Fig. 4.
Hepatic gene expression: during short or long-term feeding of KD, critical metabolic regulators remain elevated (A) and de novo lipogenic/triglyceride synthesis-genes remain depressed (B). With a few exceptions, expression in the liver of genes involved in fatty acid oxidation and ketogenesis elevate upon KD feeding and remain elevated long-term (C & D). KD feeding and/or aging increases gene expression markers (E) and the serum marker aminotransferase (F) of hepatic inflammation and fibrosis, but the increase is not cumulative. PPARγ, peroxisome proliferator-activated receptor gamma; FGF21, fibroblast growth factor 21; PGC1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; UCP2, uncoupling protein 2, SCD-1, stearoyl-CoA desaturase-1; FAS, fatty acid synthase; DGAT2, diglyceride acyltransferase; SREBP1c, sterol regulatory element-binding transcription factor 1c; ACADM, acyl-Coenzyme A dehydrogenase [medium chain]; ACADL, acyl-Coenzyme A dehydrogenase [long chain]; ACADVL, acyl-Coenzyme A dehydrogenase [very long chain]; Hmgcs2, 3-hydroxy-3-methylgutaryl-CoA synthase 2 (mitochondrial); BDH1, 3-hydroxybutyrate dehydrogenase (type 1); HADH, hydroxyacyl-CoA dehydrogenase; MCP1, monocyte chemotactic protein-1; Cd68, cluster of differentiation 68; Mmp2, matrix metalloproteinase-2; TIMP1, tissue inhibitor of metalloproteinase 1. Graphs are shown means ± SEM. Two-way ANOVA utilized on all data sets, effects of duration and diet queried, post-hoc comparisons determined by Sidak’s post-hoc test for individual time point analysis, significance (P < 0.05) is designated by letters: asignificantly different from STCH; bsignificantly different from LTCH; csignificantly different from STKD; dsignificant effect of diet; and esignificant effect of age. n = 4–9 per group.