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

Physiological regulation of hypothalamic IL-1beta gene expression by leptin and glucocorticoids: implications for energy homeostasis.
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瘦素和糖皮质激素对下丘脑 IL-1β 基因表达的生理调节:对能量稳态的影响。

DOI:
10.1152/ajpendo.00038.2004
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发表时间:
2004
期刊:
American journal of physiology. Endocrinology and metabolism.
影响因子:
--
通讯作者:
Schwartz,MichaelW
Schwartz,MichaelW
中科院分区:
--
文献类型:
--
作者:
Wisse,BrentE;Ogimoto,Kayoko;Morton,GregoryJ;Wilkinson,CharlesW;Frayo,RScott;Cummings,DavidE;Schwartz,MichaelW

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白细胞介素-1 β(IL-1β)在多种组织中合成,包括下丘脑,在那里它参与控制食物摄入。目前的研究旨在探讨下丘脑IL-1β基因表达是否受到瘦素和糖皮质激素(GC)(参与能量稳态的关键激素)的生理调节。肾上腺切除术(ADX)使下丘脑IL-1β mRNA水平增加两倍(与假手术对照组相比P< 0.05),皮下输注生理剂量的皮质酮可阻断该作用。相反,30%infa/fa(Zucker)大鼠下丘脑IL-1β mRNA水平降低,这是一种由瘦素受体突变引起的遗传性肥胖模型(P= 0.01 vs.瘦型同窝仔),ADX增加infa/farats下丘脑IL-1β mRNA水平的作用(P= 0.02)与正常动物相似。此外,禁食48 h(降低瘦素水平,升高皮质酮水平)使下丘脑IL-1β mRNA水平降低30%(P= 0.02),再喂食12 h后,这种降低完全逆转。因此,瘦素和GC对下丘脑IL-1β基因表达产生相反的作用,并且皮质酮在存在和不存在完整瘦素信号传导的情况下都发挥限制该细胞因子表达的生理作用。与这一假设一致,正常大鼠全身给予瘦素(2 mg/kg ip)可使下丘脑IL-1β mRNA水平增加2倍(P< 0.05 vs.溶媒),其作用与ADX相似。这些数据支持下丘脑IL-1β的表达受皮质酮和瘦素的相反生理调节的模型。
Interleukin-1β (IL-1β) 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-1β gene expression is subject to physiological regulation by leptin and glucocorticoids (GCs), key hormones involved in energy homeostasis. Adrenalectomy (ADX) increased hypothalamic IL-1β 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-1β mRNA levels were reduced by 30% infa/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-1β mRNA levels infa/farats (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-1β 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-1β 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-1β 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-1β is subject to opposing physiological regulation by corticosterone and leptin.
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