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

Nat Commun. 2021 Aug 6;12(1):4768. doi: 10.1038/s41467-021-24914-y.


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 (FGF15INT-KO) mice which were maintained on high-fat diet. FGF15INT-KO mice lost more weight after VSG as a result of increased lean tissue loss. FGF15INT-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 FGF15INT-KO. VSG resulted in increased plasma bile acid levels but were considerably higher in VSG-FGF15INT-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue
  • Animals
  • Bariatric Surgery
  • Bile Acids and Salts / blood
  • Blood Glucose
  • Bone Density
  • Bone Marrow
  • Diabetes Mellitus, Type 2
  • Diet, High-Fat
  • Disease Models, Animal
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology*
  • Gastrectomy / adverse effects*
  • Glucose Tolerance Test
  • Homeostasis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / surgery
  • Weight Loss


  • Bile Acids and Salts
  • Blood Glucose
  • fibroblast growth factor 15, mouse
  • Fibroblast Growth Factors