Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.

Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.
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DOI:
10.1038/srep31849
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发表时间:
2016-08-23
期刊:
影响因子:
4.6
通讯作者:
Knauf C
Knauf C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Drougard A;Fournel A;Marlin A;Meunier E;Abot A;Bautzova T;Duparc T;Louche K;Batut A;Lucas A;Le-Gonidec S;Lesage J;Fioramonti X;Moro C;Valet P;Cani PD;Knauf C

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Apelin是一种参与能量代谢调控的生物活性肽。在下丘脑中,长期暴露于高水平的爱帕琳与肝葡萄糖产生的增加有关,然后导致2型糖尿病的发作。然而,目前尚不清楚慢性爱帕琳肽在脑中的有害作用以及对能量消耗和产热的后果背后的分子机制。我们的目的是评估慢性侧脑室(icv)输注apelin对正常小鼠下丘脑炎症基因表达、能量消耗、产热和棕色脂肪组织功能的影响。我们已经证明,慢性icv输注apelin增加了下丘脑中促炎因子的表达,这与血浆白细胞介素-1 β的增加有关。与此同时,输注icv爱帕琳的小鼠表现出显著较低的能量消耗,并伴有棕色脂肪组织中PGC 1 α、PRDM 16和UCP 1表达的降低,这可以解释这些小鼠产热的改变。这些数据提供了令人信服的证据表明,中枢爱帕琳蛋白通过改变能量消耗、产热和脂肪布朗宁而促进2型糖尿病的发展。
Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.