Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice
Open accessAbstract
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.
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NMN enhances mitochondrial function in various organs, including skeletal muscle, kidney, liver, heart, eyes, brain and the cardiovascular system, and can mitigate oxidative stress in the vasculature, including improvements in neurovascular coupling responses in the aged cortex.
“NMN enhances mitochondrial function in various organs, including skeletal muscle201, kidney202–204, liver203, heart205, eyes206, brain161 and the cardiovascular system207, and can mitigate oxidative stress in the vasculature208, including improvements in neurovascular coupling responses in the aged cortex of the brain209.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [203]
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Turner, N., Bruce, C. R., Beale, S. M., Hoehn, K. L., So, T., Rolph, M. S., & Cooney, G. J. (2007) · Diabetes · doi:10.2337/db07-0093 · Cited by 520 · cited 1× · see citing works
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MethodTargeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
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Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis
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“7:258. doi: 10.3389/fphar.2016.00258 Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice Golam M. Uddin1†, Neil A. Youngson1†, David A. Sinclair1,2 and Margaret J. Morris1* 1 Department of Pharmacology, School of Medical…”
BackgroundInfluentialSelf-citationExercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats
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Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · cited 1× · see citing works
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“Furthermore recent studies on maternal obesity have revealed the alarming metabolic impact on offspring, including increased risk for obesity (Borengasser et al., 2014; Catalano, 2015; Raipuria et al., 2015), highlighting the importance of testing interventions in obese females.”
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“If this is the case, then the NAD+stimulated fat metabolism pathways (Han et al., 2010; Ponugoti et al., 2010) may be more clinically important than NAD+stimulated mitochondrial biogenesis (Wu et al., 1999; Nemoto et al., 2004) pathways in liver.”
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“A variety of human and animal studies have suggested that exercise can exert health benefits in obesity (Christ et al., 2002; Flores et al., 2006; Vieira et al., 2009; Ross et al., 2015).”
BackgroundNAD+/NADH and skeletal muscle mitochondrial adaptations to exercise
White, A. T., & Schenk, S. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00054.2012 · Cited by 193 · cited 8× · see citing works
“Frontiers in Pharmacology | www.frontiersin.org 7 August 2016 | Volume 7 | Article 258 FIGURE 5 | Citrate synthase (µ mol/mg protein) and mtDNA copy (arbitrary number) in quadriceps muscle (A,C) and liver (B,D) of CS, CEX, HS, HNMN, and HEX mice.”
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“A variety of human and animal studies have suggested that exercise can exert health benefits in obesity (Christ et al., 2002; Flores et al., 2006; Vieira et al., 2009; Ross et al., 2015).”
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“Consequently interventions that alter mitochondrial biogenesis or function have been proposed as an option for combatting obesity-related disease (Joseph et al., 2011; Holmström et al., 2012).”
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“Consequently interventions that alter mitochondrial biogenesis or function have been proposed as an option for combatting obesity-related disease (Joseph et al., 2011; Holmström et al., 2012).”
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“Furthermore recent studies on maternal obesity have revealed the alarming metabolic impact on offspring, including increased risk for obesity (Borengasser et al., 2014; Catalano, 2015; Raipuria et al., 2015), highlighting the importance of testing interventions in obese females.”
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“In quadriceps muscle the HEX groups showed effects that were consistent with long-term exercise (Brandauer et al., 2013; Yuan et al., 2014).”
BackgroundLima, F. D., Stamm, D. N., Della-Pace, I. D., Dobrachinski, F., de Carvalho, N. R., Royes, L. F. F., Soares, F. A. A., da Rocha, J. B. T., González‐Gallego, J., & Bresciani, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055668 · Cited by 99 · cited 1× · see citing works
“…may stimulate mitochondrial function though saturating the cell with an oxidizing agent (NAD+), or through stimulating sirtuin mediated pathways (Kim ref), while the effects of exercise on liver mitochondria may be more regulated by signalzing from muscles or the brain (Lima et al., 2013).”
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“A variety of human and animal studies have suggested that exercise can exert health benefits in obesity (Christ et al., 2002; Flores et al., 2006; Vieira et al., 2009; Ross et al., 2015).”
BackgroundMelatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats
Agil, A., El‐Hammadi, M. M., Jiménez‐Aranda, A., Tassi, M., Abdo, W. S., Fernández‐Vázquez, G., & Reiter, R. J. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12241 · Cited by 88 · cited 2× · see citing works
“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).”
BackgroundMethodImpact of Various Exercise Modalities on Hepatic Mitochondrial Function
Fletcher, J. A., Meers, G. M.-E., Linden, M. A., Kearney, M. L., Morris, E. M., Thyfault, J. P., & Rector, R. S. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000223 · Cited by 69 · see citing works
Effect of exercise on mouse liver and brain bioenergetic infrastructures
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“The exercise effects in liver in the HEX compared to the HS group were consistent with those seen with longterm exercise (Goncalves et al., 2013).”
ResultAdolescents' Perception of Causes of Obesity: Unhealthy Lifestyles or Heritage?
Gonçalves, H., González‐Chica, D. A., Araújo, C. L., Muniz, L. C., Tavares, P., Assunção, M. C. F., Menezes, A. M. B., & Hallal, P. C. (2012) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2012.08.015 · Cited by 34 · cited 2× · see citing works
“…17 June 2016 Accepted: 02 August 2016 Published: 19 August 2016 Citation: Uddin GM, Youngson NA, Sinclair DA and Morris MJ (2016) Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice.”
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“At 18 weeks of age, after 5 h fasting, mice were deeply anesthetized (ketamine/xylazine 200/20 mg/kg, i.p.).”
MethodExercise increases the binding of MEF 2A to the Cpt1b promoter in mouse skeletal muscle
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“Exercise increases the rates of lipolysis and fat oxidation (Turner et al., 2014) and accordingly exercise training in obese rodents has been shown to increase lipid metabolism and mitochondrial biogenesis in muscle (Suga et al., 2013; Kwon et al., 2014).”
BackgroundKwon, S. M., Park, H. G., Jun, J. K., & Lee, W. L. (2014) · Physical Activity and Nutrition · doi:10.5717/jenb.2014.18.1.51 · Cited by 21 · cited 1× · see citing works
“Exercise increases the rates of lipolysis and fat oxidation (Turner et al., 2014) and accordingly exercise training in obese rodents has been shown to increase lipid metabolism and mitochondrial biogenesis in muscle (Suga et al., 2013; Kwon et al., 2014).”
BackgroundOverexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance
Brandon, A. E., Tid-Ang, J. D., Wright, L. E., Stuart, E., Suryana, E., Bentley, N. L., Turner, N. A., Cooney, G. J., Ruderman, N. B., & Kraegen, E. W. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121959 · Cited by 18 · cited 1× · see citing works
“Protein was extracted as described previously Brandon et al. (2015).”
Maternal obesity regulates gene expression in the hearts of offspring
Raipuria, M., Hardy, G., Bahari, H., & Morris, M. J. (2015) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2015.05.011 · Cited by 16 · cited 4× · see citing works
“Furthermore recent studies on maternal obesity have revealed the alarming metabolic impact on offspring, including increased risk for obesity (Borengasser et al., 2014; Catalano, 2015; Raipuria et al., 2015), highlighting the importance of testing interventions in obese females.”
BackgroundInfluentialSelf-citationGariani, K., Menzies, K. J., Ryu, D., Wegner, C. J., Wang, X., Ropelle, E. R., Moullan, N., Zhang, H., Perino, A., Lemos, V., et al. (2015) · doi:10.7892/boris.75642 · Cited by 7 · see citing works
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NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
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“Interestingly, recent studies have documented both at micromolar concentrations in human and cow milk (Bieganowski and Brenner, 2004; Ummarino et al., 2017).”
Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496 · see citing works
“Alternatively, NAD levels in muscle and liver weremeasured by assay in-house developedmethod (Uddin et al., 2016).”
Self-citationNAD(+) in aging: molecular mechanisms and translational implications
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.001 · Cited by 501 · see citing works
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S.-I., et al. (2021) · Science · doi:10.1126/science.abe9985 · Cited by 439 · see citing works
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NAD metabolism: Implications in aging and longevity
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Implications of altered NAD metabolism in metabolic disorders
Okabe, K., Yaku, K., Tobe, K., & Nakagawa, T. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0527-8 · Cited by 223 · see citing works
“NMN 500mg/kg Liver↑, Skeletal muscle↑ Improved glucose tolerance, liver citrate synthase activity, and triglyceride accumulation [64]”
Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns
Nadeeshani, H., Li, J., Ying, T., Zhang, B., & Lu, J. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.08.003 · Cited by 213 · see citing works
“However, contradictory results have been reported with NMN supplementation as it reduced adiposity and enhanced insulin sensitivity [24,72].”
BackgroundHong, W., Mo, F., Zhang, Z., Huang, M., & Wei, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00246 · Cited by 179 · see citing works
“Exercises and NMN have a similar effect on glucose intolerance induced by obesity, however, these two interventions are tissue-specific with a different impact on mitochondrial function in muscles and the liver (Uddin et al., 2016).”
BackgroundWang, S., Wan, T., Ye, M., Qiu, Y., Pei, L., Jiang, R., Pang, N., Huang, Y., Liang, B., Ling, W., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.04.006 · Cited by 174 · see citing works
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“…of boosting NAD+ metabolism, including NMN supplementation and pharmacological inhibition of the NAD+-consuming PARP1 enzyme (Bai et al. 2011; Pirinen et al. 2014), ameliorate mitochondrial dysfunction in the skeletal muscle of mice (Gomes et al. 2013; Mills et al. 2016; Uddin et al. 2016).”
BackgroundNicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule
Poddar, S. K., Sifat, A. E., Haque, S., Nahid, N. A., Chowdhury, S., & Mehedi, I. (2019) · Biomolecules · doi:10.3390/biom9010034 · Cited by 136 · see citing works
The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update
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ER stress-induced upregulation of NNMT contributes to alcohol-related fatty liver development
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Emerging role of aging in the progression of NAFLD to HCC
He, Y., Su, Y., Duan, C., Wang, S., He, W. G., Zhang, Y., An, X., & He, M. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101833 · Cited by 98 · see citing works
NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis
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“Recent studies in humans demonstrate that NR supplementation reduces the levels of circulating inflammatory cytokines [98] , while Nicotinamide Mononucleotide (NMN) may reduce the expression of these cytokines [99] .”
BackgroundRole of endothelial NAD+deficiency in age-related vascular dysfunction
Csiszár, A., Tarantini, S., Yabluchanskiy, A., Balasubramanian, P., Kiss, T., Farkas, E., Baur, J. A., & Ungvari, Z. I. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00039.2019 · Cited by 93 · see citing works
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“In previous studies, NMN was administered to mice at doses of ~100 mg·kg 1 (Park et al., 2016) to 500 mg·kg 1 (Long et al., 2015; Uddin et al., 2016).”
BackgroundMethodUddin, G. M., Youngson, N. A., Doyle, B. M., Sinclair, D. A., & Morris, M. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-14866-z · Cited by 82 · see citing works
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The therapeutic perspective of NAD+ precursors in age-related diseases
Iqbal, T., & Nakagawa, T. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149590 · Cited by 65 · see citing works
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NAD+ Deficits in Age-Related Diseases and Cancer
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Roles of NAD + in Health and AgingPreprint
Lautrup, S., Hou, Y., Fang, E. F., & Bohr, V. A. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041193 · Cited by 53 · see citing works
Deletion of BCATm increases insulin-stimulated glucose oxidation in the heart
Uddin, G. M., Karwi, Q. G., Pherwani, S., Gopal, K., Wagg, C. S., Biswas, D., Atnasious, M., Wu, Y., Wu, G., Zhang, L., et al. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154871 · Cited by 47 · see citing works
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“The optimal oral dosage of NMN for mice is generally 300e500 mg/kg per day (Spinnler et al., 2013; Mills et al., 2016; Uddin et al., 2016, 2017; Xie et al., 2020a).”
BackgroundNicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns
Bhasin, S., Seals, D. R., Migaud, M. E., Musi, N., & Baur, J. A. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad019 · Cited by 47 · see citing works
Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise
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The emergence of the nicotinamide riboside kinases in the regulation of NAD+ metabolism
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Mitochondrial function in liver cells is resistant to perturbations in NAD+ salvage capacity
Dall, M., Trammell, S. A. J., Asping, M., Hassing, A. S., Agerholm, M., Vienberg, S. G., Gillum, M. P., Larsen, S., & Treebak, J. T. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006756 · Cited by 40 · see citing works
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“All steps apart from the filtering of lysate through a column were performed as previously described (Uddin et al. 2016).”
InfluentialSelf-citationNicotinamide protects against skeletal muscle atrophy in streptozotocin-induced diabetic mice
Guo, S., Chen, Q., Sun, Y., & Chen, J. (2019) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2019.1638414 · Cited by 37 · see citing works
Systematic Review and Meta-Analysis of Endurance Exercise Training Protocols for Mice
Massett, M. P., Matejka, C., & Kim, H. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.782695 · Cited by 35 · see citing works
Uddin, G. M., Youngson, N. A., Chowdhury, S. S., Hagan, C., Sinclair, D. A., & Morris, M. J. (2020) · Cells · doi:10.3390/cells9040791 · Cited by 32 · see citing works
“In our previous NMN studies adult female mice received HFD for 12 weeks [23] or 18 weeks in combination maternal HFD [18].”
BackgroundMethodResultInfluentialSelf-citationRole and Potential Mechanisms of Nicotinamide Mononucleotide in Aging
Rahman, S. U., Qadeer, A., & Wu, Z. (2024) · Aging and disease · doi:10.14336/ad.2023.0519-1 · Cited by 34 · see citing works
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NAD+ precursor supplementation in human ageing: clinical evidence and challenges
Vinten, K. T., Trętowicz, M. M., Coskun, E., van Weeghel, M., Cantó, C., Perez, R. Z., Janssens, G. E., & Houtkooper, R. H. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01387-7 · Cited by 32 · see citing works
“…studies have demonstrated that NR and NMN can effectively increase NAD + biosynthesis in the circulation as well as in tissues such as the muscle 104,105 , brain 106,107 , pancreas 5 , lung 5 , liver 5,104,105 , blood vessel (aorta) 108 and brown adipose tissue 104 following oral administration.”
Walzik, D., Jonas, W., Joisten, N., Belen, S., Wüst, R. C. I., Guillemin, G. J., & Zimmer, P. (2023) · Acta Physiologica · doi:10.1111/apha.13921 · Cited by 32 · see citing works
Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide
Zheng, C., Li, Y., Wu, X., Gao, L., & Chen, X. (2024) · Nutrients · doi:10.3390/nu16142354 · Cited by 26 · see citing works
Assiri, M. A., Ali, H., Marentette, J., Yun, Y., Liu, J., Hirschey, M. D., Saba, L. M., Harris, P. S., & Fritz, K. S. (2019) · Human Genomics · doi:10.1186/s40246-019-0251-1 · Cited by 25 · see citing works
“Several reports have demonstrated that a dose of 500 mg/kg of NMN successfully increased liver NAD levels, prevented glucose intolerance in type 2 diabetes, improved insulin sensitivity, and prevented aging-related symptoms through multiple mechanisms [20, 66, 70].”
BackgroundBenjamin, C., & Crews, R. (2024) · Metabolites · doi:10.3390/metabo14060341 · Cited by 23 · see citing works
“Beyond its established role as an NAD+ precursor, NMN demonstrates emerging regulatory functions in mitochondrial [54,118,119] and neuronal [120–122] metabolic processes.”
BackgroundEscalante‐Covarrubias, Q., Mendoza-Viveros, L., González-Suárez, M., Sitten-Olea, R., Velázquez‐Villegas, L. A., Becerril-Pérez, F., Pacheco-Bernal, I., Carreño‐Vázquez, E., Sanchez, P. B. M., Bustamante-Zepeda, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37286-2 · Cited by 24 · see citing works
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Self-citationAflatounian, A., Paris, V. R., Richani, D., Edwards, M. C., Cochran, B. J., Ledger, W. L., Gilchrist, R. B., Bertoldo, M. J., Wu, L. E., & Walters, K. A. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101583 · Cited by 23 · see citing works
“models [46,68,69], we propose that the profound differences in liver triglycerides with NMN treatment in this PCOS model are secondary to a resolution of hyperinsulinaemia, which is itself driven by peripheral insulin resistance.”
BackgroundPourabdi, R., Shahidi, F., Tabandeh, M. R., & Salehpour, M. (2024) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-024-01066-3 · Cited by 22 · see citing works
“…[ 28 ], it is expected that changes in cellular NAD + levels in response to environmen - tal stresses such as HFD and T2D [48 ], exercise [ 6 , 41 ] or circadian oscillation mediated by circadian clocks [ 27 , 30 ], maybe the primary mechanism by which the mitochondrial oxidative function is…”
Dynamic Aging: Channeled Through Microenvironment
Tan, Q., Liang, N., Zhang, X., & Li, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.702276 · Cited by 21 · see citing works
Zhang, Y., Zhu, W., Wang, M., Xi, P., Wang, H., & Tian, D. (2023) · IUBMB Life · doi:10.1002/iub.2707 · Cited by 19 · see citing works
“found that exercise and NMN partially ameliorate the pathophysiology of HFD-induced obesity in female mice.(26) However, the combination of NMN and exercise treatment hindered the benefits of exercise training for glucose regulation.”
BackgroundNAD+: An old but promising therapeutic agent for skeletal muscle ageing
Xu, Y., & Xiao, W. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102106 · Cited by 19 · see citing works
Influence of anaerobic and aerobic exercise on age-related pathways in skeletal muscle
Navas‐Enamorado, I., Bernier, M., Brea‐Calvo, G., & de Cabo, R. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.04.005 · Cited by 19 · see citing works
“Intraperitoneal administration of NMN significantly increases NAD+ levels both in liver and muscle of diet-induced obese mice, but leads to improvement in glucose tolerance and the recovery in citrate synthase activity only in the liver (Uddin et al., 2016).”
BackgroundInfluentialPhysical exercise elicits UPRmt in the skeletal muscle: The role of c-Jun N-terminal kinase
Gaspar, R. S., Katashima, C. K., Crisol, B., Carneiro, F. S., Sampaio, I. H., Silveira, L. R., da Silva, A. S. R., Cintra, D. E., Pauli, J. R., & Ropelle, E. R. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101816 · Cited by 19 · see citing works
Safety Evaluation for Restorin® NMN, a NAD+ Precursor
Turner, J. R., Licollari, A., Mihalcea, E., & Tan, A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.749727 · Cited by 18 · see citing works
“Many mouse models of disease, including obesity (Stromsdorfer et al., 2016; Uddin et al., 2016; Uddin et al., 2017), diabetes (Revollo et al.”
BackgroundThe Role of Mineral Deficiencies in Insulin Resistance and Obesity
Sagor, M. A. T., Mehjabeen, R., Shuvo, A. P. R., Raihan, S., Jahan, R., Simin, F. A., Rahman, A., Biswas, S., & Salem, L. (2021) · Current Diabetes Reviews · doi:10.2174/1573399818666211117104626 · Cited by 18 · see citing works
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Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration
You, Y., Gao, Y., Wang, H., Li, J., Zhang, X., Zhu, Z., & Liu, N. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.604404 · Cited by 16 · see citing works
“…adult fitness, For instance, it is reported that long-term administration of NMN could mitigate age-associated physiological decline in mice (Mills et al., 2016) and short-term administration of NMN could induce similar reversal of the glucose intolerance induced by obesity (Uddin et al., 2016).”
BackgroundNQO1 regulates mitotic progression and response to mitotic stress through modulating SIRT2 activity
Kang, H.-J., Song, H. Y., Ahmed, M. A. H., Guo, Y., Zhang, M., Chen, C., Cristofanilli, M., Horiuchi, D., & Vassilopoulos, A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.009 · Cited by 14 · see citing works
Hypoxic Training in Obese Mice Improves Metabolic Disorder
Wang, R., Guo, S., Tian, H., Huang, Y., Yang, Q., Zhao, K., Kuo, C., Hong, S., Chen, P., & Liu, T. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00527 · Cited by 14 · see citing works
The Role of Mitochondria in Metabolic Syndrome–Associated Cardiomyopathy
Li, J., Li, J., Chen, Y., Hu, W., Gong, X., Qiu, H., Chen, H., Xin, Y., & Li, H. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9196232 · Cited by 16 · see citing works
“NMN can improve various metabolic complications related with obesity, although this e ff ect on many other obesity-related metabolomic complications is yet to be explored [88].”
Bertoldo, M. J., Uddin, G. M., Youngson, N. A., Agapiou, D., Walters, K. A., Sinclair, D. A., Morris, M. J., & Gilchrist, R. B. (2018) · Human Reproduction Open · doi:10.1093/hropen/hoy010 · Cited by 13 · see citing works
“It is possible to achieve the same effect of 8.5 weeks of exercise with 2.5 weeks of NMN injections, as we have previously demonstrated (Uddin et al., 2016).”
BackgroundMethodResultInfluentialSelf-citationImportance of NAD+ Anabolism in Metabolic, Cardiovascular and Neurodegenerative Disorders
Helman, T. J., & Braidy, N. (2022) · Drugs & Aging · doi:10.1007/s40266-022-00989-0 · Cited by 12 · see citing works
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“…(J. Yoshino et al. 2011), insulin sensitivity in the adipocyte-specific Nampt knock-out mice (Stromsdorfer et al. 2016) and aged wild-type C57/6J mice (Mills et al. 2016), and plasma glucose concentration during glucose tolerance test in high-fat diet fed C57/6J female mice (Uddin et al. 2016).”
Miranda, E. R., Varshney, P., Mazo, C. E., Shadiow, J., Ludlow, A. T., & Haus, J. M. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103300 · Cited by 6 · see citing works
Effect of β-nicotinamide mononucleotide on tumor formation and growth in a lung cancer mouse model
Pan, F., Kang, S., Zhao, Y., Dai, L., Shao, Q., Yang, Y., Chen, Q., Zhu, J., & Cui, L. (2020) · Materials Chemistry Frontiers · doi:10.1039/d0qm00897d · Cited by 5 · see citing works
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NAD+ homeostasis and its role in exercise adaptation: A comprehensive review
Jiang, Z., Luo, X., Han, C., Qin, Y.-Y., Pan, S.-Y., Qin, Z.-H., Bao, J., & Luo, L. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.09.036 · Cited by 5 · see citing works
Protein Acetylation and NAD+ Homeostasis in Aging Muscle
Ji, L. L. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-88361-3_17 · Cited by 3 · see citing works
Chen, T., Tang, Q., Yu, B., Tang, L. Y., Lin, J., Zhang, L., Shan, W., & Yu, H. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120505 · Cited by 3 · see citing works
NAD+: a crucial regulator of sirtuin activity in aging
Braidy, N., & Villalva, M. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-814118-2.00008-2 · Cited by 3 · see citing works
Yu, J., Youngson, N. A., Laybutt, D. R., Morris, M. J., & Leigh, S. (2023) · Physiological Genomics · doi:10.1152/physiolgenomics.00066.2023 · Cited by 3 · see citing works
Self-citationBertoldo, M. J., Andraweera, P. H., Bromfield, E. G., Cousins, F. L., Lindsay, L. A., Paiva, P., Regan, S. L. P., Rose, R., & Akison, L. K. (2018) · Reproduction Fertility and Development · doi:10.1071/rd17445 · Cited by 3 · see citing works
Yao, S., Prates, K. V., Freydenzon, A., Assante, G., McRae, A. F., Morris, M. J., & Youngson, N. A. (2024) · The FASEB Journal · doi:10.1096/fj.202301546rr · Cited by 2 · see citing works
Self-citationEscalante‐Covarrubias, Q., Mendoza-Viveros, L., González-Suárez, M., Becerril-Pérez, F., Pacheco-Bernal, I., Carreño‐Vázquez, E., Sanchez, P. B. M., Bustamante-Zepeda, M., Orozco-Solís, R., & Aguilar‐Arnal, L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.12.503453 · Cited by 2 · see citing works
Neuronal C/EBPβ Shortens the Lifespan via Inactivating NAMPT
Li, B., Xie, Z., Wang, M., Nie, S., Qian, Z., Meng, X., Liu, X., Kang, S. S., & Ye, K. (2025) · Advanced Science · doi:10.1002/advs.202414871 · Cited by 1 · see citing works
Tao, H., Dong, Q., Long, Y. L., Liu, L., Qin, S., & Wang, Y. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.178562 · Cited by 1 · see citing works
Screening of Natural High-producing NMN strains and Microbial Synthesis of NMN by Nampt
Li, C., Long, Z., Zhang, H., Lin, Y., & Zhao, L. (2023) · Food Nutrition Chemistry · doi:10.18686/fnc.v1i1.7 · Cited by 1 · see citing works
烟酰胺腺嘌呤二核苷酸（NAD+）合成代谢及其调控机体衰老研究进展
Li, Y., Tian, X., Luo, J., Bao, T., & Wu, X. (2024) · Scientia Sinica Vitae · doi:10.1360/ssv-2024-0004
Epigenetic Modifications Involved in Ageing Process: The Role of Histone Methylation of SET-Domain
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李超, 邹国珑, 张海潮, 林玉惠, & 赵丽青 (2023) · Food Nutrition Chemistry · doi:10.18686/zhfnc.v1i1.25 · Cited by 1 · see citing works
Vitamin B3 salvage and NAD\(^+\) metabolism in skeletal muscle
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Endothelial C/EBPβ/AEP pathway drives vascular deterioration and systemic aging
Li, B., Nie, S., Wang, M., An, J., Qian, Z., Meng, X., Edgington‐Mitchell, L. E., Zhang, Z., Yang, X., & Ye, K. (2026) · Science Advances · doi:10.1126/sciadv.aed1961
- Authors
- Uddin, G. M., Youngson, N. A., Sinclair, D. A., & Morris, M. J.
- Affiliations
- UNSW Sydney (AU)
- Harvard University (US)
- Corresponding author
- Morris, Margaret J.
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2016-08-19
- Volume
- 7
- Pages
- 258-258
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC4990541
- OpenAlex
- W2509657334
- Cited by
- 95
- References
- 54
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 15 · 2022: 11 · 2021: 10 · 2020: 13 · 2019: 11 · 2018: 9 · 2017: 9
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council (1044295)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- nicotinamide mononucleotide, NAD+ precursors, physical activity, obesity, high-fat diet, glucose tolerance, insulin, mitochondrial function, citrate synthase, NAD levels, muscle, liver, adiposity, female mice
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