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Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue

Author

Listed:
  • Xin Cui

    (Georgia State University)

  • Jia Jing

    (Georgia State University)

  • Rui Wu

    (Georgia State University)

  • Qiang Cao

    (Georgia State University)

  • Fenfen Li

    (Georgia State University)

  • Ke Li

    (Georgia State University)

  • Shirong Wang

    (Georgia State University)

  • Liqing Yu

    (University of Maryland School of Medicine)

  • Gary Schwartz

    (Albert Einstein College of Medicine)

  • Huidong Shi

    (Georgia Cancer Center, Augusta University
    Medical College of Georgia, Augusta University)

  • Bingzhong Xue

    (Georgia State University)

  • Hang Shi

    (Georgia State University)

Abstract

Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NT-3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NT-3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NT-3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NT-3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC +/−). Increasing NT-3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC + /− or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NT-3 is a fat-derived neurotrophic factor that regulates SNS innervation, energy metabolism and obesity.

Suggested Citation

  • Xin Cui & Jia Jing & Rui Wu & Qiang Cao & Fenfen Li & Ke Li & Shirong Wang & Liqing Yu & Gary Schwartz & Huidong Shi & Bingzhong Xue & Hang Shi, 2021. "Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25766-2
    DOI: 10.1038/s41467-021-25766-2
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    Cited by:

    1. Xun Huang & Xinmeng Li & Hongyu Shen & Yiheng Zhao & Zhao Zhou & Yushuang Wang & Jingfei Yao & Kaili Xue & Dongmei Wu & Yifu Qiu, 2023. "Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Xu Feng & Liwen Wang & Ruoyu Zhou & Rui Zhou & Linyun Chen & Hui Peng & Yan Huang & Qi Guo & Xianghang Luo & Haiyan Zhou, 2023. "Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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