PTEN regulates vagal-insulin signaling to optimize autonomic output determining peripheral inflammatory and metabolic homeostasis.

ABSTRACT: The vagus nerve (VN) is a major component of the parasympathetic nervous system that regulates glucose and energy homeostasis. However, the specific molecular signaling pathways within the VN that regulates this homeostasis remain unclear. Here, we show that vagal neuron-specific deletion of phosphatase and tensin homolog (Pten), the endogenous negative regulator of PI3K, led to increased vagal output. Intriguingly, dopaminergic signaling genes were upregulated, correlating with elevated sympathetic nerve density and increased norepinephrine levels in adipose tissue of vagal Pten-deficient mice. These mice were also protected against high-fat diet-induced obesity, insulin resistance, and systemic inflammation. To investigate insulin-specific PI3K signaling within the VN, we generated mice

SUBMITTER: Li YZ 

PROVIDER: S-EPMC12824380 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature