Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight

Dong-Hun Kim, Stephen C. Woods, Randy J. Seeley

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)907-915
Number of pages9
JournalDiabetes
Volume59
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1
Externally publishedYes

Fingerprint

Endothelium
Adipose Tissue
High Fat Diet
Eating
Body Weight
Apoptosis
Peptides
Leptin
Energy Metabolism
Appetite Regulation
Obese Mice
White Adipose Tissue
Neurosecretory Systems
Neuropeptide Y
Energy Intake
Research Design
Obesity
Fats
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight. / Kim, Dong-Hun; Woods, Stephen C.; Seeley, Randy J.

In: Diabetes, Vol. 59, No. 4, 01.04.2010, p. 907-915.

Research output: Contribution to journalArticle

Kim, Dong-Hun ; Woods, Stephen C. ; Seeley, Randy J. / Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight. In: Diabetes. 2010 ; Vol. 59, No. 4. pp. 907-915.
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