Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity.
FASEB J
; 27(4): 1371-80, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23241310
ABSTRACT
Mice lacking Surf1, a complex IV assembly protein, have â¼50-70% reduction in cytochrome c oxidase activity in all tissues yet a paradoxical increase in lifespan. Here we report that Surf1(-/-) mice have lower body (15%) and fat (20%) mass, in association with reduced lipid storage, smaller adipocytes, and elevated indicators of fatty acid oxidation in white adipose tissue (WAT) compared with control mice. The respiratory quotient in the Surf1(-/-) mice was significantly lower than in the control animals (0.83-0.93 vs. 0.90-0.98), consistent with enhanced fat utilization in Surf1(-/-) mice. Elevated fat utilization was associated with increased insulin sensitivity measured as insulin-stimulated glucose uptake, as well as an increase in insulin receptor levels (â¼2-fold) and glucose transporter type 4 (GLUT4; â¼1.3-fold) levels in WAT in the Surf1(-/-) mice. The expression of peroxisome proliferator-activated receptor γ-coactivator 1-α (PGC-1α) mRNA and protein was up-regulated by 2.5- and 1.9-fold, respectively, in WAT from Surf1(-/-) mice, and the expression of PGC-1α target genes and markers of mitochondrial biogenesis was elevated. Together, these findings point to a novel and unexpected link between reduced mitochondrial complex IV activity, enhanced insulin sensitivity, and increased mitochondrial biogenesis that may contribute to the increased longevity in the Surf1(-/-) mice.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Receptor de Insulina
/
Complejo IV de Transporte de Electrones
/
Proteínas Mitocondriales
/
Proteínas de la Membrana
/
Mitocondrias
Tipo de estudio:
Diagnostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos