title: Central orchestration of peripheral nutrient partitioning and substrate utilization: implications for the metabolic syndrome.
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.
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France.
authors: R G P
authors: RG
authors: Denis
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France.
authors: A
authors: A
authors: Joly-Amado
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France.
authors: C
authors: C
authors: Cansell
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France; Centre national de la recherche scientifique-CNRS, EAC 4413, 75205 Paris, France.
authors: J
authors: J
authors: Castel
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France; Centre national de la recherche scientifique-CNRS, EAC 4413, 75205 Paris, France.
authors: S
authors: S
authors: Martinez
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France; Centre national de la recherche scientifique-CNRS, EAC 4413, 75205 Paris, France.
authors: A S
authors: AS
authors: Delbes
authors: Unité « biologie fonctionnelle et adaptative » (BFA), université Paris Diderot-Paris 7, CNRS EAC 4413, 4, rue Marie-Andrée-Lagroua-Weill-Hallé, bâtiment Buffon, case courrier 7126, 75205 Paris cedex 13, France; Centre national de la recherche scientifique-CNRS, EAC 4413, 75205 Paris, France. Electronic address: serge.luquet@univ-paris-diderot.fr.
authors: S
authors: S
authors: Luquet
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D002149:Energy Intake; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D015430:Weight Gain; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin
keywords: Agouti-related peptide; Diabetes; Hypothalamus; Nutrient partitioning; Obesity