The Role of PPARs in Obesity and other Insulin Resistance Associated Disorders

Author(s): R. Chakrabarti, R. Rajagopalan.

Journal Name: Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents

Volume 4 , Issue 2 , 2004

Abstract:

Overweight and obesity are associated with increased risk of a number of clinically important chronic conditions such as, Type 2 diabetes and several risk factors for coronary heart disease (CHD): atherosclerosis, hypertension, hyperlipidemia, arteriosclerosis. Obesity results from an imbalance between energy intake and expenditure. Generally, anti-obesity pharmacotherapy targets both reduction of energy intake and increase of energy expenditure. Due to several associated abnormalities, it is now considered that an anti-obesity agent which not only reduce weight, but also improve metabolic and cardiovascular functions will have better therapeutic potential. Peroxisome proliferators-activated receptors (PPARs), are lipid activated transcription factors that control carbohydrate and lipid homeostasis. The PPAR subfamily of nuclear receptors comprises three isoforms - PPARα, PPARγ and PPARδ. PPARα is predomionantly involved in fatty acid catabolism, whereas PPARγ promotes lipid storage and triggers cellular differentiation and insulin sensitization. Dual activation of PPARα and γ controls glucose homeostasis, insulin sensitization and lipid metabolism, In addition, PPARα and g activation is also known to exert anti-inflammatory action, exert direct actions for modulating the vascular endothelial functions and thereby showing anti-hypertensive activity. Here we have reviewed the diverse pieces of evidence linking obesity with PPARs and how selective manipulation of PPAR isoforms by agonists or antagonists can potentially lead to the discovery of new drugs to treat weight gain and the related complications.

Keywords: PPARs in Obesity, anti-hypertensive, glucose homeostasis

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Article Details

VOLUME: 4
ISSUE: 2
Year: 2004
Page: [67 - 73]
Pages: 7
DOI: 10.2174/1568013043357833
Price: $58