Research Article Details
| Article ID: | A45651 |
| PMID: | 23448486 |
| Source: | Curr Pharm Des |
| Title: | Role of adiponectin in the metabolic syndrome: current perspectives on its modulation as a treatment strategy. |
| Abstract: | Adiponectin, a secretory protein specifically expressed by adipose tissue, has been shown to play a critical role in the maintenance of metabolic homeostasis. A deficiency of adiponectin has been linked to a wide variety of metabolic abnormalities, including obesity and associated disorders such as insulin resistance, hyperglycemia, dyslipidemia, hypertension and nonalcoholic fatty liver disease, collectively referred to as the "metabolic syndrome". Conversely, increased expression of adiponectin corrects these abnormalities, as revealed by the positive metabolic effects observed in genetic over expression studies or by administration of recombinant adiponectin. This has led to widespread interest in its role as a therapeutic target for treatment of a range of metabolic disorders such as diabetes mellitus, obesity, inflammatory and cardiovascular diseases. Various therapeutic approaches targeted at increasing adiponectin levels, or its activity, are being explored. These consist of increasing expression of adiponectin or its receptors by inducers, increasing circulating levels of adiponectin by administering recombinant protein, peptide mimetic approaches, or increasing expression/activity of its downstream effectors such as AMPK or PPAR alpha. Many of these approaches have achieved therapeutic benefits in animal models of metabolic diseases. Despite the profusion of research on adiponectin and ways to modulate it, there are limited number of studies focused on smallmolecule based-therapeutic approaches. In this review, we summarize what is currently known with respect to the therapeutic potential of adiponectin and discuss the challenges in designing small molecule-based therapies. |
| DOI: | 10.2174/13816128113199990360 |
| 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 | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| 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 |