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Impact of liver PGC-1α on exercise and exercise training-induced regulation of hepatic autophagy and mitophagy in mice on HFF.
Physiol Rep 2018; 6(13):e13731PR

Abstract

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.

Authors+Show Affiliations

Department of Biology, Section for Cell Biology and Physiology, University of Copenhagen, Kobenhavn, Denmark.Department of Biology, Section for Cell Biology and Physiology, University of Copenhagen, Kobenhavn, Denmark.Department of Biology, Section for Cell Biology and Physiology, University of Copenhagen, Kobenhavn, Denmark.Department of Biology, Section for Cell Biology and Physiology, University of Copenhagen, Kobenhavn, Denmark.Department of Biology, Section for Cell Biology and Physiology, University of Copenhagen, Kobenhavn, Denmark.Department of Biology, Section for Cell Biology and Physiology, University of Copenhagen, Kobenhavn, Denmark.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29962089

Citation

Dethlefsen, Maja M., et al. "Impact of Liver PGC-1α On Exercise and Exercise Training-induced Regulation of Hepatic Autophagy and Mitophagy in Mice On HFF." Physiological Reports, vol. 6, no. 13, 2018, pp. e13731.
Dethlefsen MM, Kristensen CM, Tøndering AS, et al. Impact of liver PGC-1α on exercise and exercise training-induced regulation of hepatic autophagy and mitophagy in mice on HFF. Physiol Rep. 2018;6(13):e13731.
Dethlefsen, M. M., Kristensen, C. M., Tøndering, A. S., Lassen, S. B., Ringholm, S., & Pilegaard, H. (2018). Impact of liver PGC-1α on exercise and exercise training-induced regulation of hepatic autophagy and mitophagy in mice on HFF. Physiological Reports, 6(13), pp. e13731. doi:10.14814/phy2.13731.
Dethlefsen MM, et al. Impact of Liver PGC-1α On Exercise and Exercise Training-induced Regulation of Hepatic Autophagy and Mitophagy in Mice On HFF. Physiol Rep. 2018;6(13):e13731. PubMed PMID: 29962089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of liver PGC-1α on exercise and exercise training-induced regulation of hepatic autophagy and mitophagy in mice on HFF. AU - Dethlefsen,Maja M, AU - Kristensen,Caroline M, AU - Tøndering,Anna S, AU - Lassen,Signe B, AU - Ringholm,Stine, AU - Pilegaard,Henriette, PY - 2018/03/21/received PY - 2018/05/07/revised PY - 2018/05/08/accepted PY - 2018/7/3/entrez PY - 2018/7/3/pubmed PY - 2019/9/5/medline KW - Acute exercise KW - Liver PGC-1α KO KW - autophagy KW - exercise training KW - high-fat high-fructose KW - liver KW - mitophagy SP - e13731 EP - e13731 JF - Physiological reports JO - Physiol Rep VL - 6 IS - 13 N2 - 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. SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/29962089/Impact_of_liver_PGC_1α_on_exercise_and_exercise_training_induced_regulation_of_hepatic_autophagy_and_mitophagy_in_mice_on_HFF_ L2 - https://doi.org/10.14814/phy2.13731 DB - PRIME DP - Unbound Medicine ER -