To the Editor: Adipose tissue has an important endocrine function, producing a variety of bioactive proteins that may regulate energy metabolism and insulin sensitivity. It releases a variety of the so-called adipokines, including retinol binding protein 4 (RBP4), which has recently been described as a link between obesity and insulin resistance [1] in addition to its primary function as a specific carrier of vitamin A in the blood. In diabetic patients, RBP4 levels are correlated with the degree of insulin resistance [2] and with components of the metabolic syndrome, such as BMI, triacylglycerol levels and blood pressure. Conversely, exercise and weight loss have been reported to decrease both RBP4 levels and insulin resistance [2]. However, the link between RBP4 and obesity is controversial, as several other studies have not found RBP4 to be associated with overall obesity or insulin resistance [3, 4]. In addition, one study reported no difference in circulating RBP4 levels between lean and obese women [5], a finding confirmed very recently [6]. Furthermore, subcutaneous adipose tissue from obese women was characterised by lower RBP4 production compared with lean controls [5]. In these adipose tissue biopsies, GLUT4 levels correlated with RBP4 concentration, making it more likely that RBP4 levels positively correlate with insulin sensitivity in this study. Data on RBP4 production and regulation in human adipocytes are not available, and so the contribution of adipocytes to adipose tissue RBP4 output is difficult to evaluate. In the present study, primary human preadipocytes were isolated from mammary adipose tissue samples of normal or moderately overweight women (age 40.5±3.8 years, BMI 24.2±2.7 kg/m, n=4 in each group) undergoing surgical mammary reduction. All subjects were healthy, free of medication and had no evidence of diabetes according to routine laboratory tests. Adipose tissue samples were dissected from other tissues, pieces of ∼10 mg in weight were minced and preadipocytes were isolated by collagenase digestion as previously described [7]. Isolated preadipocytes were seeded in DMEM/Hams F12 medium supplemented with 10% fetal calf serum and kept in culture overnight. Adipocytes were differentiated over 15 days in a differentiation medium (DMEM/F12, 33 μmol/l biotin, 17 μmol/l D-pantothenic acid, 66 nmol/l insulin, 1 nmol/l triiodo-L-thyronine, 100 nmol/l cortisol, 10 μg/ml apotransferrin, 50 μg/μl gentamicin, 15 mmol/l HEPES, 14 mmol/l NaHCO3, pH 7.4). After 15 days of culture, 60–80% of cells were differentiated as defined by cytoplasm filled with small or large lipid droplets. Differentiated adipocytes were treated with recombinant human adiponectin (Tebu, Offenbach, Germany), troglitazone and recombiDiabetologia (2007) 50:2221–2223 DOI 10.1007/s00125-007-0764-3
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