Regulation of hepatic lipogenesis by the transcription factor XBP1

AH Lee, EF Scapa, DE Cohen, LH Glimcher - Science, 2008 - science.org
AH Lee, EF Scapa, DE Cohen, LH Glimcher
Science, 2008science.org
Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical
enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a
key regulator of the unfolded protein response, is required for the unrelated function of
normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after
feeding carbohydrates and corresponded with the induction of critical genes involved in fatty
acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked …
Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.
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