The role of CREB-H transcription factor in triglyceride metabolism.

PURPOSE OF REVIEW:Cyclic-AMP-responsive-element-binding protein H (CREB-H) is a transcription factor that is highly and selectively expressed in liver and small intestine. Here I summarize recent findings on the role of CREB-H in lipid metabolism. RECENT FINDINGS:Recent studies have demonstrated that hepatic CREB-H is transcriptionally activated by fasting, and induces lipid metabolism genes, such as Apoa4, Apoa5, and Apoc2 apolipoproteins which exhibit stimulatory effects on lipoprotein lipase (LPL). Consistent with the essential role of LPL in triglyceride clearance, CREB-H-deficient mice showed hypertriglyceridemia, associated with defective production of these apolipoproteins and decreased LPL activity. DNA sequencing of the CREB3L3 gene (encoding CREB-H) identified multiple nonsynonymous mutations in CREB3L3 in individuals with extreme hypertriglyceridemia. SUMMARY:Recent studies uncover a novel function of CREB-H in the regulation of triglyceride metabolism in rodents and humans. In liver and small intestine, CREB-H induces LPL coactivators, Apoa4, Apoa5, and Apoc2 that facilitate triglyceride clearance from plasma.

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