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 transsulfuration and purine metabolism via flux changes in 1-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 1-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease. 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 1-carbon cycle in the liver were analyzed by real-time polymerase chain reaction 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-fed rats and mice. Metabolic analyses revealed that the possible underlying mechanism may involve decreased S-adenosylmethionine (SAM)-to-S-adenosylhomocysteine ratio via downregulation of SAM synthesizing enzyme and upregulation 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 decreasing those of PEMT and BHMT, a change in 1-carbon metabolism that may decrease the ratio of SAM to S-adenosylhomocysteine, thereby resulting in the prevention of fat accumulation in the liver. Thus, we suggest that the change in 1-carbon metabolism, especially the SAM metabolism, may contribute to the improvement of diet-induced fatty liver disease after DJB surgery.

Keywords: 1-Carbon metabolism; Metabolic surgery; NAFLD; Obesity; S-adenosylhomocysteine; S-adenosylmethionine.