TY - JOUR
T1 - Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity
AU - Deepa, Sathyaseelan S.
AU - Pulliam, Daniel
AU - Hill, Shauna
AU - Shi, Yun
AU - Walsh, Michael E.
AU - Salmon, Adam
AU - Sloane, Lauren
AU - Zhang, Ning
AU - Zeviani, Massimo
AU - Viscomi, Carlo
AU - Musi, Nicolas
AU - Van Remmen, Holly
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Fatty acid oxidation
KW - Longevity
KW - PGC-1α
KW - Surf1
UR - http://www.scopus.com/inward/record.url?scp=84875728292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875728292&partnerID=8YFLogxK
U2 - 10.1096/fj.12-221879
DO - 10.1096/fj.12-221879
M3 - Article
C2 - 23241310
AN - SCOPUS:84875728292
SN - 0892-6638
VL - 27
SP - 1371
EP - 1380
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -