Research Article Details
| Article ID: | A24455 |
| PMID: | 22876924 |
| Source: | Curr Med Chem |
| Title: | Adiponectin: key player in the adipose tissue-liver crosstalk. |
| Abstract: | The adipose tissue has recently emerged as an important endocrine organ releasing numerous mediators including adipocytokines, classical cytokines and others. Adiponectin, one of the major products of adipocytes, is a prototypic anti-diabetic adipocytokine, the actions of which are mainly exerted by the activation of AMP-activated kinase and peroxisome proliferator-activated receptor alpha. This adipocytokine is one of the most abundant circulating (adipo)cytokines in health. Non-alcoholic fatty liver disease (NAFLD), the major reason for abnormal liver functions in the western world, is commonly associated with obesity, insulin resistance and decreased adiponectin serum levels. Adiponectin has many anti-inflammatory activities and suppresses tumour necrosis factor-alpha (TNFα), a cytokine of key importance in NAFLD. The anti-inflammatory effects of adiponectin are also exerted by induction of the anti-inflammatory cytokines interleukin-10 (IL-10) or IL-1 receptor antagonist and up-regulation of heme-oxygenase-1. Whereas the liver probably is not a relevant source of circulating adiponectin, it is a major target organ for many adiponectin effects. Adiponectin is able to regulate steatosis, insulin resistance, inflammation and fibrosis. NAFLD is also associated with decreased liver expression of the two adiponectin receptors (AdipoR1 and 2) thereby contributing to a state of hepatic adiponectin resistance. In contrast, most other liver diseases especially in advanced disease states exhibit increased adiponectin serum levels with highest levels observed in cirrhosis. Targeting adiponectin could evolve as a major treatment concept especially for fatty liver diseases in the future. |
| DOI: | 10.2174/092986712803833254 |
| 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 |
| 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 |
| 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 |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |