Pioglitazone administration downregulates hepatic mitochondrial TCA cycle activity in mice with NASH. (A) endogenous glucose production, (B) TCA cycle flux, (C) anaplerosis, and (D) pyruvate cycling, determined using 13C-NMR-based isotopomer analysis. TCA cycle flux, anaplerosis, and pyruvate cycling were all downregulated in mice fed a TFD diet supplemented with pioglitazone. E: the robust relationship between hepatic mitochondrial TCA cycle flux and mitochondrial anaplerosis also suggests that pioglitazone could be improving gluconeogenesis by modulating hepatic TCA cycle function. Values are means ± SE (n = 7–8 per group).