Abstract: Objective · To study the effects of Roux-en-Y gastric bypass (RYGB) surgery on hepatic glycolipid metabolism in the rat models with obesity combined with type 2 diabetes mellitus (T2DM) and investigate the molecular mechanisms involved.  Methods · The rats were randomly divided into control group, high-fat diet+DM group, sham-operated group and operated group, ten each. The changes of body weights and food intakes, as well as the results of intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were monitored. The mRNA and protein expressions of farnesoid X receptor (FXR), fibroblast growth factor 21 (FGF21) and glucose-6-phosphatase (G6Pase) were respectively detected.  Results · The body weights and food intakes were significantly reduced in operated group, as compared to the high-fat diet+DM group and sham-operated group.The areas under the curve of IPGTT and ITT in operated group were reduced. Meanwhile, red lipid droplets of the operated group were obviously less than those of high-fat diet+DM group and sham-operated group by oil red-O staining. Furthermore, the mRNA expressions of FXR and FGF21 in operated group were significantly higher than those of high-fat diet+DM group and sham-operated group, while G6Pase mRNA expression was reduced. The protein levels of FXR and FGF21 were also higher in operated group than in high-fat diet+DM group and sham-operated group, but G6Pase level was decreased.  Conclusion · RYGB could improve the glycolipid metabolism of rats with obesity combined with T2DM by activating FXR-G6Pase pathway.

Key words:  bile acid, farnesoid X receptor, Roux-en-Y gastric bypass, obesity, type 2 diabetes mellitus, glucolipid metabolism