Resilient hepatic mitochondria! function and lack of iNOS dependence in diet-induced insulin resistance

Autor(es)

Kakimoto, Pamela A. ^[1] ; Chausse, Bruno ^{[1, 2]} ; Caldeira da Silva, Camille C. ^[1] ; Donato Junior, Jose Prime ^[3] ; Kowaltowski, Alicia J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[2] Heidelberg Univ, Inst Physiol & Pathophysiol, Heidelberg - Germany

^[3] Univ Sao Paulo, Inst Ciencia Biomed, Dept Fisiol & Biofis, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 14, n. 2 FEB 4 2019.
• Citações Web of Science: 0

Resumo

Obesity-derived inflammation and metabolic dysfunction has been related to the activity of the inducible nitric oxide synthase (iNOS). To understand the interrelation between metabolism, obesity and NO., we evaluated the effects of obesity-induced NO. signaling on liver mitochondrial function. We used mouse strains containing mitochondrial nicotinamide transhydrogenase activity, while prior studies involved a spontaneous mutant of this enzyme, and are, therefore, more prone to oxidative imbalance. Wild-type and iNOS knockout mice were fed a high fat diet for 2, 4 or 8 weeks. iNOS knockout did not protect against diet induced metabolic changes. However, the diet decreased fatty-acid oxidation capacity in liver mitochondria at 4 weeks in both wild-type and knockout groups; this was recovered at 8 weeks. Interestingly, other mitochondrial functional parameters were unchanged, despite significant modifications in insulin resistance in wild type and iNOS knockout animals. Overall, we found two surprising features of obesity-induced metabolic dysfunction: (i) iNOS does not have an essential role in obesity-induced insulin resistance under all experimental conditions and (ii) liver mitochondria are resilient to functional changes in obesity-induced metabolic dysfunction. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/07670-7 - Perfis de ativação da microglia e suas respectivas Reprogramações metabólicas
• Beneficiário: Bruno Chausse de Freitas
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/18972-0 - EMU concedido no projeto 17/02983-2: equipamento compacto de ressonância magnética minispec LF50
• Beneficiário: Jose Donato Junior
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 15/25862-0 - Bioenergética e sinalização redox hepática em modelo murino de obesidade: análise integrativa de estímulos nutricionais, hormonais e inflamatórios
• Beneficiário: Pâmela Aiako Hypólito Brito Kakimoto
• Linha de fomento: Bolsas no Brasil - Doutorado Direto