Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice
Year: 2025
Type: article
Abstract: The visceral organ-brain axis, mediated by vagal sensory neurons, is essential for maintaining various physiological functions. Here, we investigate the impact of liver-projecting vagal sensory neurons on energy balance, hepatic steatosis, and anxiety-like behavior in mice under obesogenic conditions. A small subset of vagal sensory neurons in both the left and right ganglia innervate the liver and project centrally to the nucleus of the tractus solitarius, area postrema, and dorsal motor nucleus of the vagus, and peripherally to the periportal areas in the liver. Surprisingly, the loss of liver-projecting vagal sensory neurons via caspase-induced selective destruction of advillin-positive neurons prevents diet-induced obesity, and these outcomes are associated with increased energy expenditure. Although males and females exhibit improved glucose homeostasis following disruption of liver-projecting vagal sensory neurons, only male mice display increased insulin sensitivity. Furthermore, the loss of liver-projecting vagal sensory neurons limits the progression of hepatic steatosis in mice fed a steatogenic diet. Intriguingly, mice lacking liver-innervating vagal sensory neurons also exhibit less anxiety-like behavior compared to control mice. Therefore, modulation of the liver-brain axis may aid in designing effective treatments for both psychiatric and metabolic disorders associated with obesity and MAFLD.
Source: Nature Communications
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, NIH Blueprint for Neuroscience Research, National Center for Complementary and Integrative Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1141970910, G1205869946, G1513221621, Role of hypothalamic MAGEL2 in motivation, G2184084671, G464855746, Energy Homeostasis: GABAergic and Non-GABAergic POMC neurons, G5256832686, G5387367091, G5753762322, G6128132460, Energy Homeostasis: GABAergic and Non-GABAergic POMC neurons, Diabetes Research and Training Center, G88737082, G9000065207, Role of cholinergic innervation of the liver, Functional identification of vagal sensory neurons innervating the liver, SUPPORT FOR THE ROSE F KENNEDY IDDRC P50, NYR-Diabetes Research Center (NYR-DRC), Discordant transcriptional regulation of gluconeogenic and lipogenic gene expression, G999091674
OpenAlex ID: W4406798552