Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations

Justin A. Fletcher, Melissa A. Linden, Ryan D. Sheldon, Grace M. Meers, E. Matthew Morris, Anthony Butterfield, James W. Perfield, John P. Thyfault, R. Scott Rector

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)G832-G843
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume310
Issue number10
DOIs
StatePublished - May 2016
Externally publishedYes

Fingerprint

Knockout Mice
Liver
Adiposity
Palmitates
Running
Triglycerides
Body Weight
fibroblast growth factor 21
Insulin
Messenger RNA
AMP-Activated Protein Kinases
Hyperinsulinism
Coenzyme A
Serum
Nonesterified Fatty Acids
Oxidoreductases
Cholesterol
Genotype
Phosphorylation
Glucose

Keywords

  • Exercise
  • Metabolism
  • Mitochondria
  • Mitochondrial function

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations. / Fletcher, Justin A.; Linden, Melissa A.; Sheldon, Ryan D.; Meers, Grace M.; Morris, E. Matthew; Butterfield, Anthony; Perfield, James W.; Thyfault, John P.; Rector, R. Scott.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 310, No. 10, 05.2016, p. G832-G843.

Research output: Contribution to journalArticle

Fletcher, JA, Linden, MA, Sheldon, RD, Meers, GM, Morris, EM, Butterfield, A, Perfield, JW, Thyfault, JP & Rector, RS 2016, 'Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 310, no. 10, pp. G832-G843. https://doi.org/10.1152/ajpgi.00355.2015
Fletcher, Justin A. ; Linden, Melissa A. ; Sheldon, Ryan D. ; Meers, Grace M. ; Morris, E. Matthew ; Butterfield, Anthony ; Perfield, James W. ; Thyfault, John P. ; Rector, R. Scott. / Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2016 ; Vol. 310, No. 10. pp. G832-G843.
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