RESUMEN
OBJECTIVE: Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients. METHODS: Venous mid-regional pro-ANP concentration was assessed at rest and after incremental exhaustive exercise testing before and after weight reduction. We also measured natriuretic peptide receptor A and C mRNA expression in subcutaneous adipose tissue to gauge both ANP responsiveness and clearance mechanisms. RESULTS: The average weight reduction of 9.1â±â3.8â kg was associated with reductions in visceral and subcutaneous abdominal fat mass, liver fat content, insulin resistance, and ambulatory blood pressure. However, mid-regional pro-ANP plasma concentrations were unchanged with weight loss (51â±â24 vs. 53â±â24 âpmol/l). Exercise elicited similar acute mid-regional pro-ANP increases before and after weight loss. Adipose tissue natriuretic peptide receptor type A mRNA expression remained unchanged, whereas natriuretic peptide receptor type C mRNA decreased with weight loss. CONCLUSIONS: We conclude that physical exercise acutely increases ANP release in obese patients, whereas modest diet-induced weight loss primarily affects ANP clearance mechanisms. Interventions combining weight loss and regular physical exercise may be particularly efficacious in reversing obesity-associated relative natriuretic peptide deficiency.
Asunto(s)
Factor Natriurético Atrial/metabolismo , Ejercicio Físico/fisiología , Obesidad/terapia , Pérdida de Peso/fisiología , Programas de Reducción de Peso , Tejido Adiposo/metabolismo , Adulto , Factor Natriurético Atrial/sangre , Monitoreo Ambulatorio de la Presión Arterial , Dieta Reductora , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad/sangre , Receptores del Factor Natriurético Atrial/biosíntesis , Receptores del Factor Natriurético Atrial/genética , DescansoRESUMEN
OBJECTIVE: Endocannabinoid system (ECS) activation promotes obesity-associated metabolic disease. Increased dietary fat intake increases blood endocannabinoids and alters adipose and skeletal muscle ECS gene expression in human. METHODS: Two weeks isocaloric low- (LFD) and high-fat diets (HFD) in obese (n = 12) and normal-weight (n = 17) subjects in a randomized cross-over study were compared. Blood endocannabinoids were measured in the fasting condition and after food intake using mass spectrometry. Adipose and skeletal muscle gene expression was determined using real-time RT-PCR. RESULTS: Baseline fasting plasma endocannabinoids were similar with both diets. Anandamide decreased similarly with high- or low-fat test meals in both groups. Baseline arachidonoylglycerol plasma concentrations were similar between groups and diets, and unresponsive to eating. In subcutaneous adipose tissue, DAGL-α mRNA was upregulated and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mRNAs were down-regulated in obese subjects, but the diets had no influence. In contrast, the HFD produced pronounced reductions in skeletal muscle CB1-R and MAGL mRNA expression, whereas obesity did not affect muscular gene expression. CONCLUSIONS: Weight-neutral changes in dietary fat intake cannot explain excessive endocannabinoid availability in human obesity. Obesity and dietary fat intake affect ECS gene expression in a tissue-specific manner.