التفاصيل البيبلوغرافية
| العنوان: |
Liver Fibroblast Growth Factor 21 (FGF21) is Required for the Full Anorectic Effect of the Glucagon-Like Peptide-1 Receptor Agonist Liraglutide in Male Mice fed High Carbohydrate Diets. |
| المؤلفون: |
Le TDV, Fathi P, Watters AB, Ellis BJ, Bozadjieva-Kramer N, Perez MB, Sullivan AI, Rose JP, Baggio LL, Koehler J, Brown JL, Bales MB, Nwaba KG, Campbell JE, Drucker DJ, Potthoff MJ, Seeley RJ, Ayala JE |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 03. Date of Electronic Publication: 2023 Jan 03. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Glucagon-like peptide-1 receptor (GLP-1R) agonists and fibroblast growth factor 21 (FGF21) confer similar metabolic benefits. Studies report that GLP-1RA induce FGF21. Here, we investigated the mechanisms engaged by the GLP-1R agonist liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21. We show that liraglutide increases FGF21 levels via neuronal GLP-1R activation. We also demonstrate that lack of liver Fgf21 expression confers partial resistance to liraglutide-induced weight loss. Since FGF21 reduces carbohydrate intake, we tested whether the contribution of FGF21 to liraglutide-induced weight loss is dependent on dietary carbohydrate content. In control and liver Fgf21 knockout (Liv Fgf21 -/- ) mice fed calorically matched diets with low- (LC) or high-carbohydrate (HC) content, we found that only HC-fed Liv Fgf21 -/- mice were resistant to liraglutide-induced weight loss. Similarly, liraglutide-induced weight loss was partially impaired in Liv Fgf21 -/- mice fed a high-fat, high-sugar (HFHS) diet. Lastly, we show that loss of neuronal β-klotho expression also diminishes liraglutide-induced weight loss in mice fed a HC or HFHS diet, indicating that FGF21 mediates liraglutide-induced weight loss via neuronal FGF21 action. Our findings support a novel role for a GLP-1R-FGF21 axis in regulating body weight in the presence of high dietary carbohydrate content. |
| التعليقات: |
Update in: Mol Metab. 2023 Apr 6;:101718. (PMID: 37030441) |
| تواريخ الأحداث: |
Date Created: 20230130 Latest Revision: 20230414 |
| رمز التحديث: |
20230415 |
| مُعرف محوري في PubMed: |
PMC9881863 |
| DOI: |
10.1101/2023.01.03.522509 |
| PMID: |
36711605 |
| قاعدة البيانات: |
MEDLINE |
