title: Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice.
abstract: 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 shown to 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 metabolic improvements whereas GH transgenic mice resisted most of the beneficial effects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its effects mostly 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. The resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneficial effects of FGF21.
authors.affiliation: Division of Geriatrics Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9628, USA ; Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9636, USA ; Department of Biochemistry, Panjab University, Chandigarh 160014, India.
authors.forename: Ravneet K
authors.initials: RK
authors.lastname: Boparai
authors.affiliation: Division of Geriatrics Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9628, USA.
authors.forename: Oge
authors.initials: O
authors.lastname: Arum
authors.affiliation: Division of Geriatrics Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9628, USA ; IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Johanna G
authors.initials: JG
authors.lastname: Miquet
authors.affiliation: Division of Geriatrics Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9628, USA ; Burnett School of Biomedical Sciences, University of Central Florida, 6900 Lake Nona Boulevard, Orlando, FL 32827, USA ; Department of Head and Neck Surgery, The Greater Poland Cancer Centre, 15 Garbary Street, 61-866 Poznan, Poland.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
authors.affiliation: Division of Geriatrics Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9628, USA.
authors.forename: Andrzej
authors.identifier: 0000-0002-2569-557X
authors.initials: A
authors.lastname: Bartke
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794-9636, USA ; Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA 23510, USA.
authors.forename: Romesh K
authors.initials: RK
authors.lastname: Khardori