Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity.

TitleImproved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity.
Publication TypeJournal Article
Year of Publication2013
AuthorsDeepa, SS, Pulliam, D, Hill, S, Shi, Y, Walsh, ME, Salmon, A, Sloane, L, Zhang, N, Zeviani, M, Viscomi, C, Musi, N, Van Remmen, H
JournalFASEB J
Date Published2013 Apr
KeywordsAdipose Tissue, White, Animals, Electron Transport Complex IV, Glucose Transporter Type 4, Insulin, Insulin Resistance, Male, Membrane Proteins, Mice, Mitochondria, Mitochondrial Proteins, Muscle, Skeletal, Oxidation-Reduction, PPAR gamma, Receptor, Insulin

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.

Alternate JournalFASEB J.
Citation Key10.1096/fj.12-221879
PubMed ID23241310
Grant ListGPP10005 / / Telethon / Italy
I01 BX000517 / BX / BLRD VA / United States