Abstract
The prevalence of obesity in the USA and worldwide has reached epidemic proportions during the last two decades. Drugs currently available for the treatment of obesity provide no more than 5% placebo-adjusted weight loss and are associated with undesirable side effects. Peroxisome proliferator-activated receptor (PPAR) modulators offer potential benefits for the treatment of obesity and its associated complications but their development has been complicated by biological, technical, and regulatory challenges. Despite significant challenges, PPAR modulators are attractive targets for the treatment of obesity and could offer a viable alternative to the millions of patients who fail to lose weight following rigorous dieting and exercise protocols. In addition, PPAR modulators have the potential-added benefit of ameliorating the associated comorbidities.
Highlights
During the last two decades, the incidence of obesity has tripled in developing countries, with more than 1.1 billion adults overweight worldwide and 312 million of them obese [1]
The surgical removal of as little as 0.6 kg (0.8% total fat) of Visceral adipose tissue (VAT) significantly ameliorated insulin sensitivity in obese patients [9], whereas removal of large amounts of subcutaneous adipose tissue did not [10]. These findings suggested that adipose tissue can no longer be considered an inert tissue strictly involved in lipid storage but is rather an endocrine organ capable of regulating several aspects of metabolism
Peroxisome proliferator-activated receptor (PPAR) belong to the nuclear receptor family of transcription factors and are master regulators of genes involved in glucose and lipid metabolism
Summary
During the last two decades, the incidence of obesity has tripled in developing countries, with more than 1.1 billion adults overweight worldwide and 312 million of them obese [1]. The surgical removal of as little as 0.6 kg (0.8% total fat) of VAT significantly ameliorated insulin sensitivity in obese patients [9], whereas removal of large amounts of subcutaneous adipose tissue did not [10] These findings suggested that adipose tissue can no longer be considered an inert tissue strictly involved in lipid storage but is rather an endocrine organ capable of regulating several aspects of metabolism. The antidiabetic GLP-1 agonist exenatide (Byetta) was shown to significantly reduce mean body weight (−4.7%) from baseline after 2 years of treatment [13] This drug offers benefits over existing therapies as it combines weight loss and improvements in glycosylated hemoglobin (HbA1c), liver function, and blood pressure [13]. PPARδ agonism either alone or in combination with agonism of PPARα and/or PPARγ could induce body weight loss but could potentially improve other metabolic parameters including insulin sensitivity and lipid profiles, producing benefits associated with the comorbidities of the obese state
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.