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

Hee Jae Lee; Soo Jin Yang

doi:10.4163/jnh.2013.46.4.307

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Lee and Yang: Effects of resveratrol on hepatic autophagy in high fat diet-induced obese mice

Research Article

Journal of Nutrition and Health 2013; 46(4): 307-314.

Published online: 31 August 2013

DOI: https://doi.org/10.4163/jnh.2013.46.4.307

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

Hee Jae Lee, Soo Jin Yang

Department of Food and Nutrition and Human Ecology Research Institute, Chonnam National University, Gwangju 500-757, Korea.

To whom correspondence should be addressed. (sjyang89@chonnam.ac.kr)

Received 9 July 2013 Revised 31 July 2013 Accepted 19 August 2013

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: autophagy, obesity, resveratrol, sirtuin

Figures and Tables

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.

Table 1

Primers sequences

Actb: beta-actin. mtDNA: mitochondrial DNA. Actb and mtDNA were analyzed via SYBR Green chemistry

Table 2

The effect of resveratrol (RSV) on body weight change, liver weight, and food intake

Mean ± SEM (n = 6 per group). Different letters within a variable are significantly different at p < 0.05. CON: control, HF: high fat

Table 3

Serum metabolic parameters in lean control (CON) mice and high-fat (HF) fed mice treated with or without resveratrol (RSV)

Mean ± SEM (n = 6 per group). Different letters within a variable are significantly different at p < 0.05. AST: aspartate aminotransferase, ALT: alanine aminotransferase

Table 4

The effect of resveratrol (RSV) on lipid levels in serum and liver

Mean ± SEM (n = 6 per group). Different letters within a variable are significantly different at p < 0.05. CON: control, HF: high fat, TC: total cholesterol, TG: triglyceride

Notes

This research was supported by grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1004861) and Chonnam National University (2012) in Korea.

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