Molecular Insights of Improved Cholesterol Metabolism Following Vertical Sleeve Gastrectomy in Diet Induced Obese Rats
6/10/2012 12:00:00 PM
6/10/2012 2:00:00 PM
, ERIC P. SMITH, RON BITNER, DREW KAISER, HELENA GYLLING, HILARY E. WILSON-PEREZ, RANDY J.. SEELEY, DAVID A.. D'ALESSIO,
Vertical sleeve gastrectomy (VSG), a new bariatric surgical procedure in which the majority of the stomach is removed while leaving the intestine intact, is gaining in popularity. This study was designed to determine the effect of VSG on lipid metabolism, and to exam the molecular mechanisms involved. Blood samples and tissue biopsies were obtained at 6 months after the VSG or sham surgery (n=7 per group) following fasting-refeeding. Total fat absorption and oral fat tolerance were measured 1 week before sacrifice. Plasma markers of cholesterol absorption (campesterol, sitosterol, avenasterol, and cholestanol) and synthesis (cholestenol, desmosterol, squalene, and lathosterol) were measured by gas-liquid chromatography. mRNA expression levels of genes related to cholesterol absorption, including AbcA1, apoA-IV, apoE, and SCARB1, cholesterol synthesis, including HMG-CoA reductase, HMG-CoA synthase, mevalonate kinase and squalene synthase, and genes pertaining to bile metabolism, including AbcG5, AbcG8, Cyp7a1 and Cyp7b1 were determined. VSG improved fat tolerance, while fat absorption and cholesterol absorption was unchanged at 6 months following VSG. Plasma markers of cholesterol synthesis were reduced by VSG by 14-34% vs. sham, and mRNA expression of genes related to cholesterol synthesis was significantly reduced. The increased expression of hepatic AbcG5, AbcG8 indicated activated biliary secretion of liver cholesterol, and the increased expression of Cyp7a1, Cyp7b1 indicated stimulated hepatic bile synthesis. Our data suggest that the improved cholesterol metabolism after VSG is related to reduced intestinal cholesterol synthesis, enhanced hepatic bile production and increased hepato-biliary cholesterol transport, thus providing a novel mechanistic explanation for the improved cholesterol metabolism following VSG.
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