Sleeve Gastrectomy Suppresses Hepatic De Novo Cholesterogenesis and Improves Hepatic Cholesterol Accumulation in Obese Rats with Type 2 Diabetes Mellitus

Abstract Objectives Cholesterol metabolic disturbance increases the risk of various acquired diseases and impacts public health. An apparent correlation between hypercholesterolemia and type 2 diabetes mellitus (T2DM) was confirmed recently. Bariatric surgery can induce durable and sufficient body weight loss and T2DM remission. A previous study illustrated a cholesterol-lowering effect of sleeve gastrectomy (SG), but the intrinsic mechanism is still elusive. The present study aimed to investigate the effects of SG on hypercholesterolemia and hepatic cholesterol accumulation in a T2DM rat model. Methods Obese rats with T2DM were randomly subjected to sham operation, sham operation combined with food restriction, or SG. Body weight, food intake, blood glucose, body composition, and cholesterol level were measured at the indicated time points. Subsequently, hepatic cholesterol content and both protein and transcriptional levels of sterol regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl–coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) were measured at 2 and 4 weeks postoperatively. Results SG rapidly reduced blood glucose independent of body weight loss and food restriction. Rats that underwent SG exhibited lower total cholesterol (TC) and free cholesterol (FC) in both serum and liver. The cholesterol-lowering effect was independent of body weight loss and food restriction at just 2 weeks postoperatively. Protein and mRNA expression of SREBP2, HMGCR, and LDLR were inhibited at 2 weeks postoperatively and had recovered by 4 weeks after SG. Conclusions We illustrated that SG alleviated hypercholesterolemia and hepatic cholesterol accumulation partially by inhibiting hepatic de novo cholesterogenesis.