Open AccessImpact of liver PGC‐1α on exercise and exercise training‐induced regulation of hepatic autophagy and mitophagy in mice on HFF
Author(s) -
Dethlefsen Maja M.,
Kristensen Caroline M.,
Tøndering Anna S.,
Lassen Signe B.,
Ringholm Stine,
Pilegaard Henriette
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13731
Subject(s) - mitophagy , autophagy , steatosis , medicine , endocrinology , aerobic exercise , endurance training , chemistry , apoptosis , biochemistry
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.