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

Autor: Bozadjieva-Kramer N; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Shin JH; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Shao Y; Center for Obesity and Metabolic Surgery, Huashan Hospital of Fudan University, Shanghai, China., Gutierrez-Aguilar R; Divsión de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México and Laboratorio de Enfermedades Metabólicas: Obesidad y Diabetes, Hospital Infantil de México 'Federico Gómez', Mexico, Mexico., Li Z; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Heppner KM; Novo Nordisk Research Center Seattle, Inc, Seattle, WA, USA., Chiang S; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Vargo SG; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Granger K; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Sandoval DA; Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., MacDougald OA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Seeley RJ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA. seeleyrj@med.umich.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Aug 06; Vol. 12 (1), pp. 4768. Date of Electronic Publication: 2021 Aug 06.
DOI: 10.1038/s41467-021-24914-y
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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