Cellular fatty acid level regulates the effect of tolylfluanid on mitochondrial dysfunction and insulin sensitivity in C2C12 skeletal myotubes.
Biochem Biophys Res Commun
; 505(2): 392-398, 2018 10 28.
Article
en En
| MEDLINE
| ID: mdl-30262144
ABSTRACT
Previous research suggests that the endocrine disrupting chemical tolylfluanid (TF) may promote metabolic dysfunction and insulin resistance in humans. The potential impact of TF on skeletal muscle metabolism has yet to be fully investigated. The purpose of this study was to determine whether TF can promote insulin resistance and metabolic dysfunction in mammalian skeletal muscle cells. C2C12 murine skeletal myotubes were exposed to 1â¯ppmâ¯TF for 24â¯h. To examine the potential effect of cellular fatty acid levels on TF-dependent regulation of mitochondrial metabolism and insulin signaling, we treated skeletal myotubes with 0.25â¯mM or 1.0â¯mM oleic acid (OA) during TF exposure trials. Tolylfluanid (1-10â¯ppm) reduced lipid accumulation by approximately 20% in 0.25 and 1.0â¯mM OA treated cells. The addition of 0.25â¯mM OA completely inhibited the TF-dependent reduction in maximal mitochondrial oxygen consumption rate (OCR) while 1.0â¯mM OA exacerbated the TF-dependent reduction in mitochondrial OCR. Exposing skeletal myotubes to 1â¯ppmâ¯TF promoted an 80% reduction in mitochondrial membrane potential, which was completely inhibited by 0.25â¯mM OA and partially inhibited by1.0â¯mM OA. The addition of 0.25â¯mM OA promoted a TF-dependent increase in insulin-dependent P-Akt (Ser473). In contrast, the addition of 1.0â¯mM OA promoted a significant reduction in insulin-dependent P-Akt (Ser473). Further, the addition of 1â¯ppmâ¯TF significantly reduced insulin-dependent mTORC1 activity regardless of OA concentration. Finally, TF significantly reduced insulin-dependent protein synthesis in the 1â¯mM OA treated cells only. Our results demonstrate that the effect of 1â¯ppmâ¯TF on mitochondrial function and insulin-dependent protein synthesis in skeletal myotubes was largely dependent upon cellular fatty acid levels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Toluidinas
/
Resistencia a la Insulina
/
Fibras Musculares Esqueléticas
/
Enfermedades Mitocondriales
/
Ácidos Grasos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos