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

N Bozadjieva-Kramer, JH Shin, Y Shao… - Nature …, 2021 - nature.com
N Bozadjieva-Kramer, JH Shin, Y Shao, R Gutierrez-Aguilar, Z Li, KM Heppner, S Chiang…
Nature Communications, 2021nature.com
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 …
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 (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.
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