Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid X receptor pathway.

Abstract

BACKGROUNDBile acids play an important role in the amelioration of type 2 diabetes following duodenal-jejunal bypass (DJB). Serum bile acids are elevated postoperatively. However, the clinical relevance is not known. Bile acids in the peripheral circulation reflect the amount of bile acids in the gut. Therefore, a further investigation of luminal bile acids following DJB is of great significance.AIMTo investigate changes of luminal bile acids following DJB.METHODSSalicylhydroxamic acid (SHAM), DJB, and DJB with oral chenodeoxycholic acid (CDCA) supplementation were performed in a high-fat-diet/streptozotocin-induced diabetic rat model. Body weight, energy intake, oral glucose tolerance test, luminal bile acids, serum ceramides and intestinal ceramide synthesis were analyzed at week 12 postoperatively.RESULTSCompared to SHAM, DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of farnesoid X receptor (FXR) - inhibitory bile acids within the common limb. Intestinal ceramide synthesis was repressed with decreased serum ceramides, and this phenomenon could be partially antagonized by luminal supplementation of FXR activating bile acid CDCA.CONCLUSIONDJB significantly changes luminal bile acid composition with increased proportion FXR-inhibitory bile acids and reduces serum ceramide levels. There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.