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- Title
Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity.
- Authors
Deepa, Sathyaseelan S.; Pulliam, Daniel; Hill, Shauna; Yun Shi; Walsh, Michael E.; Salmon, Adam; Sloane, Lauren; Ning Zhang; Zeviani, Massimo; Viscomi, Carlo; Musi, Nicolas; Van Remmen, Holly
- Abstract
Mice lacking Surf1, a complex IV assembly protein, have ~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 (~2-fold) and glucose transporter type 4 (GLUT4; ~1.3-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.
- Subjects
INSULIN resistance; MITOCHONDRIAL DNA; ADIPOSE tissues; PEROXISOME proliferator-activated receptors; GLUCOSE in the body; MITOCHONDRIA formation
- Publication
FASEB Journal, 2013, Vol 27, Issue 4, p1371
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.12-221879