Research Article Details
| Article ID: | A04870 |
| PMID: | 33474802 |
| Source: | Pharmacol Res Perspect |
| Title: | Dexmedetomidine ameliorates high-fat diet-induced nonalcoholic fatty liver disease by targeting SCD1 in obesity mice. |
| Abstract: | Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no therapeutic drugs approved for this pathology. Insulin resistance (IR) is implicated both in pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in disease progression from steatosis to nonalcoholic steatohepatitis. In this study, we have characterized effects of an α2 -adrenoceptor agonist, dexmedetomidine (DEX), which can alleviate IR in hepatocytes in high-fat diet (HFD)-induced NAFLD mice. The NAFLD mice received a daily intraperitoneal administration of DEX (100 μg·kg-1 ) after 16 days exhibited lower body weight, fewer and smaller fat droplets in the liver, markedly reduced the plasma triglyceride levels, accompanied by improvement of liver damage. This inhibition of lipid accumulation activity in obese mice was associated with a robust reduction in the mRNA and protein expression of the lipogenic enzyme stearyl-coenzyme A desaturase 1 (SCD1), which was probably mediated by the inhibition of C/EBP β, PPAR γ and C/EBP α through suppressing α2A -adrenoceptor (α2A -AR) via negative feedback. Additionally, DEX can also improve IR and inflammation by inhibiting the mitogen-activated protein kinases (MAPK) and nuclear factor kappa beta (NFκB) signaling pathway in vivo. Our findings implicate that DEX may act as a potential anti-steatotic drug which ameliorates obesity-associated fatty liver and improves IR and inflammation, probably by suppressing the expression of SCD1 and the inhibition of MAPK/NFκB pathway and suggest the potential adjuvant use for the treatment of NAFLD. |
| DOI: | 10.1002/prp2.700 |
| 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 |
| 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 | |
|---|---|---|---|---|---|
| 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |