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

Nadejda Bozadjieva-Kramer, Jae Hoon Shin, Yikai Shao, Ruth Gutierrez-Aguilar, Ziru Li, Kristy M. Heppner, Samuel Chiang, Sara G. Vargo, Katrina Granger, Darleen A. Sandoval, Ormond A. MacDougald and Randy J. Seeley ()
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Nadejda Bozadjieva-Kramer: University of Michigan
Jae Hoon Shin: University of Michigan
Yikai Shao: Huashan Hospital of Fudan University
Ruth Gutierrez-Aguilar: Universidad Nacional Autónoma de México and Laboratorio de Enfermedades Metabólicas: Obesidad y Diabetes, Hospital Infantil de México “Federico Gómez”
Ziru Li: University of Michigan
Kristy M. Heppner: Novo Nordisk Research Center Seattle, Inc
Samuel Chiang: University of Michigan
Sara G. Vargo: University of Michigan
Katrina Granger: University of Michigan
Darleen A. Sandoval: University of Colorado Anschutz Medical Campus
Ormond A. MacDougald: University of Michigan
Randy J. Seeley: University of Michigan

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24914-y

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