Research Article Details
| Article ID: | A06125 |
| PMID: | 32997872 |
| Source: | Mol Nutr Food Res |
| Title: | CREBH: A Complex Array of Regulatory Mechanisms in Nutritional Signaling, Metabolic Inflammation, and Metabolic Disease. |
| Abstract: | 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. |
| DOI: | 10.1002/mnfr.202000771 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I15 | 1290 | Bone disease | A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease | disease of anatomical entity/ musculoskeletal system disease/connective tissue disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |