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      Reversal of obesity by targeted ablation of adipose tissue.

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          Abstract

          Obesity is an increasingly prevalent human condition in developed societies. Despite major progress in the understanding of the molecular mechanisms leading to obesity, no safe and effective treatment has yet been found. Here, we report an antiobesity therapy based on targeted induction of apoptosis in the vasculature of adipose tissue. We used in vivo phage display to isolate a peptide motif (sequence CKGGRAKDC) that homes to white fat vasculature. We show that the CKGGRAKDC peptide associates with prohibitin, a multifunctional membrane protein, and establish prohibitin as a vascular marker of adipose tissue. Targeting a proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat. Resorption of established white adipose tissue and normalization of metabolism resulted in rapid obesity reversal without detectable adverse effects. Because prohibitin is also expressed in blood vessels of human white fat, this work may lead to the development of targeted drugs for treatment of obese patients.

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          Author and article information

          Journal
          Nat Med
          Nature medicine
          Springer Science and Business Media LLC
          1078-8956
          1078-8956
          Jun 2004
          : 10
          : 6
          Affiliations
          [1 ] The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
          Article
          nm1048
          10.1038/nm1048
          15133506
          1c54c071-c714-4d8d-bebe-4631ff250a2e
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