HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/E1107    most recent 00038.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Wisse, B. E. Articles by Schwartz, M. W. Search for Related Content PubMed PubMed Citation Articles by Wisse, B. E. Articles by Schwartz, M. W.

Physiological regulation of hypothalamic IL-1 gene expression by leptin and glucocorticoids: implications for energy homeostasis

¹Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Harborview Medical Center, Seattle 98104; ²Department of Medicine, and ³Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington 98108

Submitted 27 January 2004 ; accepted in final form 2 August 2004

Interleukin-1 (IL-1) is synthesized in a variety of tissues, including the hypothalamus, where it is implicated in the control of food intake. The current studies were undertaken to investigate whether hypothalamic IL-1 gene expression is subject to physiological regulation by leptin and glucocorticoids (GCs), key hormones involved in energy homeostasis. Adrenalectomy (ADX) increased hypothalamic IL-1 mRNA levels twofold, measured by real-time PCR (P < 0.05 vs. sham-operated controls), and this effect was blocked by subcutaneous infusion of a physiological dose of corticosterone. Conversely, hypothalamic IL-1 mRNA levels were reduced by 30% in fa/fa (Zucker) rats, a model of genetic obesity caused by leptin receptor mutation (P = 0.01 vs. lean littermates), and the effect of ADX to increase hypothalamic IL-1 mRNA levels in fa/fa rats (P = 0.02) is similar to that seen in normal animals. Moreover, fasting for 48 h (which lowers leptin and raises corticosterone levels) reduced hypothalamic IL-1 mRNA levels by 30% (P = 0.02), and this decrease was fully reversed by refeeding for 12 h. Thus leptin and GCs exert opposing effects on hypothalamic IL-1 gene expression, and corticosterone plays a physiological role to limit expression of this cytokine in both the presence and absence of intact leptin signaling. Consistent with this hypothesis, systemic leptin administration to normal rats (2 mg/kg ip) increased hypothalamic IL-1 mRNA levels twofold (P < 0.05 vs. vehicle), an effect similar to that of ADX. These data support a model in which expression of hypothalamic IL-1 is subject to opposing physiological regulation by corticosterone and leptin.

interleukin-1; cytokine; corticosterone; food intake; appetite; obesity; anorexia

This article has been cited by other articles:

				M. C. Garcia, I. Wernstedt, A. Berndtsson, M. Enge, M. Bell, O. Hultgren, M. Horn, B. Ahren, S. Enerback, C. Ohlsson, et al. Mature-onset obesity in interleukin-1 receptor I knockout mice. Diabetes, May 1, 2006; 55(5): 1205 - 1213. [Abstract] [Full Text] [PDF]

				Y. Nishida, M. Yoshioka, and J. St-Amand Regulation of hypothalamic gene expression by glucocorticoid: implications for energy homeostasis Physiol Genomics, March 13, 2006; 25(1): 96 - 104. [Abstract] [Full Text] [PDF]