Fig. 8.

CR-mediated biotransformation enzyme and transporter expression differs in liver differs for lean and obese mice. The observed effects of caloric restriction (CR) on liver gene expression differed between lean and obese (OB) mice. The figure depicts potential regulation based on nuclear receptor binding and mRNA expression data from the in vivo study. CR is described to activate the AMPK pathway and induce Sirtuin 1 (Sirt1) activation. CR induced Pgc-1α mRNA expression in livers of lean mice, consistent with previous reports, but did not do so in OB mice. Based on previous reports, Pgc-1 and Sirt1 are known to regulate some NRs at the level of mRNA expression and binding to responsive elements. In general, receptor binding and downstream gene expression differed in the lean and OB mice after CR, suggesting that perhaps Sirt1, leptin, and perhaps Pgc-1α, are upstream modulators of biotransformation and excretion processes.