Increased glycolysis is an early consequence of palmitate lipotoxicity mediated by redox signaling

Autor(es)

Kakimoto, Pamela A. ^[1] ; Serna, Julian David C. ^[1] ; Ramos, Vitor de Miranda ^[1] ; Zorzano, Antonio ^[2] ; Kowaltowski, Alicia J. ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Barcelona, CIBER Diabet & Enfermedades Metab Asociadas CIBER, Inst Res Biomed IRB Barcelona, Fac Biol, Inst Salud Carlos III, Dept Bioquim & Biomed Mol, Barcelona - Spain

• Tipo de documento: Artigo Científico
• Fonte: REDOX BIOLOGY; v. 45, SEP 2021.
• Citações Web of Science: 0

Resumo

Exposure to toxic levels of fatty acids (lipotoxicity) leads to cell damage and death and is involved in the pathogenesis of the metabolic syndrome. Since the metabolic consequences of lipotoxicity are still poorly understood, we studied the bioenergetic effects of the saturated fatty acid palmitate, quantifying changes in mitochondrial morphology, real-time oxygen consumption, ATP production sources, and extracellular acidification in hepatoma cells. Surprisingly, glycolysis was enhanced by the presence of palmitate as soon as 1 h after stimulus, while oxygen consumption and oxidative phosphorylation were unchanged, despite overt mitochondrial fragmentation. Palmitate only induced mitochondrial fragmentation if glucose and glutamine were available, while glycolytic enhancement did not require glutamine, showing it is independent of mitochondrial morphological changes. Redox state was altered by palmitate, as indicated by NAD(P)H quantification. Furthermore, the mitochondrial antioxidant mitoquinone, or a selective inhibitor of complex I electron leakage (S1QEL) further enhanced palmitate-induced glycolysis. Our results demonstrate that palmitate overload and lipotoxicity involves an unexpected and early increase in glycolytic flux, while, surprisingly, no changes in oxidative phosphorylation are observed. Interestingly, enhanced glycolysis involves signaling by mitochondrially-generated oxidants, uncovering a novel regulatory mechanism for this pathway. (AU)

• Processo FAPESP: 19/18402-4 - Efeitos da regulação do transporte de cálcio mitocondrial sobre o processo autofágico em hepatócitos
• Beneficiário: Vitor de Miranda Ramos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• 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
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 19/05226-3 - Efeitos de restrição calórica em transporte de Ca2+ mitocondrial em músculo esquelético e cardíaco
• Beneficiário: Julian David Cualcialpud Serna
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto