Altered Cholesterol Metabolism in a Murine Model of Vertical Sleeve Gastrectomy

Metabolic bariatric surgery is among the most effective and durable treatments for obesity. Vertical sleeve gastrectomy (VSG) has become the preferred surgical method to achieve sustained weight loss and reverse obesity-related disease, including dyslipidemias. Human studies have shown that ∼40% of VSG patients can discontinue statin treatment by 6 months. Interestingly, alterations in plasma bile acids and synthesis have been observed after bariatric surgery. Although it is well known that cholesterol is the precursor for all bile acids, the link between changes in plasma cholesterol and bile acids remains unclear in the context of VSG. Here, we present a murine model of VSG that leads to a marked decrease in plasma cholesterol levels despite no difference in body weight compared to sham surgery. Our results demonstrate that gastric resection lowers systemic cholesterol burden by promoting the hepatobiliary elimination of cholesterol through the upregulation of bile acid synthesis. These observations imply that gastric resection impacts overall hepatic physiology and cholesterol homeostasis independent of weight loss.