| First Author | Kimura K | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 10 | Pages | 2362-74 |
| PubMed ID | 26947072 | Mgi Jnum | J:234348 |
| Mgi Id | MGI:5789829 | Doi | 10.1016/j.celrep.2016.02.032 |
| Citation | Kimura K, et al. (2016) Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic Vagal Activation via the Nicotinic Alpha 7 Acetylcholine Receptor. Cell Rep 14(10):2362-74 |
| abstractText | 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. Here, we present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via alpha7-nicotinic acetylcholine receptors (alpha7-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 alpha7-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 alpha7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity. |
