Fibroblast growth factor 21 (FGF21) therapy attenuates left ventricular dysfunction and metabolic disturbance by improving FGF21 sensitivity, cardiac mitochondrial redox homoeostasis and structural changes in pre‐diabetic rats. (20th May 2016)

• Record Type: Journal Article
• Authors: Tanajak, P.; Sa‐nguanmoo, P.; Wang, X.; Liang, G.; Li, X.; Jiang, C.; Chattipakorn, S. C.; Chattipakorn, N.
• Is Part Of: Acta physiologica. Volume 217:Number 4(2016)
• Page Start: 287
• Page End: 299
• Publication Date: 2016-05-20
• Subjects: cardiac function -- fatty acid β‐oxidation -- fibroblast growth factor 21 (FGF21) -- FGF21 resistance -- mitochondria -- obesity–insulin resistance; Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12698
• Languages: English
• ISSNs: 1748-1708

Abstract

Abstract: Aims: Fibroblast growth factor 21 (FGF21) acts as a metabolic regulator and exerts cardioprotective effects. However, the effects of long‐term FGF21 administration on the heart under the FGF21‐resistant condition in obese, insulin‐resistant rats have not been investigated. We hypothesized that long‐term FGF21 administration reduces FGF21 resistance and insulin resistance and attenuates cardiac dysfunction in obese, insulin‐resistant rats. Methods: Eighteen rats were fed on either a normal diet ( n = 6) or a high‐fat diet (HFD; n = 12) for 12 weeks. Then, rats in the HFD group were divided into two subgroups ( n = 6 per subgroup) and received either the vehicle (HFV) or recombinant human FGF21 (rhFGF21, 0.1 mg kg −1 day −1 ; HFF) injected intraperitoneally for 28 days. The metabolic parameters, inflammation, malondialdehyde (MDA), heart rate variability (HRV), left ventricular (LV) function, cardiac mitochondrial redox homoeostasis, cardiac mitochondrial fatty acid β ‐oxidation (FAO) and anti‐apoptotic signalling pathways were determined. Results: HFV rats had increased dyslipidaemia, insulin resistance, plasma FGF21 levels, TNF‐ α, adiponectin and MDA, depressed HRV, and impaired LV and mitochondrial function. HFV rats also had decreased cardiac Bcl‐2, cardiac PGC‐1 α and CPT‐1 protein expression. However, FGF21 restored metabolic parameters, decreased TNF‐ α and MDA, increased serum adiponectin, and improved HRV, cardiac mitochondrial and LV function in HFF rats. Moreover, HFF rats had increased cardiac Bcl‐2, cardiac PGC‐1 α and CPT‐1 protein expression. Conclusion: Long‐term FGF21 therapy attenuates FGF21 resistance and insulin resistance and exerts cardioprotection by improving cardiometabolic regulation via activating anti‐apoptotic and cardiac mitochondrial FAO signalling pathways in obese, insulin‐resistant rats.