Research Article Details
| Article ID: | A03468 |
| PMID: | 33991615 |
| Source: | Cell Signal |
| Title: | Secretory Galectin-3 promotes hepatic steatosis via regulation of the PPARγ/CD36 signaling pathway. |
| Abstract: | Galectin-3 (Gal3) is an essential regulator of a number of metabolic disorders. Previous studies have established that Gal3 is a positive regulator of inflammation, fibrosis, and insulin resistance. However, its function in the early pathogenesis of hepatic lipid accumulation in non-alcoholic fatty liver disease (NAFLD) remains unresolved. Here, we demonstrate the presence of significantly upregulated extracellular concentrations of Gal3 in the fatty livers of high-fat diet (HFD)-induced mice. Systemic inhibition of Gal3 by injection of TD139 reduced the accumulation of lipid in the livers of HFD-fed mice, accompanied by the decreased expression of CD36 and peroxisome proliferator-activated receptor-gamma (PPARγ). Treatment with Gal3 protein elicited the opposite response in palmitic acid (PA)-induced HepG2 hepatocytes. It was additionally discovered that Gal3 positively regulates CD36 transcription by increased activation of PPARγ, thereby increasing fatty acid uptake, resulting in hepatic steatosis. In conclusion, the present study confirmed the roles of Gal3 in hepatic lipid metabolism in both in vitro and in vivo studies and revealed that Gal3 is a secretory protein that promotes hepatic steatosis through the PPARγ-CD36-dependent pathway, suggesting that targeting Gal3 may represent a potential therapeutic approach for the treatment of NAFLD and related metabolic disorders. |
| DOI: | 10.1016/j.cellsig.2021.110043 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |