A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance.

A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance.
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DOI:
10.1038/srep26830
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发表时间:
2016-05-26
期刊:
影响因子:
4.6
通讯作者:
Morgan PJ
Morgan PJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Helfer G;Ross AW;Thomson LM;Mayer CD;Stoney PN;McCaffery PJ;Morgan PJ

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体重的长期和可逆变化是季节性动物的典型特征。下丘脑伸展细胞和室管膜细胞中的甲状腺激素(TH)和维甲酸(RA)与光周期反应有关。我们研究了RA下游的信号以及这如何与光周期F344大鼠的体重和食物摄入量的控制有关。Chmerin是一种炎性趋化因子,在能量代谢中具有已知的作用,被确定为RA的靶标。趋化蛋白(Rarres2)及其受体的基因表达定位于伸展细胞和室管膜细胞,在长光周期(LD)下的表达高于短光周期(SD),表明其具有生理作用。大鼠脑室注射趋化蛋白2周,模拟SD向LD的转变(摄食量增加)。Chmerin还增加了细胞骨架蛋白Vimentin的表达,暗示下丘脑在这一反应中重塑。相比之下,在12 h:12 h的光周期下,急性脑室注射趋化因子抑制摄食量,减轻体重,并伴随24 h后参与生长和摄食的下丘脑神经肽的相关变化。我们将下丘脑室带描述为神经内分泌调节的关键部位,在那里,炎症信号趋化蛋白将TH和RA信号与下丘脑重塑联系起来。
Long-term and reversible changes in body weight are typical of seasonal animals. Thyroid hormone (TH) and retinoic acid (RA) within the tanycytes and ependymal cells of the hypothalamus have been implicated in the photoperiodic response. We investigated signalling downstream of RA and how this links to the control of body weight and food intake in photoperiodic F344 rats. Chemerin, an inflammatory chemokine, with a known role in energy metabolism, was identified as a target of RA. Gene expression of chemerin (Rarres2) and its receptors were localised within the tanycytes and ependymal cells, with higher expression under long (LD) versus short (SD) photoperiod, pointing to a physiological role. The SD to LD transition (increased food intake) was mimicked by 2 weeks of ICV infusion of chemerin into rats. Chemerin also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response. By contrast, acute ICV bolus injection of chemerin on a 12 h:12 h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24 hr. We describe the hypothalamic ventricular zone as a key site of neuroendocrine regulation, where the inflammatory signal, chemerin, links TH and RA signaling to hypothalamic remodeling.