Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice.

BOPARAI RK; OGE A; MIQUET JG; MASTERNAK MM; BARTKE A; KHARDORI RK

International journal of endocrinology

Hindawi Publishing Corporation

Lugar: New York; Año: 2015

Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shownto inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used. Expectedly, in response to FGF21 treatment control littermates showed metabolicimprovements whereas GH transgenic mice resisted most of the beneicial efects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its efectsmostly at the transcriptional level,we analyzed and observed significant upregulation in expression of various genes involved in carbohydrate and lipid metabolism, energy homeostasis, and antioxidant defense in FGF21-treated controls, but not in GH transgenics. he resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneicial efects of FGF21.