ADIPOKINE EXPRESSION AND SECRETION: A TARGET FOR PHARMACOLOGIC TREATMENT
Paska A. Permana
Research Service, Carl T. Hayden VA Medical Center, Phoenix, AZ, USA
Obesity and insulin resistance are important risk factors for major diseases such as metabolic syndrome, type 2 diabetes mellitus, and atherosclerotic cardiovascular disease. Chronic subclinical inflammation appears to underlie these disorders. Increasing evidence suggests that dysregulation of metabolically active adipose tissue contributes to systemic inflammation in part by secreting higher concentrations of pro-inflammatory adipokines (a diverse set of bioactive proteins produced by adipose tissue). Some adipokines act as endocrine factors directly enhancing systemic inflammation. Increased secretion of these adipokines results from local adipose tissue inflammation that is mediated by autocrine and paracrine pathways. Adipokine expression and thus secretion are modulated by intercellular cross talk within adipose tissue, including that between adipocytes and macrophages (and possibly mast cells), as well as by oxidative stress and activation of pro-inflammatory pathways such as nuclear factor kappa B and mitogen-activated protein kinase pathways. These regulators of adipokine expression and secretion may serve as therapeutic targets for pharmacologic agents that ameliorate the above adipokine-related diseases. These agents include the widely used angiotensin II type 1 receptor blockers, inhibitors of angiotensin-converting enzyme, metformin, thiazolidinediones, statins, salicylates, as well as others yet to be developed. Biomed Rev 2006; 17: 63-72.
Key words: adipokines, adipose tissue, cardiovascular disease, diabetes, drug
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Received 7 November 2006, received revised 25 November 2006, accepted 26 November 2006. Correspondence and reprint request to Dr Paska A. Permana, Research Service, Carl T. Hayden VA Medical Center, 650 Indian School Rd., Phoenix, AZ 85012-1892, USA. Tel.: 602 277 5551 (ext. 6085), Fax: 602 200 6004
E-mail: Paska.Permana@va.gov
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