Sex modulates hepatic mitochondrial adaptations to high-fat diet and physical activity
| Autor: | Kartik Shankar, Alex T. Von Schulze, John P. Thyfault, Devin C. Koestler, Claire J. Houchen, Julie Allen, Qing Xia, Gerald W. Dorn nd, E. Matthew Morris, Adrianna Maurer, Kelly N. Z. Fuller, Colin S. McCoin |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Physical Exertion Physical activity Mitochondria Liver 030209 endocrinology & metabolism Biology Diet High-Fat Mitochondrial Proteins Mice 03 medical and health sciences Oxygen Consumption 0302 clinical medicine Non-alcoholic Fatty Liver Disease Physical Conditioning Animal Physiology (medical) Internal medicine Mitophagy medicine Animals Diet Fat-Restricted Mice Knockout chemistry.chemical_classification Sex Characteristics Reactive oxygen species digestive oral and skin physiology nutritional and metabolic diseases Membrane Proteins food and beverages High fat diet Metabolism medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mice Inbred C57BL Sexual dimorphism 030104 developmental biology Endocrinology Gene Expression Regulation chemistry Female Sedentary Behavior Steatosis Research Article |
| Zdroj: | Am J Physiol Endocrinol Metab |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | The impact of sexual dimorphism and mitophagy on hepatic mitochondrial adaptations during the treatment of steatosis with physical activity are largely unknown. Here, we tested if deficiencies in liver-specific peroxisome proliferative activated-receptor-γ coactivator-1α (PGC-1α), a transcriptional coactivator of biogenesis, and BCL-2/ADENOVIRUS EIB 19-kDa interacting protein (BNIP3), a mitophagy regulator, would impact hepatic mitochondrial adaptations (respiratory capacity, H2O2production, mitophagy) to a high-fat diet (HFD) and HFD plus physical activity via voluntary wheel running (VWR) in both sexes. Male and female wild-type (WT), liver-specific PGC-1α heterozygote (LPGC-1α), and BNIP3 null mice were thermoneutral housed (29–31°C) and divided into three groups: sedentary-low-fat diet (LFD), 16 wk of (HFD), or 16 wk of HFD with VWR for the final 8 wk (HFD + VWR) ( n = 5–7/sex/group). HFD did not impair mitochondrial respiratory capacity or coupling in any group; however, HFD + VWR significantly increased maximal respiratory capacity only in WT and PGC-1α females. Males required VWR to elicit mitochondrial adaptations that were inherently present in sedentary females including greater mitochondrial coupling control and reduced H2O2production. Females had overall reduced markers of mitophagy, steatosis, and liver damage. Steatosis and markers of liver injury were present in sedentary male mice on the HFD and were effectively reduced with VWR despite no resolution of steatosis. Overall, reductions in PGC-1α and loss of BNIP3 only modestly impacted mitochondrial adaptations to HFD and HFD + VWR with the biggest effect seen in BNIP3 females. In conclusion, hepatic mitochondrial adaptations to HFD and treatment of HFD-induced steatosis with VWR are more dependent on sex than PGC-1α or BNIP3. |
| Databáze: | OpenAIRE |
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