Lipolytic catecholamine resistance linked to α₂-adrenoceptor sensitivity—a metabolic predictor of weight loss in obese subjects

Abstract

OBJECTIVE: The weight loss achieved during treatment with very-low-calorie diets (VLCD) varies between individuals. The aim of this study was to investigate whether interindividual variations in catecholamine-induced lipolysis are of importance for the rate of weight loss during VLCD. DESIGN: Prospective study. SUBJECTS: Twenty-eight obese, but otherwise healthy and drug-free women aged 20–57 y with BMI 33.3–47.5 kg/m² were investigated before entering a four week weight reduction program with a calorie-restricted diet. MEASUREMENTS: A subcutaneous adipose tissue biopsy was obtained from the abdominal area. Isolated fat cells were prepared and incubated in vitro with agents acting on lipolysis at defined steps in the lipolytic cascade. Glycerol release was measured and used as a lipolytic index. Following the biopsy, the subjects underwent a four week VLCD treatment. RESULTS: The decrease in body weight in the whole group ranged between 4.8 and 13.5 kg. Dietary compliance was ascertained by daily measurements of urine-ketones and regular interviews and was satisfactory in all subjects throughout the study. Based on percent body weight reduction, the material was divided into two equally sized groups, classified as rapid or slow weight losers. The rapid weight losers were 10-fold more sensitive to the lipolytic effect of noradrenaline (P=0.04) and 10-fold less sensitive (P=0.002) to the antilipolytic effect induced by the α₂-adrenoceptor agonist clonidine than the slow weight losers. In the whole material, weight loss was significantly correlated (adjusted r²=0.25) with α₂-adrenoceptor sensitivity. CONCLUSION: Rapid weight loss during VLDC is associated with increased adipocyte lipolytic sensitivity to catecholamines due to decreased α₂-adrenoceptor sensitivity, which in turn may promote lipid mobilization. It appears that variations in α₂-adrenoceptor sensitivity in adipocytes may be predictive of weight loss during VLCD.