Research Article Details
| Article ID: | A05185 |
| PMID: | 33343508 |
| Source: | Front Endocrinol (Lausanne) |
| Title: | ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue. |
| Abstract: | Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines. |
| DOI: | 10.3389/fendo.2020.587189 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| 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 |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T22 | Stearoyl-CoA desaturase | SCD | inhibitor | Enzyme | O00767 | SCD_HUMAN | Details |
| T28 | Fibroblast growth factor 21 | FGF21 | analogue | Secreted | Q9NSA1 | FGF21_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |