Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice

Karise, Iara; Bargut, Thereza Cristina Lonzetti; Sol, Mariano del; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1016/j.biopha.2019.01.021

Cited by 61 publications

(41 citation statements)

References 54 publications

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“…This is, to our knowledge, the first study to show signs of an upregulatory effect of oral BC supplementation on BAT activation in mice, even though effects in this sense are well-known for vitamin A treatment in the form of retinoic acid [ 13 , 14 ]. As for MET treatment, the early literature showed a lack of effect on BAT activity in obese rats [ 45 ] and normal mice [ 46 ], yet more recent studies indicate that MET is uptaken by BAT in vivo in mice [ 47 ] and can enhance BAT mitochondrial content and thermogenic capacity [ 48 , 49 , 50 ]. Our results indicate that the effects of single BC and MET treatments favoring activation of BAT in mice on an HFD are not additive.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

et al. 2021

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Anti-obesity activity has been reported for beta-carotene (BC) supplementation at high doses and metformin (MET). We studied whether BC treatment at a closer to dietary dose and MET treatment at a lower than therapeutic dose are effective in ameliorating unwanted effects of an obesogenic diet and whether their combination is advantageous. Obesity-prone mice were challenged with a high-fat diet (HFD, 45% energy as fat) for 4 weeks while receiving a placebo or being treated orally with BC (3 mg/kg/day), MET (100 mg/kg/day), or their combination (BC+MET); a fifth group received a placebo and was kept on a normal-fat diet (10% energy as fat). HFD-induced increases in body weight gain and inguinal white adipose tissue (WAT) adipocyte size were attenuated maximally or selectively in the BC+MET group, in which a redistribution towards smaller adipocytes was noted. Cumulative energy intake was unaffected, yet results suggested increased systemic energy expenditure and brown adipose tissue activation in the treated groups. Unwanted effects of HFD on glucose control and insulin sensitivity were attenuated in the treated groups, especially BC and BC+MET, in which hepatic lipid content was also decreased. Transcriptional analyses suggested effects on skeletal muscle and WAT metabolism could contribute to better responses to the HFD, especially in the MET and BC+MET groups. The results support the benefits of the BC+MET cotreatment.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

et al. 2021

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“…By PET/CT imaging, it was found that metformin was mainly taken up by BAT in vivo through the increased expression of OCT (organic cation transporter) (10). It was shown that metformin exerts its anti-obesity effects through increasing mitochondrial biogenesis, decreasing fatty acid uptake, and stimulating thermogenesis (89). Moreover, a study indicated that in rats, metformin modulates gut microbiota and prevents high-fat diet induced obesity, which increased the abundance of short-chain fatty acid producing bacteria and decreased microbial diversity (90).…”

Section: Metformin and Obesitymentioning

confidence: 99%

Metformin and Its Benefits for Various Diseases

2020

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Metformin is a widely used biguanide drug due to its safety and low cost. It has been used for over 60 years to treat type 2 diabetes at the early stages because of its outstanding ability to decrease plasma glucose levels. Over time, different uses of metformin were discovered, and the benefits of metformin for various diseases and even aging were verified. These diseases include cancers (e.g., breast cancer, endometrial cancer, bone cancer, colorectal cancer, and melanoma), obesity, liver diseases, cardiovascular disease, and renal diseases. Metformin exerts different effects through different signaling pathways. However, the underlying mechanisms of these different benefits remain to be elucidated. The aim of this review is to provide a brief summary of the benefits of metformin and to discuss the possible underlying mechanisms.

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“…WAT to beige or BAT transdifferentiation has been recognized as a potential therapeutic target for obesity and related metabolic disease prevention and management [49]. Metformin might increase BAT thermogenic markers and mitochondrial biogenesis, promoting brown adipocyte proliferation and differentiation [50]. Inhibition of autophagy leads to increased levels of uncoupling protein 1 (UCP1), which regulates the browning of WAT and beige adipocytes [26,51].…”

Section: Discussionmentioning

confidence: 99%

Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation

Cruciani

Garroni

Pala

et al. 2021

IJMS

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Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.

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Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice

Cited by 61 publications

References 54 publications

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

Metformin and Its Benefits for Various Diseases

Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation

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