The Role of Pancreatic Fatty Acid Synthesis in Islet Morphology and Function after Caloric Restriction or Roux-En-Y Gastric Bypass Surgery in Mice

Background: Both caloric restriction (CR) and Roux-en-Y gastric bypass (RYGB) are practical interventions for type 2 diabetes mellitus (T2DM), while the molecular mechanisms of CR and RYGB regarding glycemic control are still poorly understood. Here, we explore the effects and underlying mechanisms of CR and RYGB on beta-cell area and function. Methods: Average islet size was measured by histological analysis. The pancreatic lipid content was detected by using a commercial lipid assay kit. The expression levels of lipogenic transcription factors and enzymes in mouse pancreas were determined by quantitative PCR, Western blot, and immunofluorescence. Results: CR decreased the mean size of islets and pancreatic insulin production in both regular diet-fed and high-fat diet-fed mice. Increased beta-cell apoptosis was detected in the calorie-restricted mice. Interestingly, the lipogenic transcription factors and enzymes such as SREBP1c, PPAR gamma, FASN and ACC were upregulated in the pancreas after CR. In contrast to CR, RYGB decreased the apoptosis of beta-cells and the expression of fatty acid synthase. Conclusions: Pancreatic fatty acid synthesis is critical to the beta-cell function after CR and RYGB.