Hypothalamic agouti-related peptide neurons and the central melanocortin system are crucial mediators of leptin's antidiabetic actions.
Hypothalamic agouti-related peptide neurons and the central melanocortin system are crucial mediators of leptin's antidiabetic actions.
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DOI：
10.1016/j.celrep.2014.04.010
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发表时间：
2014-05-22
期刊：
影响因子：
8.8
通讯作者：
Bjørbæk C
中科院分区：
文献类型：
--
作者：
Gonçalves GH;Li W;Garcia AV;Figueiredo MS;Bjørbæk C
The adipocyte hormone leptin has potent beneficial effects on glucose metabolism via actions in the arcuate nucleus of the hypothalamus (ARC). However, the requirement of specific subgroups of neurons within the ARC in mediating leptin's anti-diabetic actions is unknown. Here we generated diabetic Lepob/ob or Leprdb/db mice lacking or re-expressing leptin receptors only in selected subgroups of neurons to test the sufficiency and requirement of these neurons in the glucose-lowering effects of leptin. Our results show that agouti-related peptide (AgRP)-expressing neurons are both required and sufficient to normalize serum glucose levels by leptin. Leptin receptors in pro-opiomelanocortin (POMC) neurons or SF1 neurons are not required. Furthermore, glucose normalization by leptin is blunted in diabetic Lepob/ob;MC4R-null mice, but not in Lepob/ob mice lacking NPY or GABA in AgRP neurons. Collectively, our data suggests that AgRP neurons play a key role in mediate the glucose-lowering actions of leptin and that these beneficial actions require the melanocortin system, but not NPY and GABA.
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影响因子：
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作者：
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通讯作者：
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