Research Article Details
| Article ID: | A07515 |
| PMID: | 32461046 |
| Source: | Clin Chim Acta |
| Title: | Emerging role of Insig-1 in lipid metabolism and lipid disorders. |
| Abstract: | Growing evidence has demonstrated that Insig-1 is intricately involved in lipid metabolism regulation and the progression of lipid disorders. Our review summarizes updated information on the role and underlying mechanisms of Insig-1 in lipid metabolism dyshomeostasis and lipid disorders. As a member of the insulin-induced gene family, insulin-induced gene 1 (Insig-1) is a six-span transmembrane protein embedded in the endoplasmic reticulum (ER) membrane. Insig-1 is widely involved in the maintenance of intracellular lipid metabolism homeostasis by controlling the activation of sterol regulatory element-binding proteins (SREBPs) and the degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). Growing experimental and clinical data have identified that Insig-1 reduces lipid accumulation in hepatocytes to relieve the development of nonalcoholic fatty liver disease (NAFLD), downregulates the plasma level of free cholesterol and protects β cells against lipotoxicity to alleviate diabetic dyslipidemia. In addition, Insig-1 suppresses adipogenesis and inhibits the differentiation of preadipocytes to prevent the occurrence of obesity. Insig-1 is a key regulatory factor that maintains intracellular lipid metabolism homeostasis and is a promising therapeutic target for lipid disorders. |
| DOI: | 10.1016/j.cca.2020.05.042 |
| 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 |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | 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 |
| 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 |