Research Article Details
| Article ID: | A20613 |
| PMID: | 25850622 |
| Source: | Curr Drug Targets |
| Title: | Identification of Lipid Species Linked to the Progression of Non-Alcoholic Fatty Liver Disease. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is histologically characterized by the aberrant accumulation of lipid droplets in the liver, which is positively correlated with insulin resistance. Within the spectrum of this disease, patients can develop hepatitis and cirrhosis; i.e., non-alcoholic steatohepatitis (NASH). The mechanisms responsible for the progression of NAFLD are not fully understood. Triacylglycerol (TAG), which is mainly found in lipid droplets, is currently considered to act as a buffer against the accumulation of non-TAG toxic lipid species. In line with this, recent studies have revealed that insulin resistance is driven by the accumulation of phosphatidic acid and diacylglycerol in hepatocytes and that cholesterol-overloaded stellate cells are associated with fibrosis in the liver. Therefore, it is important to identify the toxic lipid species that contribute to NAFLD progression in order to clarify the pathogenesis of NASH and find novel targets for its treatment. In this review, we divided lipids into five classes; i.e., into fatty acyls, glycerophospholipids, glycerolipids, sphingolipids, and sterol lipids, and described their molecular structures, distributions, and metabolism under physiological conditions, as well as the contributions they make to the progression of NAFLD. |
| DOI: | 10.2174/1389450116666150408103318 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |