Research Article Details
| Article ID: | A26524 |
| PMID: | 20368747 |
| Source: | Clin Lipidol |
| Title: | Mechanisms and clinical implications of hepatocyte lipoapoptosis. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance, elevated serum levels of free fatty acids (FFAs) and fatty infiltration of the liver. Accumulation of triglycerides in the hepatocyte results from the uptake and esterification of circulating FFAs by the liver. Contrary to current theory, hepatic steatosis appears to be a detoxification process, as FFAs are directly cytotoxic for the hepatocyte and inhibition of triglyceride formation enhances FFAs toxicity. Hepatocyte apoptosis is a key feature of NAFLD and correlates with disease severity. Since FFA-induced toxicity, or lipoapoptosis, represents a mechanism for the pathogenesis of NAFLD, this article will highlight the cellular pathways contributing to hepatocyte lipoapoptosis. To date, there is no proven effective therapy for patients with NAFLD and insights into the molecular mediators of lipoapoptosis should help promote effective therapeutic strategies for this disease. |
| DOI: | 10.2217/clp.09.85 |
| 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |