Peptide Designed to Elicit Apoptosis in Adipose Tissue Endothelium Reduces Food Intake and Body Weight

  1. Randy J. Seeley1
  1. 1Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio;
  2. 2Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio.
  1. Corresponding author: Randy J. Seeley, randy.seeley{at}uc.edu.

Abstract

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.

RESEARCH DESIGN AND 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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received July 31, 2009.
    • Accepted January 6, 2010.

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  1. Diabetes vol. 59 no. 4 907-915
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