PMID- 30517024 OWN - NLM STAT- MEDLINE DCOM- 20191230 LR - 20200930 IS - 1522-1490 (Electronic) IS - 0363-6119 (Linking) VI - 316 IP - 3 DP - 2019 Mar 1 TI - The highly efficient powerhouse in the Wistar audiogenic rat, an epileptic rat strain. PG - R243-R254 LID - 10.1152/ajpregu.00254.2018 [doi] AB - The Wistar audiogenic rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister x brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing is known about its mitochondrial metabolism. Here, we addressed mitochondrial aspects of oxidative phosphorylation, oxidative stress, biogenesis, and dynamics in liver, skeletal muscle, and heart of male WARs and correlating them with physiological aspects of body metabolism. The results showed higher mitochondrial content, respiration rates in phosphorylation and noncoupled states, and H(2)O(2) production in WARs. Liver presented higher content of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC1alpha) and mammalian target of rapamycin, proteins related to mitochondrial biogenesis. In agreement, isolated liver mitochondria from WARs showed higher respiration rates in phosphorylation state and ADP-to-O ratio, as well as higher content of proteins related to electron transport chain ATP synthase, TCA cycle, and mitochondrial fusion and fission compared with their Wistar counterparts. Mitochondria with higher area and perimeter and more variable shapes were found in liver and soleus from WARs in addition to lower reduced-to-oxidized glutathione ratio. In vivo, WARs demonstrated lower body mass and energy expenditure but higher food and water intake and amino acid oxidation. When exposed to a running test, WARs reached higher speed and resisted for a longer time and distance than their Wistar controls. In conclusion, the WAR strain has mitochondrial changes in liver, skeletal muscle, and heart that improve its mitochondrial capacity of ATP production, making it an excellent rat model to study PGC1alpha overexpression and mitochondrial function in different physiological conditions or facing pathological challenges. FAU - Dechandt, Carlos Roberto Porto AU - Dechandt CRP AD - Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. FAU - Vicentini, Tatiane M AU - Vicentini TM AD - Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. FAU - Lanfredi, Guilherme Pauperio AU - Lanfredi GP AD - Departamento de Bioquimica e Imunologia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. FAU - Silva-Jr, Rui M P AU - Silva-Jr RMP AD - Departamento de Biologia Celular e Molecular, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. FAU - Espreafico, Enilza Maria AU - Espreafico EM AD - Departamento de Biologia Celular e Molecular, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. FAU - de Oliveira, Jose A Cortes AU - de Oliveira JAC AD - Departamento de Fisiologia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. FAU - Faca, Vitor Marcel AU - Faca VM AD - Departamento de Bioquimica e Imunologia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. FAU - Garcia-Cairasco, Norberto AU - Garcia-Cairasco N AD - Departamento de Fisiologia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. FAU - Alberici, Luciane Carla AU - Alberici LC AUID- ORCID: 0000-0002-7464-9385 AD - Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181205 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, rat) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Adenosine Triphosphate/biosynthesis MH - Animals MH - Body Weight MH - Energy Metabolism MH - Epilepsy, Reflex/*metabolism MH - Hydrogen Peroxide/metabolism MH - Liver/metabolism MH - Male MH - Mitochondria, Liver/metabolism MH - Muscle, Skeletal/metabolism MH - Myocardium/metabolism MH - Oxidative Phosphorylation MH - Oxidative Stress MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/biosynthesis/metabolism MH - Rats MH - Rats, Wistar MH - Running OTO - NOTNLM OT - Wistar audiogenic rat strain OT - body metabolism OT - experimental epilepsy model OT - liver OT - mitochondria OT - mitochondrial dynamics OT - reactive oxygen species EDAT- 2018/12/06 06:00 MHDA- 2019/12/31 06:00 CRDT- 2018/12/06 06:00 PHST- 2018/12/06 06:00 [pubmed] PHST- 2019/12/31 06:00 [medline] PHST- 2018/12/06 06:00 [entrez] AID - 10.1152/ajpregu.00254.2018 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2019 Mar 1;316(3):R243-R254. doi: 10.1152/ajpregu.00254.2018. Epub 2018 Dec 5.