title: Effect of exercise on mouse liver and brain bioenergetic infrastructures.
abstract: To assess the effects of exercise on liver and brain bioenergetic infrastructures, we exposed C57BL/6 mice to 6 weeks of moderate-intensity treadmill exercise. During the training period, fasting blood glucose was lower in exercised mice than in sedentary mice, but serum insulin levels were not reduced. At week 6, trained mice showed a paradoxical decrease in plasma lactate during exercise, which was accompanied by an increase in the liver monocarboxylate transporter 2 protein level (∼30%, P < 0.05). Exercise increased liver peroxisomal proliferator-activated receptor-γ coactivator 1α expression (approximately twofold, P < 0.001), NAD-dependent deacetylase sirtuin-1 protein (∼30%, P < 0.05), p38 protein (∼15%, P < 0.05), cytochrome c oxidase subunit 4 isoform 1 protein (∼50%, P < 0.05) and AMP-activated protein kinase phosphorylation (∼40%, P < 0.05). Despite this, liver mitochondrial DNA copy number (∼30%, P = 0.05), mitochondrial transcription factor A expression (∼15%, P < 0.05), cytochrome c oxidase subunit 2 expression (∼10%, P < 0.05), cAMP-response element binding protein phosphorylation (∼60%, P < 0.05) and brain-derived neurotrophic factor expression (∼40%, P < 0.05) were all reduced, while cytochrome oxidase and citrate synthase activities were unchanged. The only altered brain parameter observed was a reduction in tumour necrosis factor α expression (∼35%, P < 0.05); tumour necrosis factor α expression was unchanged in liver. Our data suggest that lactate produced by exercising muscle modifies the liver bioenergetic infrastructure, and enhanced liver uptake may in turn limit the ability of exercise-generated lactate to modify brain bioenergetics. Also, it appears that, at least in the liver, a dissociated mitochondrial biogenesis, in which some components are strategically enhanced while others are minimized, can occur.
authors.affiliation: Department of Physical Therapy and Rehabilitation Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Lezi
authors.initials: L
authors.lastname: E
authors.forename: Jianghua
authors.initials: J
authors.lastname: Lu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Burns
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D050882:CREB-Binding Protein / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology*; D027501:Monocarboxylic Acid Transporters / Q000097:blood; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D056564:Sirtuin 1 / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D027501:Monocarboxylic Acid Transporters; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C490426:Slc16a7 protein, mouse; C081930:Tfam protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1