Vagus Nerve Mediated Liver-Brain-Axis Is a Major Regulator of the Metabolic Landscape in the Liver
The 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. Herein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism in male mice. Liver-brain axis was impaired by vagotomy (VNX) or knocking down of the vesicular acetylcholine transporter (VAChT-KD). Mice were challenged with high carbohydrate or high-fat feeding. The vagus nerve shapes the metabolic framework of the liver, as vagotomy 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 β-oxidation was decreased. These results were corroborated in VAChT-KD mice. This metabolic shift facilitated lipid accumulation in hepatocytes in mice fed with a standard commercial diet. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. This study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape.
Authors
- Amanda Carla Clemente de Oliveira
- Gabriel S. S. Tofani (ORCID: https://orcid.org/0009-0008-5140-1628)
- Simone Odília Antunes Fernandes (ORCID: https://orcid.org/0000-0002-6139-5187)
- Mariana T. Q. de Magalhães (ORCID: https://orcid.org/0000-0003-4912-0233)
- Núbia Alexandre Melo Nunes
- Lucas Rodrigues‐Ribeiro (ORCID: https://orcid.org/0000-0002-4011-637X)
- Ariane Barros Diniz
- Frank Kjeldsen (ORCID: https://orcid.org/0000-0003-0785-2903)
- Alan de Araujo (ORCID: https://orcid.org/0000-0003-2656-4077)
- Vladimir Gorshkov (ORCID: https://orcid.org/0000-0003-0170-5785)
- Paola Fernandes (ORCID: https://orcid.org/0000-0002-2326-1460)
- Maristela O. Poletini (ORCID: https://orcid.org/0000-0003-4917-889X)
- Jacqueline I. Alvarez‐Leite (ORCID: https://orcid.org/0000-0001-6601-9853)
- Adaliene Versiani Matos Ferreira (ORCID: https://orcid.org/0000-0003-2256-8652)
- Roberta Cristelli Fonseca
- Thiago Verano‐Braga (ORCID: https://orcid.org/0000-0002-7083-2588)
- Ana Carolina Silva Batista (ORCID: https://orcid.org/0009-0008-2037-0494)
- Gustavo Batista Menezes (ORCID: https://orcid.org/0000-0001-9887-3616)
- Valbert Nascimento Cardoso (ORCID: https://orcid.org/0000-0001-7597-9602)
- Ivana S. Lula (ORCID: https://orcid.org/0009-0006-3987-5738)
- A. G. de Oliveira (ORCID: https://orcid.org/0000-0002-1744-8229)
- João S. F. Guimarães (ORCID: https://orcid.org/0009-0005-3851-2647)
- Camila F. Brito
- Rafaela Miranda Pessoa
- Bruna Fernandes Vaz
Institutions
- Universidade Federal de Minas Gerais (BR)
- University of Southern Denmark (DK)
- Monell Chemical Senses Center (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-02-28
- DOI
- https://doi.org/10.3390/ijms26052166
- Citations
- 3
- Primary Topic
- Biochemical effects in animals
- Type
- article
- Field-Weighted Citation Impact
- 3.49
Funders
- Pennsylvania Department of Health
- Villum Fonden
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Novo Nordisk
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Syddansk Universitet
- Universidade Federal de Minas Gerais
- Novo Nordisk Fonden
- Servier
- National Institutes of Health
- VILLUM Center for Bioanalytical Sciences
- National Institute of General Medical Sciences