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bioRxiv · 10.1101/2020.06.06.137273

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

Cui, X.·Jing, J.·Wu, R.·Cao, Q.·Li, F.·Li, K.·Wang, S.·Yu, L.·Schwartz, G. J.·Shi, H.·Xue, B.
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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 novel fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NTF3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NTF3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NTF3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NTF3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC+/-). Increasing NTF3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC+/- mice or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NTF3 is an important fat-derived neurotrophic factor regulating SNS innervation, energy metabolism and obesity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Cui, X., Jing, J., Wu, R., Cao, Q., Li, F., Li, K., Wang, S., Yu, L., Schwartz, G. J., Shi, H., Xue, B.. 2020-06-07. Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue. https://doi.org/10.1101/2020.06.06.137273

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