Figure 3.

Muscle-specific overexpression of PGC-1α does not defend against glucose intolerance or enhance glucose control in response to exercise and caloric restriction. Mice were fed an HFD for 26 weeks, and measures of insulin action were made at the designated time points. Intraperitoneal glucose tolerance tests (1.5 mg/kg lean body wt) were performed on age-matched cohorts of NT and MCK-PGC1α mice that remained sedentary for the duration of the HFD (A) or were given access to running wheels (HFD+Ex) (B) during weeks 11–20, followed by an additional 10 weeks of exercise combined with 25% caloric restriction (Ex/CR). Blood and tissues were harvested at 30 weeks and used for analysis of fasting insulin levels (C) and glycogen content (D) in gastrocnemius muscles. Insulin-stimulated glycogen synthesis, expressed as fold change relative to basal rates assessed in the contralateral muscles, was measured in isolated soleus (E) and isolated EDL (F). Data were analyzed by two-way ANOVA. A main effect of Ex/CR on insulin, glycogen, and insulin-stimulated glycogen synthesis in the soleus was detected, but symbols were excluded for simplicity. Data represent means ± SEM for 6–8 mice per group. *P < 0.05 between genotypes. #P < 0.05 within a genotype between treatment conditions (sedentary versus Ex/CR). Sed, sedentary; wk, week.