Fig. 7.
Cholesterol and bile acid biosynthesis during relapse. RNA-sequencing data from relapsing rats were mined to determine differential expression of genes that encode proteins in the mevalonate or bile acid biosynthesis pathway. Upper mevalonate pathway regulation was assessed by investigating acetyl-Coenzyme A acetyltransferase 2 (Acat2; A), hydroxymethylglutaryl-CoA synthase 1 (Hmgcs1; B) and hydroxymethylglutaryl-CoA reductase (Hmgcr; C) mRNA expression. Plasma cholesterol levels adapted from the initial report of the dual-tracer study, originally published in Am J Physiol Regul Integr Comp Physiol 301: R656–R667, 2011 (43), are shown (D). Bile acid biosynthesis was assessed by investigating cholesterol 7 α-hydroxylase (Cyp7a1; E) and sterol 27-hydroxylase (Cyp27a1; F) mRNA expression. Data were analyzed by ANOVA, with planned comparisons (n = 5 per group for gene expression data, n = 7–12 for plasma cholesterol data; *P < 0.05;***P < 0.001). Simplified diagram of the mevalonate pathway and downstream cholesterol and bile acid biosynthesis is shown (G). EX, exercise; GM, gap-matched; SED, sedentary; WLM, weight loss maintenance.