Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats
Open accessAbstract
OBJECTIVE: Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats. METHODS: In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water) or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old. RESULTS: Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE) did not change, baseline respiratory quotient (RQ) was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle. CONCLUSION: From the results obtained, beneficial effects of metformin on visceral fat reduction has been demonstrated probably through a mechanism for a potential shift of fuel resource into fat oxidation and an upregulation of adaptive thermogenesis independent of an anorexigenic effect of this drug.
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Metformin up-regulates fat oxidation-related enzyme in liver, UCP-1 in brown adipose tissue, and UCP-3 in skeletal muscle, supporting a possible mechanism of enhanced fat oxidation.
“Moreover, an up-regulation of fat oxidation-related enzyme in the liver, of UCP-1 in the brown adipose tissue, and of UCP-3 in the skeletal muscle were found to support a possible mechanism of enhancement of fat oxidation [156].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [156]
Metformin significantly reduces visceral fat independently of diabetes in rats and in diabetic and non-diabetic people.
“A study investigating weight loss and energy metabolism by this drug in rats and in diabetic and non-diabetic people, found a significant reduction of visceral fat independently of diabetes.”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [156]
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Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
Kahn, S. E., Haffner, S. M., Heise, M. A., Herman, W. H., Holman, R. R., Jones, N. P., Kravitz, B. G., Lachin, J. M., O'Neill, M. C., Zinman, B., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa066224 · Cited by 2,962 · see citing works
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
Developmental Origin of Fat: Tracking Obesity to Its Source
Gesta, S., Tseng, Y.-H., & Kahn, C. R. (2007) · Cell · doi:10.1016/j.cell.2007.10.004 · Cited by 1,508 · see citing works
The AMP‐Activated Protein Kinase: Fuel Gauge of the Mammalian Cell?
Hardie, D. G., & Carling, D. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00259.x · Cited by 1,317 · see citing works
Metabolic effects of metformin in non-insulin-dependent diabetes mellitus
Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., & Gerich, J. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508313330903 · Cited by 1,148 · see citing works
Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP
Miller, R., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M. J. (2013) · Nature · doi:10.1038/nature11808 · Cited by 828 · see citing works
Musi, N., Hirshman, M. F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., Zhou, G., Williamson, J. M., Ljunqvist, O., Efendic, S., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2074 · Cited by 806 · see citing works
Dealing with energy demand: the AMP-activated protein kinase
Kemp, B. E., Mitchelhill, K. I., Stapleton, D., Michell, B. J., Chen, Z., & Witters, L. A. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01340-1 · Cited by 521 · see citing works
Lusk, G. (1924) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)85293-0 · Cited by 371 · see citing works
Lusk, G. (1924) · Journal of Biological Chemistry · Cited by 355 · see citing works
Regulation of Hepatic Acetyl Coenzyme A Carboxylase by Phosphorylation and Dephosphorylation
Carlson, C. A., & Kim, K.-H. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44486-4 · Cited by 346 · see citing works
Drugs Commonly Associated With Weight Change: A Systematic Review and Meta-analysis
Domecq, J. P., Prutsky, G. J., Leppin, A. L., Sonbol, M. B., Altayar, O., Undavalli, C., Wang, Z., Elraiyah, T. A., Brito, J. P., Mauck, K. F., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3421 · Cited by 334 · see citing works
AMP‐activated protein kinase: role in metabolism and therapeutic implications
Schimmack, G., DeFronzo, R. A., & Musi, N. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00561.x · Cited by 229 · see citing works
Uncoupling proteins: their roles in adaptive thermogenesis and substrate metabolism reconsidered
Dulloo, A. G., & Samec, S. (2001) · British Journal Of Nutrition · doi:10.1079/bjn2001412 · Cited by 166 · see citing works
Ke, J., Kliewer, K., Hamad, E. M., Cole, R. M., Powell, K. A., Andridge, R., Straka, S. R., Yee, L. D., & Belury, M. A. (2015) · Nutrition & Metabolism · doi:10.1186/1743-7075-12-1 · Cited by 142 · see citing works
Huang, K., Liang, X., Zhong, Y., He, W., & Wang, Z. (2014) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.6896 · Cited by 121 · see citing works
Velasco, G., Geelen, M. J. H., & Guzmán, M. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.9784 · Cited by 115 · see citing works
Diabetes in the Western Pacific Region—Past, Present and Future
Chan, J. C. N., Cho, N. H., Tajima, N., & Shaw, J. E. (2013) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2013.11.012 · Cited by 97 · see citing works
Metformin and Parameters of Physical Health
Helvacı, M. R., Kaya, H., Borazan, A., Özer, C., Seyhanli, M., & Yalçın, A. (2008) · Internal Medicine · doi:10.2169/internalmedicine.47.0787 · Cited by 87 · see citing works
Matthaei, S., Reibold, J. P., Hamann, A., Benecke, H., Häring, H.-U., Greten, H., & Klein, H. H. (1993) · Endocrinology · doi:10.1210/endo.133.1.8391425 · Cited by 83 · see citing works
Metformin and Berberine Prevent Olanzapine-Induced Weight Gain in Rats
Hu, Y., Young, A. J., Ehli, E. A., Nowotny, D., Davies, P. S., Droke, E. A., Soundy, T. J., & Davies, G. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093310 · Cited by 76 · see citing works
Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity
Zemel, M. B., & Bruckbauer (2013) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s40840 · Cited by 74 · see citing works
Fruehwald‐Schultes, B., Oltmanns, K. M., Toschek, B., Sopke, S., Kern, W., Jan Born, A., Fehm, H. L., & Peters, A. (2002) · Metabolism · doi:10.1053/meta.2002.31332 · Cited by 68 · see citing works
Metformin in Noninsulin‐Dependent Diabetes Mellitus
Lee, A. J. (1996) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.1996.tb02964.x · Cited by 61 · see citing works
Insulin-independent diabetes: A defect in the activity of lipoprotein lipase in adipose tissue
Taylor, K. G., Galton, D. J., & Holdsworth, G. (1979) · Diabetologia · doi:10.1007/bf01223620 · Cited by 59 · see citing works
News Feature: Asia's big problem
Mandavilli, A., & Cyranoski, D. (2004) · Nature Medicine · doi:10.1038/nm0404-325 · Cited by 52 · see citing works
Féry, F., Plat, L., & BALASSE, E. O. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90307-3 · Cited by 52 · see citing works
Body composition in adults with newly diagnosed type 2 diabetes: effects of metformin
Aghili, R., Malek, M., Valojerdi, A. E., Banazadeh, Z., Najafi, L., & Khamseh, M. E. (2014) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/s40200-014-0088-z · Cited by 45 · see citing works
Intracerebroventricular Injection of Metformin Induces Anorexia in Rats
Lee, C. K., Choi, Y. J., Park, S., Kim, J. Y., Won, K. C., & Kim, Y. W. (2012) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2012.36.4.293 · Cited by 33 · see citing works
Kim, H. J., Park, E.-Y., Oh, M.-J., Park, S. S., Shin, K.-H., Choi, S.-H., Chun, B., & Kim, D. H. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00099.2013 · Cited by 22 · see citing works
Tessari, P., & Tiengo, A. (2008) · Acta Diabetologica · doi:10.1007/s00592-008-0032-0 · Cited by 21 · see citing works
Wada, N., Hashinaga, T., Otabe, S., Yuan, X., Kurita, Y., Kakino, S., Ohoki, T., Nakayama, H., Fukutani, T., Tajiri, Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067712 · Cited by 21 · see citing works
Self-citationDoes long-term metformin treatment increase cardiac lipoprotein lipase?
Hauton, D. (2010) · Metabolism · doi:10.1016/j.metabol.2009.12.015 · Cited by 20 · see citing works
Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons
Rouquet, T., Clément, P., Gaigé, S., Tardivel, C., Roux, J., Dallaporta, M., Bariohay, B., Troadec, J., & Lebrun, B. (2014) · Obesity · doi:10.1002/oby.20902 · Cited by 17 · see citing works
Avignon, A., Lapinski, H., RABASA-LHORET, R. P. R., Caubel, C., Boniface, H., & Monnier, L. (2000) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2000.00082.x · Cited by 10 · see citing works
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Lactate modulation of immune responses in inflammatory versus tumour microenvironments
Certo, M., Tsai, C.-H., Pucino, V., Ho, P.-C., & Mauro, C. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-0406-2 · Cited by 924 · see citing works
Metformin: Mechanisms in Human Obesity and Weight Loss
Yerevanian, A., & Soukas, A. A. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00335-3 · Cited by 414 · see citing works
Salvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Di Martino, A., Albanese, G., Colantuoni, S., Medicamento, G., et al. (2022) · Biomolecules · doi:10.3390/biom12020176 · Cited by 62 · see citing works
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- Authors
- Tokubuchi, I., Tajiri, Y., Iwata, S., Hara, K., Wada, N., Hashinaga, T., Nakayama, H., Mifune, H., & Yamada, K.
- Affiliations
- Kurume University (JP)
- Corresponding author
- Tajiri, Yuji
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-02-03
- Volume
- 12
- Issue
- 2
- Pages
- e0171293
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5291441
- OpenAlex
- W2584709305
- Cited by
- 121
- References
- 38
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 15 · 2023: 13 · 2022: 23 · 2021: 17 · 2020: 13 · 2019: 12 · 2018: 12 · 2017: 4
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- metformin, energy metabolism, visceral fat, fatty acid oxidation, adaptive thermogenesis, respiratory quotient, plasma lactate, pyruvate, type 2 diabetes, brown adipose tissue, skeletal muscle, UCP1, UCP3, body composition
- MeSH terms
- Adult, Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Fatty Acids, Female, Humans, Male, Metformin, Middle Aged, Oxidation-Reduction, Biomarkers, Case-Control Studies, Postprandial Period, Intra-Abdominal Fat, Lipid Metabolism, Rats
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