Research Article Details
| Article ID: | A26450 |
| PMID: | 20460908 |
| Source: | Dig Dis |
| Title: | The role of cytokines in non-alcoholic fatty liver disease. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity and diabetes, and is characterized by insulin resistance (IR). Cytokines and adipocytokines (i.e. mediators mainly derived from adipose tissue) play a major role in the orchestration of inflammatory processes throughout the body. In addition, many of these mediators are able to regulate very diverse functions including inflammatory, immune and metabolic processes such as IR. The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are critically involved in the pathophysiology of various aspects of human NAFLD. The importance of TNF-alpha in human and animal fatty liver diseases, both due to genetic manipulation and overnutrition, has been demonstrated. Furthermore, neutralization of TNF-alpha activity improves IR and fatty liver disease in animals. IL-6 is derived from many cells throughout the body including adipocytes. Serum levels of this cytokine correlate remarkably well with the presence of IR, and adipose tissue-derived IL-6 has been shown to regulate hepatic IR via upregulation of SOCS3. Adiponectin is a potent TNF-alpha-neutralizing and anti-inflammatory adipocytokine, and in vitro and experimental animal studies have proven the importance of this mediator in counteracting inflammation and IR. Anti-inflammatory effects of adiponectin are mediated via suppression of TNF-alpha synthesis as well as induction of anti-inflammatory cytokines such as IL-10 or IL-1 receptor antagonist. Therefore, the balance between pro- and anti-inflammatory acting cytokines/adipocytokines appears to play a key role in hepatic and systemic insulin action, and they are supposed to have important functions in the development of NAFLD. |
| DOI: | 10.1159/000282083 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | 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 |