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

Abstract

Physiological regulation of hypothalamic IL-1 gene expression by leptin and glucocorticoids: implications for energy homeostasis. Am J Physiol Endocrinol Metab 287: E1107–E1113, 2004. First published August 10, 2004; doi:10.1152/ajpendo.00038. 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