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脂肪组织衍生神经营养因子 3 调节脂肪组织中的交感神经支配和产热。

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

机构信息

Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

出版信息

Nat Commun. 2021 Sep 10;12(1):5362. doi: 10.1038/s41467-021-25766-2.

DOI:10.1038/s41467-021-25766-2
PMID:34508100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8433218/
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.

摘要

棕色脂肪产热的激活会增加能量消耗并减轻肥胖。交感神经系统（SNS）在棕色/米色脂肪细胞产热中很重要。在这里，我们发现一种脂肪衍生的“脂肪因子”神经营养因子神经营养因子 3（NT-3）及其受体原肌球蛋白受体激酶 C（TRKC）是脂肪组织中 SNS 生长和神经支配的关键调节剂。NT-3 在棕色/米色脂肪细胞中高度表达，并强烈刺激交感神经元轴突生长。NT-3/TRKC 调节神经元轴突生长和伸长的众多途径。脂肪组织交感神经支配在脂肪细胞特异性 NT-3 过表达的小鼠中显著增加，但在 TRKC 杂合不足（TRKC+/-）的小鼠中显著减少。通过药理学或遗传方法增加 NT-3 可促进米色脂肪细胞的发育，增强冷诱导产热并预防饮食诱导的肥胖（DIO）；而 TRKC+/- 或 SNS TRKC 缺陷小鼠不耐寒，容易发生 DIO。因此，NT-3 是一种脂肪衍生的神经营养因子，可调节 SNS 神经支配、能量代谢和肥胖。

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