A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys

Kirstin F. Barnhart, Dawn R. Christianson, Patrick W. Hanley, Wouter H.P. Driessen, Bruce J. Bernacky, Wallace B. Baze, Sijin Wen, Mei Tian, Jingfei Ma, Mikhail G. Kolonin, Pradip K. Saha, Kim Anh Do, James F. Hulvat, Juri G. Gelovani, Lawrence Chan, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number108ra112
JournalScience translational medicine
Volume3
Issue number108
DOIs
StatePublished - Nov 9 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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