EphA3 deficiency in the hypothalamus promotes high-fat diet-induced obesity in mice

Jubiao Zhang ¹Yang Chen ¹Lihong Yan ¹Xin Zhang ¹Xiaoyan Zheng ²Junxia Qi ²Fen Yang ²Juxue Li³

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作者信息

1. State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing Medical University,Nanjing,Jiangsu 211166,China;The Affiliated Eye Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China
2. State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing Medical University,Nanjing,Jiangsu 211166,China
3. State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing Medical University,Nanjing,Jiangsu 211166,China;The Affiliated Eye Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China;The Second Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210011,China
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Abstract

Erythropoietin-producing hepatocellular carcinoma A3(EphA3)is a member of the largest subfamily of tyrosine kinase receptors—Eph receptors.Previous studies have shown that EphA3 is associated with tissue development.Recently,we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity(DIO).However,the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear.In the current study,we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding.Moreover,the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure.Knockdown of EphA3 leads to smaller intracellular vesicles in GT 1-7 cells.The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO.

Key words

EphA3/hypothalamus/metabolism/CRISPR-Cas9/obesity

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基金项目

National Natural Science Foundation of China(82070872)

National Natural Science Foundation of China(92049118)

National Natural Science Foundation of China(81570774)

Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(JSSCTD2021)

National Key Research and Development Program of China(2018YFC1003504)

Junior Thousand Talents Program of China,the NJMU startup fund()

出版年

2023

生物医学研究杂志(英文版)

南京医科大学

生物医学研究杂志(英文版)

CSCD北大核心

影响因子：0.794

ISSN：1674-8301

参考文献量30

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