Cited by 392Pancreatic function and diabetesRegulation of Appetite and ObesityMetabolism, Diabetes, and Cancer

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A brain-liver circuit regulates glucose homeostasis

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Pocai, Alessandro, Obici, Silvana, Schwartz, Gary J., Rossetti, Luciano·2005·Cell Metabolism

DOI 10.1016/j.cmet.2004.11.001

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Abstract

Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

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Self-citation
Molecular signaling networks that connect tissue dysfunction to systemic insulin resistance
Mir, R., Algehainy, N. A., Jalal, M. M., Altayar, M. A., Almotairi, R., Tayeb, F. J., Bedaiwi, R. I., Altemani, F. H., Almasoudi, K. S., Albalawi, I. A., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1952238

Authors: Pocai, A., Obici, S., Schwartz, G. J., & Rossetti, L.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Rossetti, Luciano
ORCID: Pocai, Alessandro
Schwartz, Gary J.
Rossetti, Luciano
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2005-01
Volume: 1
Issue: 1
Pages: 53-61
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2004.11.001
OpenAlex: W2054716401
Cited by: 392
References: 43
Citations by year: 2026: 5 · 2025: 10 · 2024: 20 · 2023: 9 · 2022: 15 · 2021: 14 · 2020: 19 · 2019: 16 · 2018: 10 · 2017: 22 · 2016: 19 · 2015: 17 · 2014: 15 · 2013: 21 · 2012: 26
FWCI: 27.68
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3119 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK-47208, R01DK047208, DK20541, DK-45024)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: glucose homeostasis, fasting hyperglycemia, liver gluconeogenesis, glucose production, nucleus tractus solitarius, dorsal motor nucleus of the vagus, brainstem neurons, ATP-sensitive potassium channels, fat oxidation, diabetes mellitus
MeSH terms: Adenosine Triphosphate, Animals, Brain, Central Nervous System, Glucose, Homeostasis, Hyperglycemia, Kinetics, Liver, Male, Models, Biological, Neurons, Oxygen, Pancreas, Phosphoric Monoester Hydrolases, Potassium, Vagus Nerve, Potassium Channels, Glucose Clamp Technique, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Lipid Metabolism, Rats

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A brain-liver circuit regulates glucose homeostasis

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