Research Article Details
| Article ID: | A46333 |
| PMID: | 19474719 |
| Source: | Curr Opin Clin Nutr Metab Care |
| Title: | Metabolic benefits from Sirt1 and Sirt1 activators. |
| Abstract: | PURPOSE OF REVIEW: To evaluate the role of mammalian Sirt1 and Sirt1 activators in the protection from metabolic disorders such as diet-induced obesity, diabetes type 2, or nonalcoholic fatty liver disease. RECENT FINDINGS: Sirtuins are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that are activated by NAD+ and inhibited by NAD in its reduced form (NADH). Sirtuins act as cellular energy sensors that deacetylate numerous proteins involved in energy and glucose homeostasis, which in turn induce a wide range of physiological changes that counteract detrimental effects of metabolic stressors. SUMMARY: Sirt1 targets numerous proteins, including peroxisome proliferator-activated receptor (PPAR)-gamma, PPAR-gamma coactivator (PGC)-1alpha, uncoupling protein 2 (UCP2), and nuclear factor-kappa B, which play key roles in various metabolic disorders. This review summarizes these key targets of Sirt1 and the physiological relevance of those interactions. Also, new results on Sirt1-knockout and overexpressor mouse models are presented to substantiate metabolic benefits from Sirt1 activation. Finally, this review gives an overview on recent efforts to activate Sirt1 pharmacologically by using resveratrol or small-molecule Sirt1 activators with improved biopotency. |
| DOI: | 10.1097/MCO.0b013e32832cdaae |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs |
|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D240 | Nicotinamide | Chemical drug | DB02701 | PARP inhibitor | Metabolic disorder drug | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D301 | Resveratrol | Chemical drug | DB02709 | ALOX15; ALOX5; AHR; NR1I2; NR1I3 | Anticancer agent | Under clinical trials | Details |