| Autor: |
Le, Thao D. V., Fathi, Payam, Watters, Amanda B., Ellis, Blair J., Bozadjieva-Kramer, Nadejda, Perez, Misty B., Sullivan, Andrew I., Rose, Jesse P., Baggio, Laurie L., Koehler, Jacqueline, Brown, Jennifer L., Bales, Michelle B., Nwaba, Kaitlyn G., Campbell, Jonathan E., Drucker, Daniel J., Potthoff, Matthew J., Seeley, Randy J., Ayala, Julio E. |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
bioRxiv |
| Popis: |
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 liverFgf21expression 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 liverFgf21knockout (LivFgf21-/-) mice fed calorically matched diets with low- (LC) or high-carbohydrate (HC) content, we found that only HC-fed LivFgf21-/-mice were resistant to liraglutide-induced weight loss. Similarly, liraglutide-induced weight loss was partially impaired in LivFgf21-/-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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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