Brain-liver interaction results in hepatic inflammation during obesity

Brain-liver interaction results in hepatic inflammation during obesity

Insulin directly controls glucose metabolism in various target organs such as skeletal muscle, adipose tissue, and the liver, while also acting indirectly on the CNS to regulate glucose/energy metabolism. In fact, brain-specific insulin receptor knockout mice display insulin resistance, in addition to increased food intake, body weight, and obesity. Various studies have indicated that central insulin action reduces hepatic glucose production (HGP), especially in rodents.

Central insulin action activates hepatic IL-6/STAT3 signaling, which suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear.

Researchers in the journal Cell Reports present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via α7-nicotinic acetylcholine receptors (α7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6/STAT3 signaling by suppressing vagal activity.

Indeed, central insulin-mediated hepatic IL-6/STAT3 activation and gluconeogenic gene suppression were impeded in mice with hepatic vagotomy, pharmacological cholinergic blockade, or α7-nAchR deficiency.

In high-fat diet-induced obese and insulin-resistant mice, control of the vagus nerve by central insulin action was disturbed, inducing a persistent increase of inflammatory cytokines.

These findings suggest that dysregulation of the α7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity.



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