The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus.
The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus.
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DOI：
10.1016/j.cmet.2014.07.022
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发表时间：
2014-10-07
期刊：
影响因子：
29
通讯作者：
Luckman SM
中科院分区：
文献类型：
--
作者：
Dodd GT;Worth AA;Nunn N;Korpal AK;Bechtold DA;Allison MB;Myers MG Jr;Statnick MA;Luckman SM
瘦素是一种重要的代谢调节因子，它作用于脑受体（Lepr）以减少能量摄入和增加能量消耗。一些介导瘦素的厌食作用的细胞通路被确定，但那些介导产热效应已被证明更难以破译。我们定义了下丘脑背内侧核（DMH）的神经元的人口含有RFamide PrRP，这是激活瘦素。在这些细胞中选择性地破坏Lepr阻断了对瘦素的产热反应并导致肥胖。相反，需要脑干中单独的瘦素不敏感PrRP神经元群体来实现肠源性激素胆囊收缩素（CCK）的饱腹作用。PrRP的整体缺失（在loxSTOPlox-PrRP小鼠中）导致肥胖和减弱对瘦素和CCK的应答。Cre重组酶介导的PrRP在脑干中的再激活挽救了CCK的厌食作用，但需要在下丘脑中的再激活来重新建立瘦素的产热作用。下丘脑背内侧核中的PrRP神经元对瘦素敏感细胞特异性Lepr KO阻断瘦素诱导的产热并导致肥胖PrRP的整体缺失减弱对瘦素和CCK的反应产热和饱腹感效应需要不同的PrRP群体瘦素作用于大脑以调节食物摄入和能量消耗。Dodd等人识别下丘脑背内侧的PrRP神经元群体，这些神经元直接对瘦素做出反应，以增加核心体温。相反，脑干中的PrRP神经元是肠源性胆囊收缩素的饱腹作用所必需的。
Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin’s anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin. PrRP neurons in the hypothalamic dorsomedial nucleus are sensitive to leptin Cell-specific Lepr KO blocks leptin-induced thermogenesis and causes obesity Global deletion of PrRP attenuates responses to leptin and CCK Distinct PrRP populations are needed for thermogenesis and satiety effects Leptin acts on the brain to regulate food intake and energy expenditure. Dodd et al. identify a population of PrRP neurons in the dorsomedial hypothalamus that directly respond to leptin to increase core body temperature. PrRP neurons in the brainstem are required, instead, for the satiating actions of gut-derived cholecystokinin.
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影响因子：
16.2
作者：
Dhillon, H;Zigman, JM;Lowelll, BB
通讯作者：
Lowelll, BB
DOI：
10.1523/jneurosci.0155-09.2009
发表时间：
2009-03-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Leshan RL;Louis GW;Jo YH;Rhodes CJ;Münzberg H;Myers MG Jr
通讯作者：
Myers MG Jr
DOI：
10.1006/bbrc.1995.1728
发表时间：
1995-05-25
影响因子：
3.1
作者：
FUNAKOSHI, A;MIYASAKA, K;KONO, A
通讯作者：
KONO, A
影响因子：
4.7
作者：
Dodd, Garron T.;Worth, Amy A.;Luckman, Simon M.
通讯作者：
Luckman, Simon M.
影响因子：
25
作者：
Lawrence, CB;Celsi, F;Luckman, SM
通讯作者：
Luckman, SM