Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD-induced obese mice

Abstract

The present study aimed to investigate the effect of metformin on the induction of autophagy in the liver and adipose tissues of a mouse model of obesity. C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity-associated hepatic steatosis, and treated with metformin (150 mg/kg/d) by intraperitoneal injection for the final 4 weeks of HFD feeding. Body weight was recorded weekly, and the food intake of the mice was recorded daily during the treatment period. Liver and adipose tissues were harvested for histological and molecular analyses. The results revealed that metformin significantly reduced body weight without altering food intake in the HFD mice, particularly in the epididymal white adipose tissue (eWAT). Metformin treatment ameliorated HFD-induced hepatic steatosis and serum levels of triglycerides, which was consistent with a marked increase in the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and AMP-activated protein kinase (AMPK) in the liver following metformin treatment. However, metformin suppressed the expression of LC3 in the eWAT without altering the expression of AMPK, compared with that in the HFD mice. In conclusion, metformin reduced the body weight and hepatic steatosis of the HFD-induced obese mice, without altering food intake. The effects of metformin treatment may be attributable to the improved induction of hepatic autophagy and the inhibited induction of adipose tissue autophagy.

Effects of Metformin Combined with Lactoferrin on Lipid Accumulation and Metabolism in Mice Fed with High-Fat Diet

“…In Li’s study and Woo’s study, the mice were fed with HFD for 12 weeks and Met were treated from the last four weeks. The former study showed a decrease in body weight, epididymal white adipose, and serum TG level with no effect on liver weight [ 7 ]; however, the latter study found a decrease in liver weight, with no effects on body weight and adiposity [ 8 ]. For Lf, both Sun and Xiong found that long-term administration decreased body weight, fat weight, and serum and hepatic TG in the obese mice maintained on a HFD [ 18 , 19 ].…”

“…Met exhibits beneficial effect on weight loss of obese individuals [ 3 ] and western diet-induced mouse models [ 4 ]. Met treatment also decreased adipose tissue weight, improved lipid profiles, and lightened the severity of high fat induced hepatic steatosis in human subjects and obese mice [ 5 , 6 , 7 , 8 ]. However, Met has transient mild gastrointestinal adverse effects, such as nausea, vomiting, and diarrhea, especially during the initiation of therapy [ 9 ].…”

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

“…This geroprotective potential paired with its little side effects has propelled the start of several clinical trials. Metformin recapitulates important metabolic effects of CR (Onken and Driscoll, 2010) and stimulates protective autophagy, for instance in mouse models of obesity and cardiac dysfunction (Li et al, 2017a;Xie et al, 2011).…”

Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

“…These symptoms may not only cause diabetes, but can also promote chronic liver fibrosis and liver cancer [2]. A recent study pointed out that new therapy targets of hepatic steatosis mainly block lipid generation and accumulation in the liver, leading to the decomposition of fat oil droplets, enhancing the β-oxidation metabolism of fatty acids, and maintaining mitochondrial function [14,38,39].…”