The lipid-mobilizing effect of atrial natriuretic peptide is unrelated to sympathetic nervous system activation or obesity in young men (original) (raw)
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Atrial natriuretic peptide contributes to the physiological control of lipid mobilization in humans
Faseb Journal, 2004
In humans, lipid mobilization is considered to depend mainly on sympathetic nervous system activation and catecholamine action. A contribution of ANP was hypothesized because we have previously shown that atrial natriuretic peptide (ANP) is a lipolytic agent on isolated human fat cells. Control of lipid-mobilizing mechanisms was investigated using in situ microdialysis in subcutaneous adipose tissue (SCAT) in healthy young men during two successive exercise bouts performed at 35% and 60% peak oxygen consumption (VO 2 max) after placebo or acute oral tertatolol (nonselective β-antagonist) treatment. In placebo-treated subjects, infusion of propranolol in the probe (100 µmol/l) only partially reduced (40%) the increment in extracellular glycerol concentration (EGC) promoted by exercise. Moreover, oral β-adrenergic receptor blockade did not prevent exercise-induced lipid mobilization in SCAT while exerting fat cell βadrenergic receptor blockade. Exercise-induced increase in plasma ANP was potently amplified by oral tertatolol. A positive correlation was found between EGC and plasma ANP levels but also between extracellular cGMP (i.e., index of ANP-mediated lipolysis) and EGC. Thus, we demonstrate that exercise-induced lipid mobilization resistant to local propranolol and lipidmobilizing action observed under oral β-blockade is related to the action of ANP. Oral βadrenergic receptor blockade, which potentiates exercise-induced ANP release by the heart, may contribute to lipid mobilization in SCAT. The potential relevance of an ANP-related lipidmobilizing pathway is discussed.
International Journal of Obesity, 2002
We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 mg=m 2 min for 60 min). SUBJECTS: Ten obese women from 40.5 AE 3.4 y old were selected for this study. Their body weight was 96.4 AE 5.7 kg and their BMI was 35.3 AE 1.7 kg=m 2 . They received a 2.5 -2.9 MJ=day formula diet for 28 days. DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis. RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80 -100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment. CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol-and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3Ј, 5Ј-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral -blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.
AJP: Endocrinology and Metabolism, 2008
Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol [a β-adrenergic receptor (AR) antagonist]. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (α-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the α2-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the β-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin conc...
Expression and Secretion of the Atrial Natriuretic Peptide in Human Adipose Tissue and Preadipocytes
2007
GARRUTI, GABRIELLA, VITTORIO GIUSTI, JÜ RG NUSSBERGER, CHRISTIAN DARIMONT, CHANTAL VERDUMO, CATHERINE AMSTUTZ, FRANCESCO PUGLISI, FRANCESCO GIORGINO, RICCARDO GIORGINO, AND SUSANNA COTECCHIA. Expression and secretion of the atrial natriuretic peptide in human adipose tissue and preadipocytes. Obesity. 2007;15: 2181-2189.
Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise
AJP: Endocrinology and Metabolism, 2006
Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid mobilization is increased during repeated bouts of exercise, but the underlying mechanisms involved in this process have not yet been delineated. The relative involvement of catecholamine- and ANP-dependent pathways in the control of lipid mobilization during repeated bouts of exercise was thus investigated in subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of their maximal oxygen uptake separated by a 60-min rest period. Extracellular glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a control probe perfused with Ringer solution and in two other probes perfused with either Ringer plus phentolamine (α1/2-AR antagonist) or Ringer plus both phentolamine and propranolol (β-AR antagonist). Plasma epinephrine, plasma glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 t...
Natriuretic peptides: a new lipolytic pathway in human adipocytes
Faseb Journal, 2000
Atrial natriuretic peptide (ANP) receptors have been described on rodent adipocytes and expression of their mRNA is found in human adipose tissue. However, no biological effects associated with the stimulation of these receptors have been reported in this tissue. A putative lipolytic effect of natriuretic peptides was investigated in human adipose tissue. On isolated fat cells, ANP and brain natriuretic peptide (BNP) stimulated lipolysis as much as isoproterenol, a nonselective -adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. In situ microdialysis experiments confirmed the potent lipolytic effect of ANP in abdominal s.c. adipose tissue of healthy subjects. A high level of ANP binding sites was identified in human adipocytes. The potency order defined in lipolysis (ANP > BNP > CNP) and the ANP-induced cGMP production sustained the presence of type A natriuretic peptide receptor in human fat cells. Activation or inhibition of cGMP-inhibited phosphodiesterase (PDE-3B) (using insulin and OPC 3911, respectively) did not modify ANP-induced lipolysis whereas the isoproterenol effect was decreased or increased. Moreover, inhibition of adenylyl cyclase activity (using a mixture of ␣ 2 -adrenergic and adenosine A1 agonists receptors) did not change ANP-but suppressed isoproterenol-induced lipolysis. The noninvolvement of the PDE-3B was finally confirmed by measuring its activity under ANP stimulation. Thus, we demonstrate that natriuretic peptides are a new pathway controlling human adipose tissue lipolysis operating via a cGMP-dependent pathway that does not involve PDE-3B inhibition and cAMP production.-Sengenès, C., Berlan, M., De Glisezinski, I., Lafontan, M., Galitzky, J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J. 14, 1345-1351 (2000) Key Words: human fat cells ⅐ ANP ⅐ BNP ⅐ lipolysis ⅐ microdialysis 1345 0892-6638/00/0014-1345/$02.25 © FASEB