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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Kakimoto, Pamela A. [1] ; Serna, Julian David C. [1] ; Ramos, Vitor de Miranda [1] ; Zorzano, Antonio [2] ; Kowaltowski, Alicia J. [1]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: REDOX BIOLOGY; v. 45, SEP 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 19/18402-4 - Effects of mitochondrial calcium transport regulation in autophagic process of hepatocytes
Grantee:Vitor de Miranda Ramos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/25862-0 - Hepatic bioenergetics and redox signaling in obesity murine model: integrative analysis of nutritional, hormonal, and inflammatory stimuli
Grantee:Pâmela Aiako Hypólito Brito Kakimoto
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 19/05226-3 - Effects of caloric restriction on mitochondrial Ca2+ transport in cardiac and skeletal muscles
Grantee:Julian David Cualcialpud Serna
Support type: Scholarships in Brazil - Doctorate (Direct)