The anti-obesity effect of FGF19 does not require UCP1-dependent thermogenesis

التفاصيل البيبلوغرافية
العنوان: The anti-obesity effect of FGF19 does not require UCP1-dependent thermogenesis
المؤلفون: Patrick J. Antonellis, James W. Perfield, Brian A. Droz, Tamer Coskun, Richard Cosgrove, Tara E. Chouinard, Andrew C. Adams, Steven M. Bauer, Mark R. Wade, Libbey S. O’Farrell, Ricardo J. Samms, Joseph T. Brozinick
المصدر: Molecular Metabolism
Molecular Metabolism, Vol 30, Iss, Pp 131-139 (2019)
سنة النشر: 2019
مصطلحات موضوعية: 0301 basic medicine, Male, CYP7A1, Adipose tissue, Mice, Obese, FGF19, Mice, 0302 clinical medicine, Adipose Tissue, Brown, Brown adipose tissue, Uncoupling Protein 1, Mice, Knockout, Bile acid, Chemistry, Thermogenesis, Thermogenin, Mitochondria, medicine.anatomical_structure, medicine.medical_specialty, lcsh:Internal medicine, UCP1, medicine.drug_class, Adipose Tissue, White, 030209 endocrinology & metabolism, Cholesterol 7 alpha-hydroxylase, Brief Communication, Diet, High-Fat, Diabetes Mellitus, Experimental, Mitochondrial Proteins, 03 medical and health sciences, Internal medicine, medicine, Animals, Obesity, lcsh:RC31-1245, Molecular Biology, Lipogenesis, Body Weight, BAT, Lipid metabolism, Cell Biology, Lipid Metabolism, Fibroblast Growth Factors, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Metabolic, Insulin Resistance, Energy Metabolism
الوصف: Objective Fibroblast growth factor 19 (FGF19) is a postprandial hormone which plays diverse roles in the regulation of bile acid, glucose, and lipid metabolism. Administration of FGF19 to obese/diabetic mice lowers body weight, improves insulin sensitivity, and enhances glycemic control. The primary target organ of FGF19 is the liver, where it regulates bile acid homeostasis in response to nutrient absorption. In contrast, the broader pharmacologic actions of FGF19 are proposed to be driven, in part, by the recruitment of the thermogenic protein uncoupling protein 1 (UCP1) in white and brown adipose tissue. However, the precise contribution of UCP1-dependent thermogenesis to the therapeutic actions of FGF19 has not been critically evaluated. Methods Using WT and germline UCP1 knockout mice, the primary objective of the current investigation was to determine the in vivo pharmacology of FGF19, focusing on its thermogenic and anti-obesity activity. Results We report that FGF19 induced mRNA expression of UCP1 in adipose tissue and show that this effect is required for FGF19 to increase caloric expenditure. However, we demonstrate that neither UCP1 induction nor an elevation in caloric expenditure are necessary for FGF19 to induce weight loss in obese mice. In contrast, the anti-obesity action of FGF19 appeared to be associated with its known physiological role. In mice treated with FGF19, there was a significant reduction in the mRNA expression of genes associated with hepatic bile acid synthesis enzymes, lowered levels of hepatic bile acid species, and a significant increase in fecal energy content, all indicative of reduced lipid absorption in animals treated with FGF19. Conclusion Taken together, we report that the anti-obesity effect of FGF19 occurs in the absence of UCP1. Our data suggest that the primary way in which exogenous FGF19 lowers body weight in mice may be through the inhibition of bile acid synthesis and subsequently a reduction of dietary lipid absorption.
Highlights • FGF19 increases UCP1 transcription in adipose tissue and is associated with significant weight loss. • The increase in metabolic rate observed with FGF19 is dependent upon the presence of UCP1. • In the absence of UCP1, the anti-obesity effect of FGF19 are associated with a greater reduction in energy absorption.
تدمد: 2212-8778
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f3a672ee97f46b2f383c07d191a28e6Test
https://pubmed.ncbi.nlm.nih.gov/31767164Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....0f3a672ee97f46b2f383c07d191a28e6
قاعدة البيانات: OpenAIRE