| First Author | Deepa SS | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 4 | Pages | 1371-80 |
| PubMed ID | 23241310 | Mgi Jnum | J:197658 |
| Mgi Id | MGI:5494229 | Doi | 10.1096/fj.12-221879 |
| Citation | Deepa SS, et al. (2013) Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity. FASEB J 27(4):1371-80 |
| abstractText | Mice lacking Surf1, a complex IV assembly protein, have approximately 50-70% 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 ( approximately 2-fold) and glucose transporter type 4 (GLUT4; approximately 1.3-fold) levels in WAT in the Surf1(-/-) mice. The expression of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1alpha) mRNA and protein was up-regulated by 2.5- and 1.9-fold, respectively, in WAT from Surf1(-/-) mice, and the expression of PGC-1alpha 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. |
