Vertical Sleeve Gastrectomy Restores Glucose Homeostasis in Apolipoprotein A-Ⅳ KO Mice

摘要

Bariatric surgery is the most successful strategy for treating obesity, yet the mechanisms for this success are not clearly understood. Clinical literature suggests that plasma levels of apolipoprotein A-Ⅳ (apoA-Ⅳ) rise with Roux-en-Y gastric bypass (RYGB). apoA-Ⅳ is secreted from the intestine postprandially and has demonstrated benefits for both glucose and lipid homeostasis. Because of the parallels in the metabolic improvements seen with surgery and the rise in apoA-Ⅳ levels, we hypothesized that apoA-Ⅳ was necessary for obtaining the metabolic benefits of bariatric surgery. To test this hypothesis, we performed vertical sleeve gastrectomy (VSG), a surgery with clinical efficacy very similar to that for RYGB, in whole-body apoA-Ⅳ knockout (KO) mice. We found that VSG reduced body mass and improved both glucose and lipid homeostasis similarly in wild-type mice compared with apoA-Ⅳ KO mice. In fact, VSG normalized the impairment in glucose tolerance and caused a significantly greater improvement in hepatic triglyceride storage in the apoA-Ⅳ KO mice. Last, independent of surgery, apoA-Ⅳ KO mice had a significantly reduced preference for a high-fat diet. Altogether, these data suggest that apoA-Ⅳ is not necessary for the metabolic improvements shown with VSG, but also suggest an interesting role for apoA-Ⅳ in regulating macronutrient preference and hepatic triglyceride levels. Future studies are necessary to determine whether this is the case for RYGB as well.