TY - JOUR
T1 - CREBH
T2 - A Complex Array of Regulatory Mechanisms in Nutritional Signaling, Metabolic Inflammation, and Metabolic Disease
AU - Wade, Henry
AU - Pan, Kaichao
AU - Su, Qiaozhu
N1 - Funding Information:
This work was supported by a grant from British Heart Foundation (UK) (PG/19/86134788) and a grant from Northern Ireland Chest Heart and Stroke (2019_08) to Q.S. H.W. is a recipient of PhD research scholarship from the Department for the Economy in Northern Ireland, UK.
Publisher Copyright:
© 2020 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH
PY - 2021/1
Y1 - 2021/1
N2 - The endoplasmic reticulum (ER)-resident basic leucine zipper (bZIP) transcription factor c-AMP responsive element binding protein H (CREBH/CREB3L3) is exclusively expressed in the liver and intestine. Physiologically, CREBH is intrinsically linked to nutritional homeostasis via its regulation on fatty acid β-oxidation, lipid droplet process, very low-density lipoprotein metabolism, gluconeogenesis, and iron metabolism. Pathologically, CREBH enhances hepatic acute-phase response gene expression (e.g., C-reactive protein and serum amyloid P-component) and mediates nutrient-surplus induced metabolic inflammation. Hyperactivation of CREBH in metabolic inflammation further contributes to the development of hyperlipidemia, lipotoxicity, non-alcoholic fatty liver disease, and potentially non-alcoholic steatohepatitis. This review highlights recent findings that delineate the interactions between CREBH and peroxisome proliferator activated receptor α (PPARα), fibroblast growth factor 21 (FGF21), fat-specific protein 27 (FSP27), and lipoprotein metabolism with a focus on the molecular and biochemical mechanisms that underlie the development of metabolic inflammation, non-alcoholic fatty liver disease and inflammatory associated bone disease.
AB - The endoplasmic reticulum (ER)-resident basic leucine zipper (bZIP) transcription factor c-AMP responsive element binding protein H (CREBH/CREB3L3) is exclusively expressed in the liver and intestine. Physiologically, CREBH is intrinsically linked to nutritional homeostasis via its regulation on fatty acid β-oxidation, lipid droplet process, very low-density lipoprotein metabolism, gluconeogenesis, and iron metabolism. Pathologically, CREBH enhances hepatic acute-phase response gene expression (e.g., C-reactive protein and serum amyloid P-component) and mediates nutrient-surplus induced metabolic inflammation. Hyperactivation of CREBH in metabolic inflammation further contributes to the development of hyperlipidemia, lipotoxicity, non-alcoholic fatty liver disease, and potentially non-alcoholic steatohepatitis. This review highlights recent findings that delineate the interactions between CREBH and peroxisome proliferator activated receptor α (PPARα), fibroblast growth factor 21 (FGF21), fat-specific protein 27 (FSP27), and lipoprotein metabolism with a focus on the molecular and biochemical mechanisms that underlie the development of metabolic inflammation, non-alcoholic fatty liver disease and inflammatory associated bone disease.
KW - CREBH
KW - FGF21
KW - FSP27
KW - VLDL and metabolic inflammation
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U2 - 10.1002/mnfr.202000771
DO - 10.1002/mnfr.202000771
M3 - Review article
C2 - 32997872
AN - SCOPUS:85092772292
SN - 1613-4125
VL - 65
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 1
M1 - 2000771
ER -