TY - JOUR
T1 - Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations
AU - Fletcher, Justin A.
AU - Linden, Melissa A.
AU - Sheldon, Ryan D.
AU - Meers, Grace M.
AU - Morris, E. Matthew
AU - Butterfield, Anthony
AU - Perfield, James W.
AU - Thyfault, John P.
AU - Rector, R. Scott
N1 - Funding Information:
This research was supported by an ACSM Foundation Research Grant from the American College of Sports Medicine Foundation (J. A. Fletcher), as well as National Institutes of Health Grants T32 AR 048523-07 (J. A. Fletcher and E. M. Morris) and DK-088940 (J. P. Thyfault) and Veterans Affairs Grants Merit (1I01BX002567-01, J. P. Thyfault) and VHA-CDA2 IK2BX001299 (R. S. Rector).
Publisher Copyright:
© 2016, American Physiological Society. All rights reserved.
PY - 2016/5
Y1 - 2016/5
N2 - Exercise stimulates hepatic mitochondrial adaptations; however, the mechanisms remain largely unknown. Here we tested whether FGF21 plays an obligatory role in exercise induced hepatic mitochondrial adaptations by testing exercise responses in FGF21 knockout mice. FGF21 knockout (FGF21-KO) and wild-type (WT) mice (11–12 wk of age) had access to voluntary running wheels for exercise (EX) or remained sedentary for 8 wk. FGF21 deficiency resulted in greater body weight, adiposity, serum cholesterol, insulin, and glucose concentrations compared with WT mice (P < 0.05). In addition, hepatic mitochondrial complete palmitate oxidation, β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity, and nuclear content of PGC-1α were 30–50% lower in FGF21-KO mice compared with WT mice (P < 0.01). EX effectively lowered body weight, adiposity, serum triglycerides, free fatty acids, and insulin and normalized mitochondrial complete palmitate oxidation in the FGF21-KO mice, whereas the reduced hepatic β-HAD activity and lowered nuclear content of PGC-1α in FGF21-KO mice were not restored by EX. In addition, EX increased hepatic CPT-1α mRNA expression and ACC phosphorylation (a marker of increased AMPK activity) and reduced hepatic triacylglycerol content in both genotypes. However, FGF21-KO mice displayed a lower EX-induced increase in the mRNA expression of the hepatic gluconeogenic gene, PEPCK, compared with WT. In conclusion, FGF21 does not appear necessary for exercise-induced systemic and hepatic mitochondrial adaptations, but the increased adiposity, hyperinsulinemia, and impairments in hepatic mitochondrial function induced by FGF21 deficiency can be partially rescued by daily wheel running exercise.
AB - Exercise stimulates hepatic mitochondrial adaptations; however, the mechanisms remain largely unknown. Here we tested whether FGF21 plays an obligatory role in exercise induced hepatic mitochondrial adaptations by testing exercise responses in FGF21 knockout mice. FGF21 knockout (FGF21-KO) and wild-type (WT) mice (11–12 wk of age) had access to voluntary running wheels for exercise (EX) or remained sedentary for 8 wk. FGF21 deficiency resulted in greater body weight, adiposity, serum cholesterol, insulin, and glucose concentrations compared with WT mice (P < 0.05). In addition, hepatic mitochondrial complete palmitate oxidation, β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity, and nuclear content of PGC-1α were 30–50% lower in FGF21-KO mice compared with WT mice (P < 0.01). EX effectively lowered body weight, adiposity, serum triglycerides, free fatty acids, and insulin and normalized mitochondrial complete palmitate oxidation in the FGF21-KO mice, whereas the reduced hepatic β-HAD activity and lowered nuclear content of PGC-1α in FGF21-KO mice were not restored by EX. In addition, EX increased hepatic CPT-1α mRNA expression and ACC phosphorylation (a marker of increased AMPK activity) and reduced hepatic triacylglycerol content in both genotypes. However, FGF21-KO mice displayed a lower EX-induced increase in the mRNA expression of the hepatic gluconeogenic gene, PEPCK, compared with WT. In conclusion, FGF21 does not appear necessary for exercise-induced systemic and hepatic mitochondrial adaptations, but the increased adiposity, hyperinsulinemia, and impairments in hepatic mitochondrial function induced by FGF21 deficiency can be partially rescued by daily wheel running exercise.
KW - Exercise
KW - Metabolism
KW - Mitochondria
KW - Mitochondrial function
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U2 - 10.1152/ajpgi.00355.2015
DO - 10.1152/ajpgi.00355.2015
M3 - Article
C2 - 27012775
AN - SCOPUS:84984598816
SN - 0193-1857
VL - 310
SP - G832-G843
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 10
ER -