Issue |
Med Sci (Paris)
Volume 21, Number 1, Janvier 2005
|
|
---|---|---|
Page(s) | 61 - 65 | |
Section | M/S Revues | |
DOI | https://doi.org/10.1051/medsci/200521161 | |
Published online | 15 January 2005 |
Les peptides natriurétiques : Une nouvelle voie de régulation de la lipolyse chez l’homme
Natriuretic peptides : a new lipolytic pathway in human fat cells
Unité de recherches sur les obésités, Inserm U.586, Institut Louis Bugnard, CHU de Toulouse, TSA50032, 31059 Toulouse Cedex 9, France et Université Paul Sabatier, 31062 Toulouse, France
*
max.lafontan@toulouse.inserm.fr
La mobilisation des réserves lipidiques, stockées sous forme de triglycérides dans le tissue adipeux, relève de l’activation de la lipolyse dans l’adipocyte. Les travaux des 30 dernières années ont établi le rôle essentiel joué par la voie de l’AMP cyclique et la lipase hormono-sensible dans le contrôle de la lipolyse. Les catécholamines et l’insuline sont les agents hormonaux essentiels impliqués dans le contrôle de ce processus dans l’adipocyte humain. Nous rapportons la découverte d’un nouveau mécanisme de contrôle de la lipolyse qui implique les peptides natriurétiques d’origine cardiaque et la voie du GMP cyclique. Ces peptides, qui participent à la gestion de l’homéostasie de l’eau et du sel, agissent également sur l’adipocyte. Ils sont doués de propriétés lipolytiques et leur mécanisme d’action a été établi. De plus, nous montrons leur implication dans le contrôle physiologique de la mobilisation des lipides chez l’homme pendant la pratique d’une activité physique.
Abstract
Human fat cell lipolysis was considered until recently to be an exclusive cAMP/protein-kinase A (PKA)-regulated metabolic pathway under the control of catecholamines and insulin. Moreover, exercise-induced lipid mobilization in humans was considered to mainly depend on catecholamine action and interplay between fat cell β- and α2-adrenergic receptors controlling adenylyl cyclase activity and cAMP production. We have recently demonstrated that natriuretic peptides stimulate lipolysis and contribute to the regulation of lipid mobilization in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) stimulate lipolysis in human isolated fat cells. Activation of the adipocyte plasma membrane type A guanylyl cyclase receptor (NPR-A), increase in intracellular guanosine 3’,5’-cyclic monophosphate (cyclic GMP) levels and activation of hormone-sensitive lipase mediate the action of ANP. ANP does not modulate cAMP production and PKA activity. Increment of cGMP induces the phosphorylation of hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I (cGK-I). Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans. Physiological relevance of the ANP-dependent pathway was demonstrated in young subjects performing physical exercise. ANP plays a role in conjunction with catecholamines in the control of exercise-induced lipid mobilization. This pathway becomes of major importance when subjects are submitted to chronic treatment with a β-blocker. Oral β-adrenoceptor blockade suppresses the β-adrenergic component of catecholamine action in fat cells and potentiates exercise-induced ANP release by the heart. These findings may have several implications whenever natriuretic peptide secretion is altered such as in subjects with left ventricular dysfunction, congestive heart failure and obesity.
© 2005 médecine/sciences - Inserm / SRMS
Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.
Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.
Initial download of the metrics may take a while.