Appetite suppression and weight reduction by a centrally active aminosterol

Rexford S Ahima, Hiralben R. Patel, Nobuhiko Takahashi, Yong Qi, Stanley M. Hileman, Michael A. Zasloff

Research output: Contribution to journalArticle

Abstract

The rise in obesity and its complications has generated enormous interest in the regulation of feeding and body weight. We show that a spermine metabolite of cholesterol (MSI-1436) decreases body weight, specifically fat, by suppressing feeding and preventing the reduction in energy expenditure, hormonal changes, and patterns of neuropeptide expression normally associated with weight loss. MSI-1436 enters the brain after peripheral injection and is more potent when injected into the cerebral ventricle (intracerebroventricular [ICV]). Systemic or ICV MSI-1436 administration induced similar patterns of Fos immunoreactivity in the brain, especially the paraventricular hypothalamic nucleus (PVN). This brain region integrates neural signals from hypothalamic and brain stem nuclei and regulates feeding behavior, autonomic function, and neuroendocrine function. Microinjection of MSI-1436 into the PVN potently suppressed feeding and reduced body weight for several days. Unlike caloric restriction, MSI-1436 decreased mRNA levels of agouti-related peptide and neuropeptide Y in the hypothalamus. These findings indicate that MSI-1436 acts in the brain to regulate food intake and energy expenditure, likely through suppression of orexigenic hypothalamic pathways.

Original languageEnglish (US)
Pages (from-to)2099-2104
Number of pages6
JournalDiabetes
Volume51
Issue number7
StatePublished - 2002
Externally publishedYes

Fingerprint

Appetite
Weight Loss
Paraventricular Hypothalamic Nucleus
Body Weight
Brain
Energy Metabolism
Cerebral Ventricles
Caloric Restriction
Spermine
Neuropeptide Y
Microinjections
Feeding Behavior
Neuropeptides
Hypothalamus
Brain Stem
24-dihydroxy-5-cholestane 24-sulfate 3-N-1(spermine)-7
Obesity
Eating
Fats
Cholesterol

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Ahima, R. S., Patel, H. R., Takahashi, N., Qi, Y., Hileman, S. M., & Zasloff, M. A. (2002). Appetite suppression and weight reduction by a centrally active aminosterol. Diabetes, 51(7), 2099-2104.

Appetite suppression and weight reduction by a centrally active aminosterol. / Ahima, Rexford S; Patel, Hiralben R.; Takahashi, Nobuhiko; Qi, Yong; Hileman, Stanley M.; Zasloff, Michael A.

In: Diabetes, Vol. 51, No. 7, 2002, p. 2099-2104.

Research output: Contribution to journalArticle

Ahima, RS, Patel, HR, Takahashi, N, Qi, Y, Hileman, SM & Zasloff, MA 2002, 'Appetite suppression and weight reduction by a centrally active aminosterol', Diabetes, vol. 51, no. 7, pp. 2099-2104.
Ahima RS, Patel HR, Takahashi N, Qi Y, Hileman SM, Zasloff MA. Appetite suppression and weight reduction by a centrally active aminosterol. Diabetes. 2002;51(7):2099-2104.
Ahima, Rexford S ; Patel, Hiralben R. ; Takahashi, Nobuhiko ; Qi, Yong ; Hileman, Stanley M. ; Zasloff, Michael A. / Appetite suppression and weight reduction by a centrally active aminosterol. In: Diabetes. 2002 ; Vol. 51, No. 7. pp. 2099-2104.
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