Research Article Details
| Article ID: | A35531 |
| PMID: | 20425484 |
| Source: | Curr Gastroenterol Rep |
| Title: | Nontriglyceride hepatic lipotoxicity: the new paradigm for the pathogenesis of NASH. |
| Abstract: | Lipid droplet accumulation and oxidant stress, once thought to play essential roles in the pathogenesis of nonalcoholic steatohepatitis (NASH), may actually represent parallel epiphenomena. Emerging data now point to nontriglyceride lipotoxicity and complex mechanisms of hepatocyte injury and apoptosis as the major contributors to the disease phenotype currently recognized as NASH. Although specific mediators of hepatic lipotoxicity have not been identified with certainty, abundant evidence from animal studies and recent data in humans indicate that free fatty acids in the liver can serve as substrates for formation of nontriglyceride lipotoxic metabolites that cause liver injury. The accumulation of triglyceride in droplets may actually be protective, and thus therapeutic efforts directed at fat accumulation as a sole endpoint may be misguided. This review examines the new evidence supporting the role of nontriglyceride fatty acid metabolites in causing NASH and how adipose and muscle insulin resistance contribute to hepatic lipotoxicity. |
| DOI: | 10.1007/s11894-009-0083-6 |
| 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 |
| 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 |