Increased skeletal muscle IRS1 and Akt phosphorylation in HFD-fed SOCS3 MKO mice. A: Principal component analysis of gene expression levels in tibialis anterior muscle from WT and SOCS3 MKO mice fed a chow diet or HFD. A separation between samples can be seen in this visualization (principal component 1 and 2) based on diet (chow = circles, HFD = squares), but samples are not separated based on genotype (WT = white, MKO = black). B: Skeletal muscle protein expression of the IR, IRS1, P85-subunit of PI3 kinase, and Akt from HFD-fed male WT and SOCS3 MKO mice injected with saline. IR Y1150 phosphorylation (C), IRS1-associated P85-subunit of PI3 kinase (D), and Akt T308 and S473 phosphorylation (E) in HFD-fed male WT and SOCS3 MKO mice injected with either saline or insulin are shown. Data are mean ± SE, n = 6–8. *P ≤ 0.05 relative to WT.