Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight.
OBJECTIVE
Because adipose tissue is highly vascularized, modifying adipose tissue vasculature may provide a novel method for reducing body fat. A peptide sequence that elicits apoptosis of endothelium in white fat potently reduced body weight. We sought to determine how inhibiting adipose tissue vasculature changes key aspects of energy balance regulation and the neuroendocrine system that maintains energy balance.


METHODS
Lean and obese mice or rats were treated with proapoptotic peptide for 4 or 27 days. Daily energy intake and expenditure were measured in mice on a low- (LFD) or high-fat diet (HFD) and in rats on a HFD. A conditioned taste aversion test was performed to assess whether proapoptotic peptide produces visceral illness. Hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocoritin (POMC) mRNA expression and plasma leptin levels were evaluated.


RESULTS
Proapoptotic peptide completely reversed HFD-induced obesity in mice and reduced body weight in mice and rats on a HFD but not in those on a LFD. Fat loss occurred with no change of energy expenditure but reduced food intake that occurred without signs of illness and despite reduced circulating leptin and reduced hypothalamic POMC gene expression, indicating that the decrease in food intake is independent of the action of leptin.


CONCLUSIONS
These experiments provide compelling evidence for a previously unknown relationship between the status of adipose tissue vasculature and the regulation of food intake.
Kim
Dong-Hoon
DH
Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Woods
Stephen C
SC
Seeley
Randy J
RJ
D000273:Adipose Tissue / Q000098:blood supply* / Q000187:drug effects; D054369:Agouti-Related Protein / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001823:Body Composition; D001835:Body Weight / Q000187:drug effects; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D002149:Energy Intake / Q000187:drug effects / Q000235:genetics; D007031:Hypothalamus / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018919:Neovascularization, Physiologic; D009478:Neuropeptide Y / Q000235:genetics; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D054369:Agouti-Related Protein; D004041:Dietary Fats; D020738:Leptin; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin