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Int J Mol Sci. 2018 May 8;19(5). pii: E1396. doi: 10.3390/ijms19051396.

CREBH Regulates Systemic Glucose and Lipid Metabolism.

Nakagawa Y1,2, Shimano H3,4,5,6.

Author information

1
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. ynakagawa@md.tsukuba.ac.jp.
2
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. ynakagawa@md.tsukuba.ac.jp.
3
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. hshimano@md.tsukuba.ac.jp.
4
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. hshimano@md.tsukuba.ac.jp.
5
Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan. hshimano@md.tsukuba.ac.jp.
6
Japan Agency for Medical Research and Development⁻Core Research for Evolutional Science and Technology (AMED-CREST), Chiyoda-ku, Tokyo 100-1004, Japan. hshimano@md.tsukuba.ac.jp.

Abstract

The cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL) activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα), has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα) in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.

KEYWORDS:

CREBH; FGF21; LXRα; PPARα; SREBP; lipid metabolism; transcription

PMID:
29738435
PMCID:
PMC5983805
DOI:
10.3390/ijms19051396
[Indexed for MEDLINE]
Free PMC Article

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