Vagus nerve mediated liver-brain axis is a major regulator of the metabolic landscape in the liver

Brito, C. F.; Fonseca, R. C.; Rodrigues-Ribeiro, L.; Vaz, B. F.; Tofani, G. S.; Diniz, A. B.; Fernandes, P.; Nunes, N. A.; Pessoa, R. M.; Oliveira, A. C.; Cardoso, V. N.; Fernandes, S. O.; Oliveira, M. P.; Alvarez-Leite, J.; Menezes, G. B.; Ferreira, A. V.; Gorshkov, V.; Kjeldsen, F.; Verano-Braga, T.; Oliveira, A. G.

doi:10.1101/2023.11.16.567412

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bioRxiv · 10.1101/2023.11.16.567412

Vagus nerve mediated liver-brain axis is a major regulator of the metabolic landscape in the liver

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Abstract

BackgroundThe liver serves as a major energetic reservoir for other tissues and its metabolic function is controlled by humoral and neural factors. The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood. MethodsHerein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism. ResultsVagus nerve shapes the metabolic framework of the liver, as surgical ablation (vagotomy; VNX) of this circuitry led to a significant alteration of the hepatic proteome landscape. Differential protein expression and pathway enrichment analyses showed that glycolytic and fatty acid biosynthesis were increased following VNX, whereas {beta}-oxidation was decreased. This metabolic shift facilitated lipid accumulation in hepatocytes. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. ConclusionsThis study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape. HighlightsO_LIVagus nerve is a novel regulator of the hepatic metabolic landscape. C_LIO_LIAblation of vagus nerve neural circuit by vagotomy resulted in a metabolic shift towards glycolysis and fatty acid biosynthesis. C_LIO_LILipid accumulation was increased in vagotomized mice fed with a standard diet. C_LIO_LILiver steatosis was increased following dietary challenges with high-carbohydrate or high-fat diets. C_LIO_LIVagus nerve can be a promising new target for NAFLD treatment. C_LI

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Brito, C. F., Fonseca, R. C., Rodrigues-Ribeiro, L., Vaz, B. F., Tofani, G. S., Diniz, A. B., Fernandes, P., Nunes, N. A., Pessoa, R. M., Oliveira, A. C., Cardoso, V. N., Fernandes, S. O., Oliveira, M. P., Alvarez-Leite, J., Menezes, G. B., Ferreira, A. V., Gorshkov, V., Kjeldsen, F., Verano-Braga, T., Oliveira, A. G.. 2023-11-17. Vagus nerve mediated liver-brain axis is a major regulator of the metabolic landscape in the liver. https://doi.org/10.1101/2023.11.16.567412

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