Fat Controller

Sci. Signal.  17 Jun 2008:
Vol. 1, Issue 24, pp. ec228
DOI: 10.1126/scisignal.124ec228

The synthesis of lipids in the liver depends on transcriptional pathways under the influence of carbohydrate intake. Lee et al. (see also commentary by Horton) provide evidence for a rather unexpected addition to the list of transcription factors involved in lipid metabolism, XBP1. XBP1 is already known to regulate the unfolded protein response (UPR) in the endoplasmic reticulum, influencing the secretory capacity of a variety of cell types. Mice lacking Xbp1 expression in the liver after birth showed reduced levels of cholesterol and triglycerides as a result of attenuated lipid synthesis in the liver. In wild-type mice, the abundance of XBP1 was increased by feeding of carbohydrates and corresponded with the expression of several other genes associated with fatty acid synthesis. It remains unclear exactly how XBP1 helps regulate the complex lipogenic transcriptional network in response to carbohydrate intake.

A.-H. Lee, E. F. Scapa, D. E. Cohen, L. H. Glimcher, Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320, 1492-1496 (2008). [Abstract] [Full Text]

J. D. Horton, Unfolding lipid metabolism. Science 320, 1433-1434 (2008). [Summary] [Full Text]