Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women

Abstract

OBJECTIVE: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.

Competitive binding of musclin to natriuretic peptide receptor 3 with atrial natriuretic peptide

“…However, other studies suggested that NPR3 gene expression is decreased markedly by fasting (Sarzani et al 1995), and therefore, the tissue bioactivity of ANP might be promoted in fasting conditions. Increased ANP bioactivity related to NPR3 expression could be related to increased natriuresis, diuresis, hypotension, and lipolysis under low-calorific diets or fasting conditions (Sigler 1975, Sarzani et al 1995, Dessì-Fulgheri et al 1999, Sengenes et al 2002. ANP also has the switching role in glycolysis from anaerobic to aerobic metabolism (Birkenfeld et al 2005).…”

The Influence of Diabetes on the Relationship between N-terminal Pro-B-type Natriuretic Peptide and Body Mass Index

“…One explanation is that the natriuretic system and adiposity are closely linked, bidirectionally. 29 Lipolysis is mediated by catecholamines (stimulation of lipolysis) and insulin (inhibition of lipolysis). Natriuretic peptides have been shown to be important stimuli for lipolysis in humans and are similar in potency to catecholamines, and their effect is independent of both catecholamines and an insulin pathway.…”

Involvement of a cGMP-dependent Pathway in the Natriuretic Peptide-mediated Hormone-sensitive Lipase Phosphorylation in Human Adipocytes

“…In previous studies, we have demonstrated that ANP and brain NP, but not C-type NP, are potent stimulators of human fat cell lipolysis (1, 2). Clinical studies have validated their action in vivo (13,14). However, the intracellular pathway involved in the NP-stimulated lipolytic effect still remained to be characterized.…”