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) Gene Expression by Leptin and Glucocorticoids: Implications for Energy Homeostasis
1 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA, USA
2 Geriatric Research, Education and Clinical Center, Vetarans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA
3 Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA
* To whom correspondence should be addressed. E-mail: bewisse{at}u.washington.edu.
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,
measured by real-time PCR, by two fold (p<0.05 vs. sham-operated controls) and this
effect was blocked by sc 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 due to 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 48h (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 re-feeding for 12h. 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 (2mg/kg IP) increased hypothalamic IL-1 mRNA levels by two fold (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.
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 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]
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