Figure 1

Female 129X1/SvJ Actn3 KO mice show reduced body weight following 92 days of high-fat feeding (a, b). DXA analysis of HFF Actn3 KO mice show reduced lean and fat mass compared to HFF WT mice (c, d). Individual tissue weights for inguinal, renal, and gonadal fat pads as well as the gastrocnemius (GST) muscle show that HFF Actn3 KO mice have reduced fat and muscle mass (e). Male 129X1/SvJ Actn3 KO mice also show reduced weight gain following 71 days on a high-fat diet (f). However, two independent HFF male C57BL/6J Actn3 WT and KO cohorts show significant weight gain compared to CHOW-fed controls (f–i), but no difference between genotype following HFF. For the Female 129X1/SvJ cohort: WT HFF n=22; KO HFF n=18; WT CHOW n=6; KO CHOW n=9. Male 129X1/SvJ mice: WT HFF=7; KO HFF=5; WT CHOW=3; KO CHOW=4. Male C57BL/6J (cohort 1) were fed a HFD for 204 days and consisted of: WT HFF n=6; KO HFF n=6; WT CHOW n=4; KO CHOW n=5; Cohort 2 were fed a HFD for 94 days and consisted of WT HFF n=11; KO HFF n=12; WT CHOW n=10; KO CHOW n=10. All the data are mean values±s.e.m. and statistical analyses were performed using two-way ANOVA in GraphPad prism (version 7, La Jolla, CA, USA). Significance is represented by *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.