能量稳态
下丘脑
内分泌学
内科学
神经肽
生物
调节器
转录因子
平衡
胰岛素抵抗
细胞生物学
神经肽Y受体
胰岛素
肥胖
医学
受体
生物化学
基因
作者
Yatong Fan,Sufang Sheng,Cunle Guo,Wei Qiao,Jin Ye,Lu Tan,Yong Gao,Lei Zhang,Dong Xi,Jun Zhang,Xiaorong Li,Hui Shen,Yunfei Liao,Yongsheng Chang
出处
期刊:Diabetes
[American Diabetes Association]
日期:2022-07-20
摘要
The neuropeptide AgRP is essential for maintaining systemic energy homeostasis. In the current study, we show that hypothalamic Foxi2, as a novel regulator of nutrient sensing, controls systemic energy metabolism by specifically stimulating AgRP expression. Foxi2 was highly expressed in the hypothalamus, and its expression was induced by fasting. Immunofluorescence assays demonstrated that Foxi2 was localized in AgRP neurons. We stereotactically injected adeno-associated virus to selectively overexpress Foxi2 in AgRP-IRES-Cre mice and found that Foxi2 overexpression in AgRP neurons specifically increased AgRP expression, thereby increasing food intake and reducing energy expenditure, subsequently leading to obesity and insulin resistance. Mechanistically, Foxi2 stimulated AgRP expression by directly binding to it and activating its transcription. Furthermore, Foxi2 overexpression activated AgRP neuron activity, as revealed by whole-cell patch-clamp experiments. Conversely, global Foxi2-mutant mice became leaner with age and were resistant to high-fat diet-induced obesity and metabolic disturbances. Collectively, our data suggest that Foxi2 plays an important role in controlling energy metabolism by regulating AgRP expression.
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