Preprint Review Version 1 This version is not peer-reviewed

Liver–Intestine CREBH Regulates Systemic Glucose and Lipid Metabolism

Version 1 : Received: 28 March 2018 / Approved: 28 March 2018 / Online: 28 March 2018 (08:06:15 CEST)

A peer-reviewed article of this Preprint also exists.

Nakagawa, Y.; Shimano, H. CREBH Regulates Systemic Glucose and Lipid Metabolism. Int. J. Mol. Sci. 2018, 19, 1396. Nakagawa, Y.; Shimano, H. CREBH Regulates Systemic Glucose and Lipid Metabolism. Int. J. Mol. Sci. 2018, 19, 1396.

Journal reference: Int. J. Mol. Sci. 2018, 19, 1396
DOI: 10.3390/ijms19051396

Abstract

The cyclic AMP-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 upregulating LPL activity. A deficiency of CREBH in mice leads to severe hypertriglyceridemia. CREBH, in synergy with PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis. CREBH binds to and functions as a co-activator for both PPARα and LXRα in regulating gene expression of lipid metabolism. Furthermore, intestinal CREBH in overexpression reduces cholesterol absorption and suppresses high-cholesterol diet-induced fatty liver. Conversely, a deficiency of CrebH in mice fed on various high-fat diets leads to severe fatty liver. Thus, CREBH could be a therapeutic target in the treatment of metabolic diseases.

Subject Areas

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

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