The molecular mechanism that CREBH activation by nutrition improves metabolic syndrome

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Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis. Here we demonstrate that a membrane-bound transcription factor, cAMP responsive element binding protein-H (CREBH), is activated during fasting, which mediates a wide spectrum of metabolic responses to starvation. Adenoviral and transgenic overexpression of CREBH reduces plasma lipid and glucose levels and body weight in both normal and diabetic obese mice. CREBH directly transactivates fibroblast growth factor 21 and its plasma level, which is at least partially attributed to these effects of CREBH on the systemic energy homeostasis.