Duodenal-jejunal bypass maintains hepatic S-adenosylmethionine/S-homocysteine ratio in diet-induced obese rats

Abstract

We previously reported that the duodenal-jejunal bypass (DJB) surgery altered trans-sulfuration and purine metabolism via flux changes in one-carbon metabolism in the liver. In this study, we extended our study to gain further insight into mechanistic details of how the DJB-induced flux changes in one-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease (NAFLD). Rodents were subjected to surgical (sham operation and DJB) or dietary (reduced food supply to follow the weight changes in the DJB-group) interventions. The microscopic features of the liver were examined by immunohistochemistry. The expressions of genes in lipid synthesis and in one-carbon cycle in the liver were analyzed by real-time PCR and western blotting. Metabolic changes in the liver were determined. We observed that DJB reduces hepatic steatosis and improves insulin sensitivity in both high-fat diet (HFD)-fed rats and mice. Metabolic analyses revealed that the possible underlying mechanism may involve decreased SAM/SAH ratio via down-regulation of SAM synthesizing enzyme and up-regulation of SAM catabolizing enzyme. We also found in mice that DJB-mediated attenuation of hepatic steatosis is independent of weight loss. DJB also increased hepatic expression levels of GNMT while decreased those of PEMT and BHMT, a change in one-carbon metabolism that may decrease the ratio of SAM to SAH, thereby resulting in the prevention of fat accumulation in the liver. Thus, we suggest that the change in one-carbon metabolism, especially the SAM metabolism, may contribute to the improvement of diet-induced fatty liver disease after DJB surgery.