Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.
Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.
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Neuregulin4作用于下丘脑ErBb4以兴奋催产素神经元并保持代谢稳态。
DOI：
10.1002/advs.202204824
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发表时间：
2023-06
期刊：
影响因子：
15.1
通讯作者：
Hu, Cheng
中科院分区：
文献类型：
--
作者：
Zhang, Yi;Zhu, Yangyang;Wang, Jinghui;Jin, Li;Guo, Mingwei;Chen, Liwei;Zhang, Lina;Li, Yangyang;Wan, Baocheng;Zhang, Rong;Jia, Weiping;Hu, Cheng
Neuregulin 4 (Nrg4) is an adipose tissue‐enriched secreted factor that modulates glucose and lipid metabolism. Nrg4 is closely associated with obesity and preserves diet‐induced metabolic disorders. However, the specific mechanisms via which Nrg4 regulates metabolic homeostasis remain incompletely understood. Here, this work finds that the Nrg4 receptor, ErbB4, is highly expressed in the hypothalamus, and the phosphorylation of hypothalamic ErbB4 is reduced in diet‐induced obesity (DIO) mice. Peripheral Nrg4 can act on ErbB4 via blood circulation and excite neurons in the paraventricular nucleus of hypothalamus (PVN). Central administration of recombinant Nrg4 protein (rNrg4) reduces obesity and related metabolic disorders by influencing energy expenditure and intake. Overexpression of ErbB4 in the PVN protects against obesity, whereas its knock down in oxytocin (Oxt) neuron accelerates obesity. Furthermore, Nrg4‐ErbB4 signaling excites Oxt release, and ablation of Oxt neuron considerably attenuates the effect of Nrg4 on energy balance. These data suggest that the hypothalamus is a key target of Nrg4, which partially explains the multifaceted roles of Nrg4 in metabolism. Nrg4 secreted by adipose tissues can act on the ErbB4 receptor of oxytocin neurons in the hypothalamus and promote release of oxytocin peptide. Central administration of rNrg4 ameliorates dietary obesity by reducing appetite and increasing energy expenditure. This work highlights central Nrg4‐ErbB4 signaling as a potential therapeutic strategy for the treatment of obesity and related diseases.
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