Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation.
J Biol Chem
; 296: 100622, 2021.
Article
en En
| MEDLINE
| ID: mdl-33811861
ABSTRACT
Fasting induces lipid accumulation in the liver, while the mechanisms by which fasting dysregulates liver fatty acid oxidation are not clear. Fatty acid ω-oxidation is induced in the fasting state, and administration of dicarboxylic acids to fasting animals decreases plasma ketone bodies. We hypothesized that endogenous dicarboxylic acids might play a role in controlling mitochondrial ß-oxidation in fasting animals. A peroxisome proliferator-activated receptor-alpha agonist and an inhibitor for peroxisomal ß-oxidation were administered to the fasting rats to investigate the role of dicarboxylic acids in liver fatty acid oxidation and lipid homeostasis. We observed that excessive ß-oxidation of endogenous dicarboxylic acids by peroxisomes generated considerable levels of succinate in the liver. Excessive succinate oxidation subsequently increased the mitochondrial NADH/NAD+ ratio and led to an accumulation of 3-OH-CoA and 2-enoyl-CoA intermediates in the liver. This further induced feedback suppression of mitochondrial ß-oxidation and promoted hepatic lipid deposition and steatosis. Specific inhibition of peroxisomal ß-oxidation attenuated fasting-induced lipid deposition in the liver by reducing succinate production and enhancing mitochondrial fatty acid oxidation. We conclude that suppression of mitochondrial ß-oxidation by oxidation of dicarboxylic acids serves as a mechanism for fasting-induced hepatic lipid accumulation and identifies cross talk between peroxisomal and mitochondrial fatty acid oxidation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ayuno
/
Peroxisomas
/
Ácidos Dicarboxílicos
/
Metabolismo de los Lípidos
/
Cuerpos Cetónicos
/
Hígado
/
Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2021
Tipo del documento:
Article