Reversal of obesity by targeted ablation of adipose tissue.
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.
Kolonin
Mikhail G
MG
The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Saha
Pradip K
PK
Chan
Lawrence
L
Pasqualini
Renata
R
Arap
Wadih
W
D000273:Adipose Tissue / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001808:Blood Vessels / Q000378:metabolism*; D004032:Diet; D004734:Energy Metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000628:therapy*; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism / Q000627:therapeutic use*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000378:metabolism
D019151:Peptide Library; D010455:Peptides; D000091402:Prohibitins; D012097:Repressor Proteins