Roux-en-Y gastric bypass reduces lipid overaccumulation in liver by upregulating hepatic autophagy in obese diabetic rats.

BACKGROUND

The decrease in lipotoxicity is one of the crucial mechanisms by which Roux-en-Y gastric bypass (RYGB) improves insulin sensitivity. Little work, however, has been performed to elucidate the exact mechanism of RYGB reducing hepatic lipid overaccumulation in response to heavy lipid and glucose challenge. Here, we explored the effects of RYGB on hepatic autophagy in obese diabetic rats.

METHODS

Sprague-Dawley rats were divided into five groups: diabetic RYGB, diabetic RYGB sham, diabetic food restriction (FR), diabetic rats, and non-diabetic controls (n = 12/group). At 4-week post-operation, genetic and protein expressions of autophagy markers including Atg7 and Beclin 1 and the conversion of LC3 were examined with quantitative RT-PCR and Western blotting. Plasma glucagon-like peptide-1 (GLP-1) and triglyceride and total cholesterol levels in liver tissue were tested.

RESULTS

In both genetic and protein levels, we observed a significant upregulated autophagy in liver at 4 weeks after RYGB. Restored autophagy in liver played a key role in reducing the hepatic lipid burden in obese diabetic rats. The marked increase of autophagy in liver after RYGB correlated well with the plasma GLP-1 level.

CONCLUSIONS

Our data demonstrate that RYGB significantly upregulated hepatic autophagy. We suggest that the effects of RYGB on autophagy in liver may be due to the increased GLP-1 level after surgery. Moreover, the activated autophagy in liver might play a key role in reducing the hepatic lipid overaccumulation after RYGB.