Impact of liver PGC-1α on exercise and exercise training-induced regulation of hepatic autophagy and mitophagy in mice on HFF

Physiol Rep. 2018 Jul;6(13):e13731. doi: 10.14814/phy2.13731.


Hepatic autophagy has been shown to be regulated by acute exercise and exercise training. Moreover, high-fat diet-induced steatosis has been reported to be associated with impaired hepatic autophagy. In addition, autophagy has been shown to be regulated by acute exercise and exercise training in a PGC-1α dependent manner in skeletal muscle. The aim of this study was to test the hypotheses that high-fat high-fructose (HFF) diet changes hepatic autophagy and mitophagy, that exercise training can restore this through a PGC-1α-mediated mechanism, and that acute exercise regulates autophagy and mitophagy in the liver. Liver samples were obtained from liver-specific PGC-1α KO mice and their littermate Lox/Lox mice fed a HFF diet or a control diet for 13 weeks. The HFF mice were either exercise trained (ExT) on a treadmill the final 5 weeks or remained sedentary (UT). In addition, half of each group performed at the end of the intervention an acute 1 h exercise bout. HFF resulted in increased hepatic BNIP3 dimer and Parkin protein, while exercise training increased BNIP3 total protein without affecting the elevated BNIP3 dimer protein. In addition, exercise training reversed a HFF-induced increase in hepatic LC3II/LC3I protein ratio, as well as a decreased PGC-1α mRNA level. Acute exercise increased hepatic PGC-1α mRNA in HFF UT mice only. In conclusion, this indicates that exercise training in part reverses a HFF-induced increase in hepatic autophagy and capacity for mitophagy in a PGC-1α-independent manner. Moreover, HFF may blunt acute exercise-induced regulation of hepatic autophagy.

Keywords: Acute exercise; Liver PGC-1α KO; autophagy; exercise training; high-fat high-fructose; liver; mitophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Dietary Sugars / pharmacology
  • Fructose / pharmacology
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mitophagy*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Physical Conditioning, Animal*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism


  • BNip3 protein, mouse
  • Dietary Sugars
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Fructose
  • Ubiquitin-Protein Ligases
  • parkin protein

Associated data

  • GENBANK/ab56416