J Nutr Health.  2013 Aug;46(4):307-314.

Effects of resveratrol on hepatic autophagy in high fat diet-induced obese mice

• Lee HJ
• Yang SJ

Abstract

Resveratrol (RSV) exerts several beneficial effects on metabolism and metaflammation-related diseases, including diabetes and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate whether RSV affects pathophysiology of diabetes and NAFLD as well as hepatic autophagy in a rodent model of diet induced obesity (DIO). DIO was induced in a subset of C57BL/6J mice fed a high fat (HF, 45% kcal fat) diet. After six weeks of HF diet treatment, RSV (8 mg/kg/day) was administered via an osmotic pump for a period of four weeks. Therefore, the experimental groups were as follows: 1) lean control (CON), 2) HF diet-induced obese control (HF), and 3) HF_RSV. Body weight and food intake were monitored daily. Fasting glucose, insulin, and adiponectin in serum and lipid profiles in serum and liver were analyzed. In addition, the autophagic process was investigated using transmission electron microscopy (TEM). Body weight and food intake were not affected by RSV treatment. Impaired glucose control accompanied by DIO was recovered with RSV as shown by lower levels of fasting serum glucose and insulin when compared with HF obese controls. In addition, RSV treatment resulted in increased levels of serum adiponectin, however, indices of lipid profile in serum and livers were reduced. Results of TEM analysis showed that a HF diet induced excessive autophagy with the presence of double-membrane autophagosomes, which was ameliorated by RSV. The regulatory effect of RSV on autophagy was confirmed by the altered LC3-II formation, which increased with a HF diet and was decreased by RSV treatment. These results suggest that RSV treatment improves glucose control and lipid profile and these beneficial effects may be mediated by an altered autophagic process.

Keyword

autophagy; obesity; resveratrol; sirtuin

MeSH Terms

Adiponectin
Animals
Autophagy
Body Weight
Diet
Eating
Fasting
Fatty Liver
Glucose
Insulin
Liver
Mice
Mice, Obese
Microscopy, Electron, Transmission
Obesity
Rodentia
Stilbenes
Adiponectin
Fatty Liver
Glucose
Insulin
Stilbenes

Figure

• 

  Fig. 1 The effect of resveratrol (RSV) on double-membrane autophagosome formation and cell organelle morphology. RSV reduces the formation of double-membrane autophagosomes (gray arrows), and increase mitochondrial size and cristae content in livers. Original magnification: 10,000 × (A-C) and 25,000 × (D-F). CON: control, HF: high fat.

• 

  Fig. 2 The effect of resveratrol (RSV) on (A) number of autophagosomes and (B) mitochondrial DNA contents. Number of autophagosomes were analyzed from three separate images per each mouse liver. Mean ± SEM (n = 6 per group). Different letters within a variable are significantly different at p < 0.05. CON: control, HF: high fat.

• 

  Fig. 3 Representative Western blot image of LC3. LC3-II formation was analyzed in livers of control (CON), high fat diet (HF), and HF with resveratrol (HF_RSV) treated-mice. Beta-actin as a loading control.

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