美国罗格斯大学Christoph Buettner团队近期取得重要工作进展，他们研究提出，营养过剩通过增加交感神经系统活动导致胰岛素抵抗和代谢紊乱。相关研究成果2024年10月21日在线发表于《细胞—代谢》杂志上。

据介绍，肥胖诱导的胰岛素抵抗的机制仍然不完全清楚，因为受损的细胞胰岛素信号传导，传统上被认为是胰岛素抵抗的主要驱动因素，并不总是伴随着受损的胰岛素作用。营养过剩会迅速增加血浆去甲肾上腺素（NE），表明交感神经系统（SNS）过度激活。然而，SNS在肥胖中的作用是有争议的，因为SNS活动（SNA）的增加和减少都有报道。

研究人员表明，减少SNS中儿茶酚胺（CA）的释放可以预防营养过剩诱导的胰岛素抵抗以及高血糖症、脂肪组织功能障碍和脂肪肝疾病，正如利用酪氨酸羟化酶（th；THΔper）诱导性和外周限制性缺失的小鼠模型所证明的那样。SNA升高诱导胰岛素抵抗的一个关键机制是通过触发脂肪组织脂肪分解。SNA的增加是营养过剩诱导的胰岛素抵抗和代谢性疾病发病机制的关键驱动因素，与细胞胰岛素信号无关。

附：英文原文

Title: Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity

Author: Kenichi Sakamoto, Mary A. Butera, Chunxue Zhou, Giulia Maurizi, Bandy Chen, Li Ling, Adham Shawkat, Likhitha Patlolla, Kavira Thakker, Victor Calle, Donald A. Morgan, Kamal Rahmouni, Gary J. Schwartz, Azeddine Tahiri, Christoph Buettner

Issue&Volume: 2024-10-21

Abstract: The mechanisms underlying obesity-induced insulin resistance remain incompletely understood, as impaired cellular insulin signaling, traditionally considered the primary driver of insulin resistance, does not always accompany impaired insulin action. Overnutrition rapidly increases plasma norepinephrine (NE), suggesting overactivation of the sympathetic nervous system (SNS). However, the role of the SNS in obesity is controversial, as both increased and decreased SNS activity (SNA) have been reported. Here, we show that reducing catecholamine (CA) release from the SNS protects against overnutrition-induced insulin resistance as well as hyperglucagonemia, adipose tissue dysfunction, and fatty liver disease, as we demonstrate utilizing a mouse model of inducible and peripherally restricted deletion of tyrosine hydroxylase (th; THΔper). A key mechanism through which heightened SNA induces insulin resistance is by triggering adipose tissue lipolysis. Increased SNA emerges as a critical driver in the pathogenesis of overnutrition-induced insulin resistance and metabolic disease independent of cellular insulin signaling.

DOI: 10.1016/j.cmet.2024.09.012

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00376-0