Research Article Details
| Article ID: | A22869 |
| PMID: | 24265237 |
| Source: | Compr Physiol |
| Title: | Steatosis in the liver. |
| Abstract: | Accumulation of triacylglycerols within the cytoplasm of hepatocytes to the degree that lipid droplets are visible microscopically is called liver steatosis. Most commonly, it occurs when there is an imbalance between the delivery or synthesis of fatty acids in the liver and their disposal through oxidative pathways or secretion into the blood as a component of triacylglycerols in very low density lipoprotein. This disorder is called nonalcoholic fatty liver disease (NAFLD) in the absence of alcoholic abuse and viral hepatitis, and it is often associated with insulin resistance, obesity and type 2 diabetes. Also, liver steatosis can be induced by many other causes including excessive alcohol consumption, infection with genotype 3 hepatitis C virus and certain medications. Whereas hepatic triacylglycerol accumulation was once considered the ultimate effector of hepatic lipotoxicity, triacylglycerols per se are quite inert and do not induce insulin resistance or cellular injury. Rather, lipotoxic injury in the liver appears to be mediated by the global ongoing fatty acid enrichment in the liver, paralleling the development of insulin resistance. A considerable number of fatty acid metabolites may be responsible for hepatic lipotoxicity and liver injury. Additional key contributors include hepatic cytosolic lipases and the "lipophagy" of lipid droplets, as sources of hepatic fatty acids. The specific origin of the lipids, mainly triacylglycerols, accumulating in liver has been unraveled by recent kinetic studies, and identifying the origin of the accumulated triacylglycerols in the liver of patients with NAFLD may direct the prevention and treatment of this condition. |
| DOI: | 10.1002/cphy.c130001 |
| 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 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |