Reversal of obesity by targeted ablation of adipose tissue.

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  • Author(s): Kolonin MG;Kolonin MG; Saha PK; Chan L; Pasqualini R; Arap W
  • Source:
    Nature medicine [Nat Med] 2004 Jun; Vol. 10 (6), pp. 625-32. Date of Electronic Publication: 2004 May 09.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1078-8956 (Print) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
    • Publication Information:
      Publication: New York Ny : Nature Publishing Company
      Original Publication: New York, NY : Nature Pub. Co., [1995-
    • Subject Terms:
      Adipose Tissue/*blood supply ; Apoptosis/*physiology ; Blood Vessels/*metabolism ; Obesity/*therapy ; Peptides/*therapeutic use; Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Amino Acid Sequence ; Animals ; Diet ; Energy Metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Peptide Library ; Peptides/metabolism ; Prohibitins ; Repressor Proteins/metabolism
    • 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.
    • Comments:
      Comment in: Nat Med. 2004 Jun;10(6):581-2. (PMID: 15170200)
    • Grant Information:
      CA078512 United States CA NCI NIH HHS; CA103042 United States CA NCI NIH HHS; CA82976 United States CA NCI NIH HHS; CA88106 United States CA NCI NIH HHS; CA90270 United States CA NCI NIH HHS; CA90810 United States CA NCI NIH HHS; HL51586 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Peptide Library)
      0 (Peptides)
      0 (Prohibitins)
      0 (Repressor Proteins)
    • Publication Date:
      Date Created: 20040511 Date Completed: 20040728 Latest Revision: 20220317
    • Publication Date:
      20240104
    • Accession Number:
      10.1038/nm1048
    • Accession Number:
      15133506