Central orchestration of peripheral nutrient partitioning and substrate utilization: implications for the metabolic syndrome

R G P Denis, A Joly-Amado, C Cansell, J Castel, S Martinez, A S Delbes, S Luquet

Research output: Contribution to journalLiterature reviewpeer-review

23 Citations (Scopus)

Abstract

Energy homoeostasis is maintained through a complex interplay of nutrient intake and energy expenditure. The central nervous system is an essential component of this regulation, as it integrates circulating signals of hunger and satiety to develop adaptive responses at the behavioural and metabolic levels, while the hypothalamus is regarded as a particularly crucial structure in the brain in terms of energy homoeostasis. The arcuate nucleus (ARC) of the hypothalamus contains at least two intermingled neuronal populations: the neurons that produce neuropeptide Y (NPY); and the Agouti-related protein (AgRP) produced by AgRP/NPY neurons situated below the third ventricle in close proximity to proopiomelanocortin (POMC)-producing neurons. POMC neurons exert their catabolic and anorectic actions by releasing α-melanocyte-stimulating hormone (α-MSH), while AgRP neurons oppose this action by exerting tonic GABAergic inhibition of POMC neurons and releasing the melanocortin receptor inverse agonist AgRP. The release of neurotransmitters and neuropeptides by second-order AgRP neurons appears to take place on a multiple time scale, thereby allowing neuromodulation of preganglionic neuronal activity and subsequent control of nutrient partitioning - in other words, the coordinated regulation of conversion, storage and utilization of carbohydrates vs. lipids. This suggests that the function of AgRP neurons extends beyond the strict regulation of feeding to the regulation of efferent organ activity, such that AgRP neurons may now be viewed as an important bridge between central detection of nutrient availability and peripheral nutrient partitioning, thus providing a mechanistic link between obesity and obesity-related disorders.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalDiabetes & Metabolism
Volume40
Issue number3
DOIs
Publication statusPublished - Jun 2014

Bibliographical note

Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Acknowledgments
This work was supported by a young investigator ATIP grant from the National Centre for Scientific Research (Centre national la recherche scientifique, CNRS), an equipment grant from the Île-de-France region, an equipment grant from the Paris Diderot University–Paris 7, a research fellowship from the French Diabetes Society–Lilly and grants from the National Research Agency (Agence nationale de la recherche; ANR-09-BLAN-0267-02 and ANR 11 BSV1 021 01). A.J. received a National merit scholarship from the French Department of National Education and Research, a research grant from the French Diabetes Society (Société francophone du diabète) and a research grant from the SFNEP-ANTADIR. R.D. received a research fellowship from the Région Île-de-France. C.C. received a PhD fellowship from the CNRS and a research grant from the French Diabetes Society–Roche.

Keywords

  • obesity
  • diabetes
  • nutrient partitioning
  • hypothalamus
  • agouti-related peptide

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