was supported by the National Institute on Aging (AG02150), the Ellison Medical Foundation, and the Longer Life Foundation to S.I. and by institutional support from the Washington University Nutrition Obesity Research Center (P30DK056341) and the Washington University Diabetes Research and Training Center (P60DK020579). The authors reported individual funding of financial interests with the following: Japan Research Foundation for Clinical Pharmacology, the Manpei Suzuki Diabetes Foundation, the Kanae Foundation For the Promotion of Medical Science, and Sirtris, a GSK company.

==Authors/ Researchers==

*Jun Yoshino – Department of Developmental Biology, Washington University of St. Louis
*Kathryn F Mills – Department of Developmental Biology, Washington University of St. Louis
*Myeong Jin Yoon - Department of Developmental Biology, Washington University of St. Louis
*[[Shin-ichiro Imai|Dr. Shin-ichiro Imai]] - Department of Developmental Biology, Washington University of St. Louis

==References==
[[Category:Research]]
<references />
[[Category:Full index]]

Nicotinamide mononucleotide , a key NAD+ intermediate , treats the pathophysiology of diet- and age- induced diabetes in mice

2020-06-11T20:04:13Z

JW008:

'''Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice''' In this study, Yoshino et al. investigated the role of NMN in an animal model of type 2 diabetes (T2D). The authors induced T2D with a high-fat diet, and then administered 500 mg / kg of NMN over 7 or 10 days. The authors found that in untreated mice with T2D, NAD+ biosynthesis was severely diminished in white adipose tissue (WAT) and hepatocytes. Following NMN administration, the authors observed at 15x increase in intracellular NMN, as well as a 5x increase in hepatocyte nicotinamide riboside (NR). The authors also found that NMN supplementation improved insulin-response in T2D mice, in females by improving insulin sensitivity, while in males by improving glucose-stimulated insulin secretion. They were unsure of the exact reason for gender-specific responses to NMN. They also found that Sirtuin 1 was one of the mediators of the improvements associated with NMN, and that treatment with NMN also improved metabolic complications of T2D in these mice<ref>Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536.</ref>.

==Article abstract==
Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.

=Implications=
This research helps to define the role of NAD+ and NMN in the pathogenesis of diabetes. It underscores that decline in NAD+ and the resulting metabolic complications of diabetes may be effectively reversed by NMN supplementation. Additionally, the research found that the mechanism by which NMN improves the diabetic phenotype may be different in male and female mice. While further research is needed to confirm these findings and define the sex-specific changes, this work lays the groundwork for that research.

==Additional research to be conducted==
The authors note that the natural extension of their work would be to attempt to replicate the preliminary results in human trials. Specifically, understanding the changes in NAD+ associated with T2D in humans, as well as the potential role for NMN supplementation. Additionally, they note that future work should focus on investigating the potential for a combination intervention of NMN supplementation with sirtuin-1 activators because of the potential for synergistic improvement in metabolism.

==Institution==
Dr. [[Shin-ichiro Imai|Dr. Shin-ichiro Imai]]'s lab has been an active contributor to the body of literature investigating NMN and its potential benefits. His lab at [[Washington University]] in St. Louis has produced several other manuscripts investigating the role of sirtuins in longevity and insulin sensitivity as well as the metabolism of NAD+<ref>Luo J, Nikolaev AY, Imai S ichiro, et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001;107(2):137-148.</ref><ref>Revollo JR, Grimm AA, Imai SI. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004;279(49):50754-50763.</ref><ref>Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005;2(2):105-117.</ref>.

==Funding==
This work was supported by the National Institute on Aging (AG02150), the Ellison Medical Foundation, and the Longer Life Foundation to S.I. and by institutional support from the Washington University Nutrition Obesity Research Center (P30DK056341) and the Washington University Diabetes Research and Training Center (P60DK020579). The authors reported individual funding of financial interests with the following: Japan Research Foundation for Clinical Pharmacology, the Manpei Suzuki Diabetes Foundation, the Kanae Foundation For the Promotion of Medical Science, and Sirtris, a GSK company.

==Authors/ Researchers==

*Jun Yoshino – Department of Developmental Biology, Washington University of St. Louis
*Kathryn F Mills – Department of Developmental Biology, Washington University of St. Louis
*Myeong Jin Yoon - Department of Developmental Biology, Washington University of St. Louis
*[[Shin-ichiro Imai|Dr. Shin-ichiro Imai]] - Department of Developmental Biology, Washington University of St. Louis

==References==
[[Category:Research]]
<references />
[[Category:Full index]]

Nicotinamide mononucleotide , a key NAD+ intermediate , treats the pathophysiology of diet- and age- induced diabetes in mice

2020-06-11T20:03:42Z

JW008: /* Authors/ Researchers */

'''Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice''' In this study, Yoshino et al. investigated the role of NMN in an animal model of type 2 diabetes (T2D). The authors induced T2D with a high-fat diet, and then administered 500 mg / kg of NMN over 7 or 10 days. The authors found that in untreated mice with T2D, NAD+ biosynthesis was severely diminished in white adipose tissue (WAT) and hepatocytes. Following NMN administration, the authors observed at 15x increase in intracellular NMN, as well as a 5x increase in hepatocyte nicotinamide riboside (NR). The authors also found that NMN supplementation improved insulin-response in T2D mice, in females by improving insulin sensitivity, while in males by improving glucose-stimulated insulin secretion. They were unsure of the exact reason for gender-specific responses to NMN. They also found that Sirtuin 1 was one of the mediators of the improvements associated with NMN, and that treatment with NMN also improved metabolic complications of T2D in these mice<ref>Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536.</ref>.

==Article abstract==
Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.

=Implications=
This research helps to define the role of NAD+ and NMN in the pathogenesis of diabetes. It underscores that decline in NAD+ and the resulting metabolic complications of diabetes may be effectively reversed by NMN supplementation. Additionally, the research found that the mechanism by which NMN improves the diabetic phenotype may be different in male and female mice. While further research is needed to confirm these findings and define the sex-specific changes, this work lays the groundwork for that research.

==Additional research to be conducted==
The authors note that the natural extension of their work would be to attempt to replicate the preliminary results in human trials. Specifically, understanding the changes in NAD+ associated with T2D in humans, as well as the potential role for NMN supplementation. Additionally, they note that future work should focus on investigating the potential for a combination intervention of NMN supplementation with sirtuin-1 activators because of the potential for synergistic improvement in metabolism.

==Institution==
Dr. Imai’s lab has been an active contributor to the body of literature investigating NMN and its potential benefits. His lab at Washington University in St. Louis has produced several other manuscripts investigating the role of sirtuins in longevity and insulin sensitivity as well as the metabolism of NAD+<ref>Luo J, Nikolaev AY, Imai S ichiro, et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001;107(2):137-148.</ref><ref>Revollo JR, Grimm AA, Imai SI. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004;279(49):50754-50763.</ref><ref>Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005;2(2):105-117.</ref>.

==Funding==
This work was supported by the National Institute on Aging (AG02150), the Ellison Medical Foundation, and the Longer Life Foundation to S.I. and by institutional support from the Washington University Nutrition Obesity Research Center (P30DK056341) and the Washington University Diabetes Research and Training Center (P60DK020579). The authors reported individual funding of financial interests with the following: Japan Research Foundation for Clinical Pharmacology, the Manpei Suzuki Diabetes Foundation, the Kanae Foundation For the Promotion of Medical Science, and Sirtris, a GSK company.

==Authors/ Researchers==

*Jun Yoshino – Department of Developmental Biology, Washington University of St. Louis
*Kathryn F Mills – Department of Developmental Biology, Washington University of St. Louis
*Myeong Jin Yoon - Department of Developmental Biology, Washington University of St. Louis
*[[Shin-ichiro Imai|Dr. Shin-ichiro Imai]] - Department of Developmental Biology, Washington University of St. Louis

==References==
[[Category:Research]]
<references />
[[Category:Full index]]

Washington University

2020-06-11T20:02:38Z

JW008: Created page with "Washington University in St. Louis is a private research university located in St. Louis, Missouri. ==Published Research Articles== Long-term administration of nicotinamide..."

Washington University in St. Louis is a private research university located in St. Louis, Missouri.

==Published Research Articles==
[[Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice]]

==Notable Figures in NMN Research==
*[[Shin-ichiro Imai|Dr. Shin-ichiro Imai]]

[[Category:Institutions]]
[[Category:Full index]]

Harvard

2020-06-11T19:59:12Z

JW008: Created page with "Harvard Medical School (HMS) is the medical school and medical science research wing of Harvard University. The medical school was founded in 1782 and is considered a leader i..."

Harvard Medical School (HMS) is the medical school and medical science research wing of Harvard University. The medical school was founded in 1782 and is considered a leader in the United States for basic science and translational medical research.

==Published Research Articles==
[[Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice]]

==Notable Figures in NMN Research==
*[[David Sinclair]]

[[Category:Institutions]]
[[Category:Full index]]

Nicotinamide mononucleotide , a key NAD+ intermediate , treats the pathophysiology of diet- and age- induced diabetes in mice

2020-06-11T19:50:50Z

JW008:

'''Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice''' In this study, Yoshino et al. investigated the role of NMN in an animal model of type 2 diabetes (T2D). The authors induced T2D with a high-fat diet, and then administered 500 mg / kg of NMN over 7 or 10 days. The authors found that in untreated mice with T2D, NAD+ biosynthesis was severely diminished in white adipose tissue (WAT) and hepatocytes. Following NMN administration, the authors observed at 15x increase in intracellular NMN, as well as a 5x increase in hepatocyte nicotinamide riboside (NR). The authors also found that NMN supplementation improved insulin-response in T2D mice, in females by improving insulin sensitivity, while in males by improving glucose-stimulated insulin secretion. They were unsure of the exact reason for gender-specific responses to NMN. They also found that Sirtuin 1 was one of the mediators of the improvements associated with NMN, and that treatment with NMN also improved metabolic complications of T2D in these mice<ref>Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536.</ref>.

==Article abstract==
Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.

=Implications=
This research helps to define the role of NAD+ and NMN in the pathogenesis of diabetes. It underscores that decline in NAD+ and the resulting metabolic complications of diabetes may be effectively reversed by NMN supplementation. Additionally, the research found that the mechanism by which NMN improves the diabetic phenotype may be different in male and female mice. While further research is needed to confirm these findings and define the sex-specific changes, this work lays the groundwork for that research.

==Additional research to be conducted==
The authors note that the natural extension of their work would be to attempt to replicate the preliminary results in human trials. Specifically, understanding the changes in NAD+ associated with T2D in humans, as well as the potential role for NMN supplementation. Additionally, they note that future work should focus on investigating the potential for a combination intervention of NMN supplementation with sirtuin-1 activators because of the potential for synergistic improvement in metabolism.

==Institution==
Dr. Imai’s lab has been an active contributor to the body of literature investigating NMN and its potential benefits. His lab at Washington University in St. Louis has produced several other manuscripts investigating the role of sirtuins in longevity and insulin sensitivity as well as the metabolism of NAD+<ref>Luo J, Nikolaev AY, Imai S ichiro, et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001;107(2):137-148.</ref><ref>Revollo JR, Grimm AA, Imai SI. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004;279(49):50754-50763.</ref><ref>Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005;2(2):105-117.</ref>.

==Funding==
This work was supported by the National Institute on Aging (AG02150), the Ellison Medical Foundation, and the Longer Life Foundation to S.I. and by institutional support from the Washington University Nutrition Obesity Research Center (P30DK056341) and the Washington University Diabetes Research and Training Center (P60DK020579). The authors reported individual funding of financial interests with the following: Japan Research Foundation for Clinical Pharmacology, the Manpei Suzuki Diabetes Foundation, the Kanae Foundation For the Promotion of Medical Science, and Sirtris, a GSK company.

==Authors/ Researchers==

*Jun Yoshino – Department of Developmental Biology, Washington University of St. Louis
*Kathryn F Mills – Department of Developmental Biology, Washington University of St. Louis
*Myeong Jin Yoon - Department of Developmental Biology, Washington University of St. Louis
*Shin-Ichiro Imai - Department of Developmental Biology, Washington University of St. Louis

==References==
[[Category:Research]]
<references />
[[Category:Full index]]

Nicotinamide mononucleotide , a key NAD+ intermediate , treats the pathophysiology of diet- and age- induced diabetes in mice

2020-06-11T19:50:38Z

JW008: Created page with "'''Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice'''In this study, Yoshino et al. investigated the..."

'''Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice'''In this study, Yoshino et al. investigated the role of NMN in an animal model of type 2 diabetes (T2D). The authors induced T2D with a high-fat diet, and then administered 500 mg / kg of NMN over 7 or 10 days. The authors found that in untreated mice with T2D, NAD+ biosynthesis was severely diminished in white adipose tissue (WAT) and hepatocytes. Following NMN administration, the authors observed at 15x increase in intracellular NMN, as well as a 5x increase in hepatocyte nicotinamide riboside (NR). The authors also found that NMN supplementation improved insulin-response in T2D mice, in females by improving insulin sensitivity, while in males by improving glucose-stimulated insulin secretion. They were unsure of the exact reason for gender-specific responses to NMN. They also found that Sirtuin 1 was one of the mediators of the improvements associated with NMN, and that treatment with NMN also improved metabolic complications of T2D in these mice<ref>Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536.</ref>.

==Article abstract==
Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.

=Implications=
This research helps to define the role of NAD+ and NMN in the pathogenesis of diabetes. It underscores that decline in NAD+ and the resulting metabolic complications of diabetes may be effectively reversed by NMN supplementation. Additionally, the research found that the mechanism by which NMN improves the diabetic phenotype may be different in male and female mice. While further research is needed to confirm these findings and define the sex-specific changes, this work lays the groundwork for that research.

==Additional research to be conducted==
The authors note that the natural extension of their work would be to attempt to replicate the preliminary results in human trials. Specifically, understanding the changes in NAD+ associated with T2D in humans, as well as the potential role for NMN supplementation. Additionally, they note that future work should focus on investigating the potential for a combination intervention of NMN supplementation with sirtuin-1 activators because of the potential for synergistic improvement in metabolism.

==Institution==
Dr. Imai’s lab has been an active contributor to the body of literature investigating NMN and its potential benefits. His lab at Washington University in St. Louis has produced several other manuscripts investigating the role of sirtuins in longevity and insulin sensitivity as well as the metabolism of NAD+<ref>Luo J, Nikolaev AY, Imai S ichiro, et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001;107(2):137-148.</ref><ref>Revollo JR, Grimm AA, Imai SI. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004;279(49):50754-50763.</ref><ref>Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005;2(2):105-117.</ref>.

==Funding==
This work was supported by the National Institute on Aging (AG02150), the Ellison Medical Foundation, and the Longer Life Foundation to S.I. and by institutional support from the Washington University Nutrition Obesity Research Center (P30DK056341) and the Washington University Diabetes Research and Training Center (P60DK020579). The authors reported individual funding of financial interests with the following: Japan Research Foundation for Clinical Pharmacology, the Manpei Suzuki Diabetes Foundation, the Kanae Foundation For the Promotion of Medical Science, and Sirtris, a GSK company.

==Authors/ Researchers==

*Jun Yoshino – Department of Developmental Biology, Washington University of St. Louis
*Kathryn F Mills – Department of Developmental Biology, Washington University of St. Louis
*Myeong Jin Yoon - Department of Developmental Biology, Washington University of St. Louis
*Shin-Ichiro Imai - Department of Developmental Biology, Washington University of St. Louis

==References==
[[Category:Research]]
<references />
[[Category:Full index]]

Head to head comparison of short term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide(NMN) and 6 weeks of exercise in obese female mice

2020-06-11T19:44:05Z

JW008:

This study compared the changes associated with NMN or exercise interventions in mice. The 60 mice were separated into 5 groups: chow sedentary, chow exercise, high-fat diet (HFD) sedentary, HFT with NMN, and HFT with exercise. After 6 weeks of diet, the animals in the exercise intervention began 6 weeks of 6 day / week exercise regimen. Mice in the NMN group received 500 mg/kg NMN intra-peritoneally for the last 17 days of the study. Following 6 weeks of their respective diets, the mice in the HFD group were 23% heavier than the chow-fed mice. In the HFD mice, the authors found that both NMN and exercise improved insulin sensitivity, as evidenced by the area under the curve of a glucose vs. time graph following feeding (p < 0.05 for both compared to HFD sedentary). Additionally, the authors found that HFD was associated with lower NAD+ in liver and skeletal muscle tissues and that NMN treatment increased NAD+ levels in both tissues, whereas exercise only significantly increased NAD+ in muscle tissue. In addition, citrate synthase, an enzyme which is associated with mitochondrial activity, was reduced in muscle and liver in mice on the HFD. Exercise resulted in significant increases in citrate synthase activity in skeletal muscle while NMN supplementation did not, and NMN supplementation and exercise both resulted in increased activity in liver tissue<ref>Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Front Pharmacol. 2016;7(AUG)</ref>.

== Article Abstract ==
Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD(+) levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD(+) only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

== Implications ==
This article highlighted not only the pathology associated with high-fat diet (HFD), but also the potential utility of NMN in addressing this pathology. Specifically, this research showed that both exercise and NMN supplementation were effective in addressing some of the changes that resulted from HFD; however, there appeared to be tissue-specific differences in these effects. This is important, because NMN tended to exert more change in the liver, whereas the benefits from exercise were seen primarily in the muscle tissue. This could mean that NMN may be effective in reversing some of the more systemic negative effects of HFD such as fatty liver.

== Additional Research to be Conducted ==
Future work will likely continue to build upon the findings made in this report – that NMN and exercise exert different effects on different tissues. The authors of this study note that their future work may focus on identifying exactly why NMN supplementation seems to affect liver mitochondrial function whereas exercise’s effects on mitochondria seem specific to skeletal muscle.

== Institution ==
Dr. Morris’ lab is located at the University of New South Wales. Her group has published several other papers investigating the potential applications of NMN to improve obesity-related disease as well as male and female reproductive health<ref>Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: Comparison with exercise. Sci Rep. 2017;7(1)</ref><ref>Uddin GM, Youngson NA, Chowdhury SS, Hagan C, Sinclair DA, Morris MJ. Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers. Cells. 2020;9(4):791.</ref><ref>Youngson NA, Mezbah Uddin G, Das A, et al. Impacts of obesity, maternal obesity and nicotinamide mononucleotide supplementation on sperm quality in mice. Reproduction. 2019;158(2):169-179.</ref>.

== Funding ==
This research was funded by the National Health and Medical Research Council (NHMRC).

== Authors/Researchers ==
*Golam Uddin – Department of Pharmacology, University of New South Wales
*Neil Youngson - Department of Pharmacology, University of New South Wales
*[[David Sinclair]] – Department of Genetics, Harvard Medical School
*Margaret Morris - Department of Pharmacology, University of New South Wales

== References ==
[[Category:Research]]
<references />
[[Category:Full index]]

Head to head comparison of short term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide(NMN) and 6 weeks of exercise in obese female mice

2020-06-11T19:43:18Z

JW008: /* Authors/Researchers */

This study compared the changes associated with NMN or exercise interventions in mice. The 60 mice were separated into 5 groups: chow sedentary, chow exercise, high-fat diet (HFD) sedentary, HFT with NMN, and HFT with exercise. After 6 weeks of diet, the animals in the exercise intervention began 6 weeks of 6 day / week exercise regimen. Mice in the NMN group received 500 mg/kg NMN intra-peritoneally for the last 17 days of the study. Following 6 weeks of their respective diets, the mice in the HFD group were 23% heavier than the chow-fed mice. In the HFD mice, the authors found that both NMN and exercise improved insulin sensitivity, as evidenced by the area under the curve of a glucose vs. time graph following feeding (p < 0.05 for both compared to HFD sedentary). Additionally, the authors found that HFD was associated with lower NAD+ in liver and skeletal muscle tissues and that NMN treatment increased NAD+ levels in both tissues, whereas exercise only significantly increased NAD+ in muscle tissue. In addition, citrate synthase, an enzyme which is associated with mitochondrial activity, was reduced in muscle and liver in mice on the HFD. Exercise resulted in significant increases in citrate synthase activity in skeletal muscle while NMN supplementation did not, and NMN supplementation and exercise both resulted in increased activity in liver tissue<ref>Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Front Pharmacol. 2016;7(AUG)</ref>.

== Article Abstract ==
Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD(+) levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD(+) only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

== Implications ==
This article highlighted not only the pathology associated with high-fat diet (HFD), but also the potential utility of NMN in addressing this pathology. Specifically, this research showed that both exercise and NMN supplementation were effective in addressing some of the changes that resulted from HFD; however, there appeared to be tissue-specific differences in these effects. This is important, because NMN tended to exert more change in the liver, whereas the benefits from exercise were seen primarily in the muscle tissue. This could mean that NMN may be effective in reversing some of the more systemic negative effects of HFD such as fatty liver.

== Additional Research to be Conducted ==
Future work will likely continue to build upon the findings made in this report – that NMN and exercise exert different effects on different tissues. The authors of this study note that their future work may focus on identifying exactly why NMN supplementation seems to affect liver mitochondrial function whereas exercise’s effects on mitochondria seem specific to skeletal muscle.

== Institution ==
Dr. Morris’ lab is located at the University of New South Wales. Her group has published several other papers investigating the potential applications of NMN to improve obesity-related disease as well as male and female reproductive health<ref>Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: Comparison with exercise. Sci Rep. 2017;7(1)</ref><ref>Uddin GM, Youngson NA, Chowdhury SS, Hagan C, Sinclair DA, Morris MJ. Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers. Cells. 2020;9(4):791.</ref><ref>Youngson NA, Mezbah Uddin G, Das A, et al. Impacts of obesity, maternal obesity and nicotinamide mononucleotide supplementation on sperm quality in mice. Reproduction. 2019;158(2):169-179.</ref>.

== Funding ==
This research was funded by the National Health and Medical Research Council (NHMRC).

== Authors/Researchers ==
*Golam Uddin – Department of Pharmacology, University of New South Wales
*Neil Youngson - Department of Pharmacology, University of New South Wales
*David Sinclair – Department of Genetics, Harvard Medical School
*Margaret Morris - Department of Pharmacology, University of New South Wales

== References ==
[[Category:Research]]
<references />
[[Category:Full index]]

Head to head comparison of short term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide(NMN) and 6 weeks of exercise in obese female mice

2020-06-11T19:42:23Z

JW008: Created page with "This study compared the changes associated with NMN or exercise interventions in mice. The 60 mice were separated into 5 groups: chow sedentary, chow exercise, high-fat diet (..."

This study compared the changes associated with NMN or exercise interventions in mice. The 60 mice were separated into 5 groups: chow sedentary, chow exercise, high-fat diet (HFD) sedentary, HFT with NMN, and HFT with exercise. After 6 weeks of diet, the animals in the exercise intervention began 6 weeks of 6 day / week exercise regimen. Mice in the NMN group received 500 mg/kg NMN intra-peritoneally for the last 17 days of the study. Following 6 weeks of their respective diets, the mice in the HFD group were 23% heavier than the chow-fed mice. In the HFD mice, the authors found that both NMN and exercise improved insulin sensitivity, as evidenced by the area under the curve of a glucose vs. time graph following feeding (p < 0.05 for both compared to HFD sedentary). Additionally, the authors found that HFD was associated with lower NAD+ in liver and skeletal muscle tissues and that NMN treatment increased NAD+ levels in both tissues, whereas exercise only significantly increased NAD+ in muscle tissue. In addition, citrate synthase, an enzyme which is associated with mitochondrial activity, was reduced in muscle and liver in mice on the HFD. Exercise resulted in significant increases in citrate synthase activity in skeletal muscle while NMN supplementation did not, and NMN supplementation and exercise both resulted in increased activity in liver tissue<ref>Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Front Pharmacol. 2016;7(AUG)</ref>.

== Article Abstract ==
Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD(+) levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD(+) only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

== Implications ==
This article highlighted not only the pathology associated with high-fat diet (HFD), but also the potential utility of NMN in addressing this pathology. Specifically, this research showed that both exercise and NMN supplementation were effective in addressing some of the changes that resulted from HFD; however, there appeared to be tissue-specific differences in these effects. This is important, because NMN tended to exert more change in the liver, whereas the benefits from exercise were seen primarily in the muscle tissue. This could mean that NMN may be effective in reversing some of the more systemic negative effects of HFD such as fatty liver.

== Additional Research to be Conducted ==
Future work will likely continue to build upon the findings made in this report – that NMN and exercise exert different effects on different tissues. The authors of this study note that their future work may focus on identifying exactly why NMN supplementation seems to affect liver mitochondrial function whereas exercise’s effects on mitochondria seem specific to skeletal muscle.

== Institution ==
Dr. Morris’ lab is located at the University of New South Wales. Her group has published several other papers investigating the potential applications of NMN to improve obesity-related disease as well as male and female reproductive health<ref>Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: Comparison with exercise. Sci Rep. 2017;7(1)</ref><ref>Uddin GM, Youngson NA, Chowdhury SS, Hagan C, Sinclair DA, Morris MJ. Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers. Cells. 2020;9(4):791.</ref><ref>Youngson NA, Mezbah Uddin G, Das A, et al. Impacts of obesity, maternal obesity and nicotinamide mononucleotide supplementation on sperm quality in mice. Reproduction. 2019;158(2):169-179.</ref>.

== Funding ==
This research was funded by the National Health and Medical Research Council (NHMRC).

== Authors/Researchers ==
Golam Uddin – Department of Pharmacology, University of New South Wales
Neil Youngson - Department of Pharmacology, University of New South Wales
David Sinclair – Department of Genetics, Harvard Medical School
Margaret Morris - Department of Pharmacology, University of New South Wales

== References ==
[[Category:Research]]
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