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

Sathyaseelan S. Deepa, Daniel Pulliam, Shauna Hill, Yun Shi, Michael E. Walsh, Adam Salmon, Lauren Sloane, Ning Zhang, Massimo Zeviani, Carlo Viscomi, Nicolas Musi, Holly Van Remmen

Research output: Contribution to journalArticle

24 Scopus citations

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 insulinstimulated 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 β-coactivator 1 (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.-Deepa, S. S., Pulliam, D., Hill, S., Shi, Y., Walsh, M. E., Salmon, A., Sloane, L., Zhang, N., Zeviani, M., Viscomi, C., Musi, N., Van Remmen, H. Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity. FASEB J. 27, 1371-1380 (2013). www.fasebj.org.

Original languageEnglish (US)
Pages (from-to)1371-1380
Number of pages10
JournalFASEB Journal
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2013

    Fingerprint

Keywords

  • Fatty acid oxidation
  • Longevity
  • PGC-1α
  • Surf1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Deepa, S. S., Pulliam, D., Hill, S., Shi, Y., Walsh, M. E., Salmon, A., Sloane, L., Zhang, N., Zeviani, M., Viscomi, C., Musi, N., & Van Remmen, H. (2013). Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity. FASEB Journal, 27(4), 1371-1380. https://doi.org/10.1096/fj.12-221879