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Hereditas(Beijing) ›› 2023, Vol. 45 ›› Issue (2): 144-155.doi: 10.16288/j.yczz.22-302

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Adipocyte reconstitution of Npy4r gene in Npy4r silenced mice promotes diet-induced obesity

Lan Wang(), Fan Zeng, Rongfeng Huang, Shu Lin, Zhihui Zhang, Min-Dian Li()   

  1. Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
  • Received:2022-10-13 Revised:2023-01-30 Online:2023-02-20 Published:2023-02-03
  • Contact: Li Min-Dian E-mail:770944509@qq.com;mindianli@tmmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(81900776)

Abstract:

Neural regulation of adipose tissue is crucial in the homeostasis of energy metabolism. Adipose tissue neuropeptide Y (NPY) and its receptors contribute to the development of diet-induced obesity. NPY1R and NPY2R are major receptors for NPY in peripheral tissues including the adipose tissue. NPY receptor 4 (Npy4r) gene is expressed in adipose tissue. However, it is unknown whether Npy4r is involved in the development of diet-induced obesity. Here, we established an immunofluorescence microscopy technique and generated an adipocyte-reconstituted Npy4r gene knockout mouse. Among six adipose depots, we found that NPY is highly expressed around the vasculature in a dot-like fashion in interscapular brown fat and subcutaneous fat, and NPY receptors are expressed in a depot-specific manner. NPY1R is highly expressed in epidydimal fat, interscapular and peri-aortic brown fat, NPY2R in both interscapular and peri-aortic brown fat, and NPY4R in both brown fat and epidydimal fat. Next, we showed that adipocyte-reconstituted expression of Npy4r promoted diet-induced obesity in mice (P < 0.0001). Overall, this study defines the abundance and distribution of NPY and its receptors 1, 2, and 4 in mouse adipose depots, and demonstrates in an adipocyte-reconstituted gene knockout model that adipocyte Npy4r is sufficient to promote diet-induced obesity.

Key words: Conditionally reconstituted gene knockout, loxP-STOP-loxP, adipocyte, adipose tissue, obesity