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Inhibition of Crif1 protects fatty acid-induced POMC neuron-like cell-line damage by increasing CPT-1 function.
Regina-Ferreira, Lara; Valdivieso-Rivera, Fernando; Angelim, Monara K S C; Menezes Dos Reis, Larissa; Furino, Vanessa O; Morari, Joseane; Maia de Sousa, Lizandra; Consonni, Sílvio Roberto; Sponton, Carlos H; Moraes-Vieira, Pedro M; Velloso, Lício A.
Afiliación
  • Regina-Ferreira L; Obesity and Comorbidities Research Center, São Paulo, Brazil.
  • Valdivieso-Rivera F; Obesity and Comorbidities Research Center, São Paulo, Brazil.
  • Angelim MKSC; Department of Structural and Functional Biology, Institute of Biology (IB), University of Campinas, São Paulo, Brazil.
  • Menezes Dos Reis L; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, São Paulo, Brazil.
  • Furino VO; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, São Paulo, Brazil.
  • Morari J; Obesity and Comorbidities Research Center, São Paulo, Brazil.
  • Maia de Sousa L; Obesity and Comorbidities Research Center, São Paulo, Brazil.
  • Consonni SR; Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology, Institute of Biology (IB), University of Campinas, São Paulo, Brazil.
  • Sponton CH; Laboratory of Cytochemistry and Immunocytochemistry, Department of Biochemistry and Tissue Biology, Institute of Biology (IB), University of Campinas, São Paulo, Brazil.
  • Moraes-Vieira PM; Obesity and Comorbidities Research Center, São Paulo, Brazil.
  • Velloso LA; Department of Structural and Functional Biology, Institute of Biology (IB), University of Campinas, São Paulo, Brazil.
Am J Physiol Endocrinol Metab ; 326(5): E681-E695, 2024 May 01.
Article en En | MEDLINE | ID: mdl-38597829
ABSTRACT
Hypothalamic proopiomelanocortin (POMC) neurons are sensors of signals that reflect the energy stored in the body. Inducing mild stress in proopiomelanocortin neurons protects them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift toward greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.NEW & NOTEWORTHY Saturated fats can damage hypothalamic neurons resulting in positive energy balance, and this is mitigated by mild cellular stress; however, the mechanisms behind this protective effect are unknown. Using a proopiomelanocortin cell line, we show that under exposure to a high concentration of palmitate, the partial inhibition of the mitochondrial protein Crif1 results in protection due to a metabolic shift warranted by the increased expression and activity of the mitochondrial fatty acid transporter CPT-1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carnitina O-Palmitoiltransferasa / Proteínas de Ciclo Celular / Ácidos Grasos / Mitocondrias Límite: Animals Idioma: En Revista: Am J Physiol Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carnitina O-Palmitoiltransferasa / Proteínas de Ciclo Celular / Ácidos Grasos / Mitocondrias Límite: Animals Idioma: En Revista: Am J Physiol Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos