Von Schulze 2018 J Physiol
| Von Schulze A, McCoin CS, Onyekere C, Allen J, Geiger P, Dorn GW, Morris EM, Thyfault JP (2018) Hepatic mitochondrial adaptations to physical activity: impact of sexual dimorphism, PGC1Ξ±, and BNIP3 mediated mitophagy. J Physiol [Epub ahead of print]. |
Von Schulze A, McCoin CS, Onyekere C, Allen J, Geiger P, Dorn GW, Morris EM, Thyfault JP (2018) J Physiol
Abstract: Hepatic mitochondrial adaptations to physical activity may be regulated by biogenesis- and mitophagy-associated pathways in a sex-dependent manner. Here, we tested if mice with targeted deficiencies in liver-specific peroxisome proliferator-activated receptor Ξ³ coactivator 1Ξ± (PGC1Ξ±; LPGC1Ξ±+/-) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)-mediated mitophagy (BNIP3-/-) would have reduced physical activity-induced adaptations in respiratory capacity, H2 O2 emission and mitophagy compared to wild-type (WT) controls and if these effects were impacted by sex. Male and female WT, LPGC1Ξ±+/- and BNIP3-/- C57BL6/J mice were divided into groups that remained sedentary or had access to daily physical activity via voluntary wheel running (VWR) (n = 6-10/group) for 4 weeks. Mice had ad libitum access to low-fat diet and water. VWR reduced basal mitochondrial respiration, increased mitochondrial coupling and altered ubiquitin-mediated mitophagy in a sex-specific manner in WT mice. Female mice of all genotypes displayed higher electron transport system content, displayed increased ADP-stimulated respiration, produced less mitochondrially derived reactive oxygen species, exhibited reduced mitophagic flux, and were less responsive to VWR compared to males. Males responded more robustly to VWR-induced changes in hepatic mitochondrial function resulting in a match to adaptations found in females. Deficiencies in PGC1Ξ± and BNIP3 alone did not largely alter mitochondrial adaptations to VWR. However, VWR restored sex-dependent abnormalities in mitophagic flux in LPGC1Ξ±+/-. Finally, BNIP3-/- mice had elevated mitochondrial content and increased mitochondrial respiration putatively through repressed mitophagic flux. In conclusion, hepatic mitochondrial adaptations to physical activity are more dependent on sex than PGC1Ξ± and BNIP3.
Β© 2018 The Authors. The Journal of Physiology Β© 2018 The Physiological Society. β’ Keywords: Exercise, Female, Liver, Metabolism, Mitochondrial respiratory capacity, Reactive oxygen species, Steatosis β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US KS Kansas City Thyfault JP
Labels: MiParea: Respiration, Genetic knockout;overexpression, Gender, Exercise physiology;nutrition;life style
Organism: Mouse
Tissue;cell: Liver
Preparation: Isolated mitochondria
Coupling state: OXPHOS, ET
Pathway: F, N, NS
HRR: Oxygraph-2k
Labels, 2018-08
