Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice

Abstract

Bariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive but provide the most effective improvements in obesity and Type 2 diabetes. We hypothesized a potential role for the gut hormone Fibroblast-Growth Factor 15/19 which is increased after VSG and pharmacologically can improve energy homeostasis and glucose handling. We generated intestinal-specific FGF15 knockout (FGF15^INT-KO) mice which were maintained on high-fat diet. FGF15^INT-KO mice lost more weight after VSG as a result of increased lean tissue loss. FGF15^INT-KO mice also lost more bone density and bone marrow adipose tissue after VSG. The effect of VSG to improve glucose tolerance was also absent in FGF15^INT-KO. VSG resulted in increased plasma bile acid levels but were considerably higher in VSG-FGF15^INT-KO mice. These data point to an important role after VSG for intestinal FGF15 to protect the organism from deleterious effects of VSG potentially by limiting the increase in circulating bile acids.

The mechanisms that mediate the effects of weight loss surgeries such as vertical sleeve gastrectomy (VSG) are incompletely understood. Here the authors show that intestinal FGF15 is necessary to improve glucose tolerance and to prevent the loss of muscle and bone mass after VSG, potentially via protection against bile acid toxicity.