Narimatsu Yuki, Kato Masaki, Iwakoshi-Ukena Eiko, Moriwaki Shogo, Ogasawara Ayano, Furumitsu Megumi, Ukena Kazuyoshi
Laboratory of Neurometabolism, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8521, Japan.
Biomedicines. 2023 Dec 6;11(12):3230. doi: 10.3390/biomedicines11123230.
Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of led to fat accumulation without increased food consumption in male NPGM-Cre mice. Chemogenetic activation of NPGM neurons in the hypothalamus acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis.
肥胖会诱发下丘脑和脂肪组织的炎症，从而导致代谢紊乱。一种新的下丘脑神经肽，神经分泌蛋白GM（NPGM），先前已在脊椎动物的下丘脑中被鉴定出来。虽然NPGM在雏鸡的脂质代谢中起重要作用，但其在哺乳动物中的代谢调节作用仍不清楚。在本研究中，构建了一种新型的Cre驱动系NPGM-Cre，用于细胞特异性操作。在雄性NPGM-Cre小鼠中，Cre依赖性过表达导致脂肪堆积，而食物摄入量并未增加。下丘脑NPGM神经元的化学遗传激活急性促进摄食行为，并长期导致体重增加出现短暂上升。此外，被消融的NPGM神经元表现出葡萄糖不耐受的倾向，同时促炎巨噬细胞浸润到脂肪组织中。这些结果表明，NPGM神经元可能调节脂质储存和炎症反应，从而维持葡萄糖稳态。
