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

Autor: Yikai Shao, Ormond A. MacDougald, Katrina Granger, Darleen A. Sandoval, Kristy M. Heppner, Jae Hoon Shin, Ziru Li, Ruth Gutierrez-Aguilar, Samuel Chiang, Sara G. Vargo, Randy J. Seeley, Nadejda Bozadjieva-Kramer
Rok vydání: 2021
Předmět:
Blood Glucose
Male
medicine.medical_specialty
Sleeve gastrectomy
medicine.drug_class
Science
medicine.medical_treatment
Bariatric Surgery
General Physics and Astronomy
Adipose tissue
Type 2 diabetes
Diet
High-Fat
Article
General Biochemistry
Genetics and Molecular Biology
Energy homeostasis
Bile Acids and Salts
Mice
Bone Density
Bone Marrow
Gastrectomy
Internal medicine
Weight Loss
parasitic diseases
medicine
Animals
Homeostasis
Obesity
Gastrointestinal hormones
Mice
Knockout
Multidisciplinary
Bile acid
business.industry
FGF15
Metabolic diseases
General Chemistry
Glucose Tolerance Test
medicine.disease
Bone quality and biomechanics
Fibroblast Growth Factors
Mice
Inbred C57BL
Disease Models
Animal
medicine.anatomical_structure
Endocrinology
Adipose Tissue
Diabetes Mellitus
Type 2
Bone marrow
business
Hormone
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-19 (2021)
ISSN: 2041-1723
Popis: 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.
The mechanisms that mediate the effects of weight loss surgeries such as vertical sleeve gastrectomy (VSG) are incompletely understood. Here the authors show that intestinal FGF15 is necessary to improve glucose tolerance and to prevent the loss of muscle and bone mass after VSG, potentially via protection against bile acid toxicity.
Databáze: OpenAIRE
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