A brain-liver circuit regulates glucose homeostasis

Alessandro Pocai, Silvana Obici, Gary J. Schwartz, Luciano Rossetti

Research output: Contribution to journalArticle

262 Citations (Scopus)

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 (KATP) 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 KATP 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.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalCell Metabolism
Volume1
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Homeostasis
Glucose
Liver
Brain
Food
Hyperglycemia
Brain Stem
Neurons
Solitary Nucleus
Vagus Nerve
Gluconeogenesis
Potassium Channels
Lipid Metabolism
Fasting
Diabetes Mellitus
Adenosine Triphosphate
Fats
Lipids
Enzymes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

A brain-liver circuit regulates glucose homeostasis. / Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J.; Rossetti, Luciano.

In: Cell Metabolism, Vol. 1, No. 1, 01.2005, p. 53-61.

Research output: Contribution to journalArticle

Pocai, Alessandro ; Obici, Silvana ; Schwartz, Gary J. ; Rossetti, Luciano. / A brain-liver circuit regulates glucose homeostasis. In: Cell Metabolism. 2005 ; Vol. 1, No. 1. pp. 53-61.
@article{dc94f8e2010d4377b425259e312a8bff,
title = "A brain-liver circuit regulates glucose homeostasis",
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 (KATP) 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 KATP 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.",
author = "Alessandro Pocai and Silvana Obici and Schwartz, {Gary J.} and Luciano Rossetti",
year = "2005",
month = "1",
doi = "10.1016/j.cmet.2004.11.001",
language = "English (US)",
volume = "1",
pages = "53--61",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - A brain-liver circuit regulates glucose homeostasis

AU - Pocai, Alessandro

AU - Obici, Silvana

AU - Schwartz, Gary J.

AU - Rossetti, Luciano

PY - 2005/1

Y1 - 2005/1

N2 - 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 (KATP) 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 KATP 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.

AB - 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 (KATP) 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 KATP 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.

UR - http://www.scopus.com/inward/record.url?scp=16244383657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16244383657&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2004.11.001

DO - 10.1016/j.cmet.2004.11.001

M3 - Article

C2 - 16054044

AN - SCOPUS:16244383657

VL - 1

SP - 53

EP - 61

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -