Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice
Year: 2021
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: American Diabetes Association, Children's Hospital Los Angeles, University of Michigan, Novo Nordisk, China Scholarship Council, National Institutes of Health, University of Michigan Center for Gastrointestinal Research, Michigan Diabetes Research Center, University of Michigan, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences
Awards: Mechanisms by which adipocytes adapt to cool environmental temperatures, University of Michigan Center for Gastrointestinal Research, G142261553, National Metabolomics Data Repository - nextgen Metabolomics Workbench, G1849614181, Interdisciplinary study of marrow adiposity, mineral metabolism,and energy balanc, G1923858223, G2049072053, Michigan Diabetes Research and Training Center, Interdisciplinary Study of Marrow Adiposity, Mineral Metabolism, and Energy Balance, G2287564986, Michigan Mouse Metabolic Phenotyping Center, G2549679456, Michigan Regional Comprehensive Metabolomics Resource Core (MRC2), G2757709669, Bone Robustness as a Biomarker of Skeletal Aging and Fragility, A novel paracrine role for GLP-1 in the islet, G3744167026, G4112104809, G4133317455, G5544006853, G5577612281, Obesity & Gastrointestinal Surgery Research Training Program, G5878780909, GENETIC DETERMINATION OF SKELETAL FRAGILITY, Mechanisms of Post-Bariatric Hypoglycemia, Michigan Institute for Clinical and Health Research (MICHR), G7171616477, G729200540, G779270570, G8809292834, Genetic Determination of Skeletal Fragility, G9000075728, G9000090783, G9000097295, G9000101265, G9000219159, G9000231952, G9000242564, G9000299033, G9000301509, Michigan Integrative Musculoskeletal Health Core Center (Overall Application), Michigan Diabetes Research Center (MDRC), Developmental Origins of Metabolic Disorders, Michigan Nutrition Obesity Research Center
OpenAlex ID: W3189044466