2024-11-12 ラトガース大学
<関連情報>
- https://www.rutgers.edu/news/researchers-suggest-stress-hormones-explain-how-obesity-causes-diabetes
- https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00376-0
過栄養は交感神経系の活動の増加によりインスリン抵抗性と代謝障害を引き起こすOvernutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity
Kenichi Sakamoto∙ Mary A. Butera∙ Chunxue Zhou∙ … ∙ Gary J. Schwartz∙ Azeddine Tahiri∙ Christoph Buettner
Cell Metabolism Published:October 21, 2024
DOI:https://doi.org/10.1016/j.cmet.2024.09.012
Graphical abstract
Highlights
•HFD feeding rapidly impairs insulin action by increasing SNS activity (SNA)
•Reducing SNA prevents HFD-induced insulin resistance and metabolic disorder
•Early HFD induces insulin resistance before cellular insulin signaling is impaired
•Lipolysis is a key mechanism through which elevated SNA induces insulin resistance
Summary
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.
