Hepatic glucose sensing: does flux matter?

In this issue of the JCI, Denechaud et al. report studies investigating the role of the liver X receptors (LXRs) LXRalpha and LXRbeta in carbohydrate sensing by the liver (see the related article beginning on page 956). The results of this study, which utilized LXRalpha/beta double-KO mice, strongly contradict a recent Nature report that proposed that LXRalpha/beta sense glucose independent of metabolic flux. The reported findings further support a key role for the carbohydrate-responsive element-binding protein (ChREBP) in the regulation of lipogenic genes by glucose and dietary carbohydrates.