Adipose vascular endothelial growth factor B is a major regulator of energy metabolism

in Journal of Endocrinology
Authors:
Yang Chen Transgenic Research Center, Northeast Normal University, Changchun, China

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Mingyue Zhao Transgenic Research Center, Northeast Normal University, Changchun, China

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Chenhao Wang Transgenic Research Center, Northeast Normal University, Changchun, China

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Huaizhen Wen Transgenic Research Center, Northeast Normal University, Changchun, China

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Yuntao Zhang Transgenic Research Center, Northeast Normal University, Changchun, China

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Mingxu Lu Transgenic Research Center, Northeast Normal University, Changchun, China

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Salah Adlat Transgenic Research Center, Northeast Normal University, Changchun, China

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Tingting Zheng Transgenic Research Center, Northeast Normal University, Changchun, China

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Mingjiao Zhang Transgenic Research Center, Northeast Normal University, Changchun, China

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Dan Li Transgenic Research Center, Northeast Normal University, Changchun, China

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Xiaodan Lu Transgenic Research Center, Northeast Normal University, Changchun, China

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Mengwei Guo Transgenic Research Center, Northeast Normal University, Changchun, China

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Hongyu Chen Transgenic Research Center, Northeast Normal University, Changchun, China

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Luqing Zhang Transgenic Research Center, Northeast Normal University, Changchun, China
Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China

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Xuechao Feng Transgenic Research Center, Northeast Normal University, Changchun, China
Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China

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Yaowu Zheng Transgenic Research Center, Northeast Normal University, Changchun, China
Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China

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Correspondence should be addressed to Y Zheng: zhengyw442@nenu.edu.cn

*(Y Chen and M Zhao contributed equally to this work)

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Excessive fat accumulation causes obesity and many diseases. Previous study demonstrates VEGFB universal knockout induces obese phenotypes including expansion of white adipose tissue, whitening of brown adipose tissue, increase of fat accumulation and reduction in energy consumption. However, roles of VEGFB in adipose tissues are not clear. In this study, we have generated a mouse model with adipose-specific VEGFB repression using CRISPR/dCas9 system (Vegfb AdipoDown ) and investigated the roles of VEGFB in adipose development and energy metabolism. VEGFB repression induced significant changes in adipose tissue structure and function. Vegfb AdipoDown mice have larger body sizes, larger volume of white adipose tissues than its wild type littermates. Adipose-specific VEGFB repression induced morphological and functional transformation of adipose tissues toward white adipose for energy storage. Metabolic processes are broadly changed in Vegfb AdipoDown adipose tissues including carbohydrate metabolism, lipid metabolism, nucleotide metabolism and amino acid metabolism. We have demonstrated that adipose VEGFB repression can recapitulate most of the phenotypes of the whole body VEGFB knockout mouse. Intriguingly, approximately 50% VEGFB repression in adipose tissues can almost completely mimic the effects of universal Vegfb deletion, suggesting adipose VEGFB is a major regulator of energy metabolism and may be important in prevention and treatment of obesity.

Supplementary Materials

    • Supporting Information
    • Supplemental figure1
    • Supplemental figure2
    • Supplemental Table 1. Primer sequences used for plasmid construction
    • Supplemental Table 2. Primer sequences for real-time PCR

 

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