Peptidomimetic Targeting White Fat Causes Weight Loss and Improved Insulin Resistance

Discussion in 'Men's Health Forum' started by Michael Scally MD, Jan 5, 2012.

  1. #1
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    IMO, the pathway to treat obesity will be along these lines - hormonal. Also, this is a Houston company, FWIW.

    Arrowhead Research Corp. (NasdaqCM: ARWR)
    Arrowhead Research Corporation | ARWR
    ARWR: Summary for Arrowhead Research Corporation- Yahoo! Finance

    In a new study, researchers take a fresh approach to treating obesity by developing a peptide-like molecule that targets the blood vessels that feed fat tissue. They test their peptidomimetic called adipotide in obese monkeys and show that it both reduces fat tissue and decreases resistance to insulin.

    Adipotide is a short peptide-based agent that selectively targets a receptor expressed by the vascular endothelial cells that comprise the blood vessels that support subcutaneous and visceral fat. This peptidomimetic carries a molecule that, once internalized by the endothelial cells, causes them to undergo programmed cell death, thereby inducing gradual elimination of excess fat.

    In placebo-controlled experiments, spontaneously obese rhesus monkeys treated with adipotide for 28 days showed a 7 to 15% weight loss as well as improved insulin resistance. Two forms of imaging revealed that the weight loss occurred primarily through a reduction in fat tissue and did not reflect fluid loss or muscle wasting. Monkeys treated with adipotide displayed a 38% reduction in total body fat and a 27% reduction in abdominal fat compared to pretreatment baseline values.

    Early weight loss drug candidates are typically screened in rodent models of obesity. However, the central nervous system control and metabolic regulation of food intake and fat storage in rodents is quite different from that of monkeys and humans. Spontaneously obese monkeys are a more accurate model of obesity in humans and provide a valuable setting for testing anti-obesity drug candidates. Adipotide therapy resulted in a reduction in body mass, an improvement in insulin resistance, and a decrease in abdominal circumference, key predictors of diabetes in humans. These encouraging results support the further development of adipotide as a potential new prototype drug to combat obesity in humans.


    Barnhart KF, Christianson DR, Hanley PW, et al. A Peptidomimetic Targeting White Fat Causes Weight Loss and Improved Insulin Resistance in Obese Monkeys. Science Translational Medicine 2011;3(108):108ra12. A Peptidomimetic Targeting White Fat Causes Weight Loss and Improved Insulin Resistance in Obese Monkeys / Arap-Pasqualini Laboratory - Publications - MD Anderson Cancer Center

    Obesity, defined as body mass index greater than 30, is a leading cause of morbidity and mortality and a financial burden worldwide. Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. Biological differences between rodents and primates are a major hurdle for translation of anti-obesity strategies either discovered or developed in rodents into effective human therapeutics. Here, we evaluate the ligand-directed peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2 (henceforth termed adipotide) in obese Old World monkeys. Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys. Magnetic resonance imaging and dual-energy x-ray absorptiometry confirmed a marked reduction in white adipose tissue. At experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans.
     

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