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Plasma Levels and Adipose Tissue Messenger Ribonucleic Acid Expression of Retinol-Binding Protein 4 Are Reduced during Calorie Restriction in Obese Subjects but Are Not Related to Diet-Induced Changes in Insulin Sensitivity

Institut National de la Santé et de la Recherche Médicale (M.V., E.K., M.K., C.V., C.M., J.P., F.C., N.V., B.R., M.B., J.He., V.S., D.L.), Franco-Czech Laboratory for Clinical Research on Obesity, Prague, CZ-10100 Czech Republic; Department of Sports Medicine (M.V., E.K., M.K., J.P., B.R., M.B., J.He., V.S.), and Division of Cell and Molecular Biology (M.K.), 3rd Faculty of Medicine, Charles University, Prague, CZ-100 00 Czech Republic; Institut National de la Santé et de la Recherche Médicale (M.V., E.K., C.V., C.M., F.C., N.V., D.L.), U858, Obesity Research Laboratory, Toulouse, F-31432 France; Institute for Mother and Child Care (J.Ha.), Prague, Czech Republic; Paul Sabatier University (E.K., C.V., C.M., F.C., N.V., D.L.), Louis Bugnard Institute, IFR31, Toulouse, F-31432 France; and Centre Hospitalier Universitaire de Toulouse (D.L.), Biochemistry Laboratory, Biology Institute of Purpan, Toulouse, F-31059 France

Address all correspondence and requests for reprints to: Dominique Langin, Institut National de la Santé et de la Recherche Médicale Université Paul Sabatier U858, IFR31, BP 84225, 31432 Toulouse Cedex 4, France. E-mail: langin{at}toulouse.inserm.fr.

Context: Retinol-binding protein 4 (RBP4) may play a role in the development of insulin resistance.

Objective: We investigated whether RBP4 adipose tissue mRNA expression and plasma level are related to insulin sensitivity during a diet-induced weight loss.

Design, Setting, Patients, and Intervention: Obese women followed a dietary intervention composed of a 4-wk very low-calorie diet (VLCD), a 2-month low-calorie diet, and 3–4 months of a weight maintenance (WM) phase.

Main Outcome Measures: Clinical investigation was performed before and at the end of each phase. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp. Adipose tissue mRNA and plasma levels of RBP4 were determined using reverse transcription-quantitative PCR and ELISA, respectively.

Results: Weight and fat mass decreased during VLCD and were stabilized during WM. Glucose disposal rate increased during VLCD and remained elevated thereafter. Plasma levels of RBP4 decreased after VLCD and, although increasing at subsequent phases, remained lower than prediet values. Adipose tissue mRNA levels were diminished after VLCD, and increased during low-calorie diet and WM to reach basal values. Basal RBP4 levels or diet-induced variations of RBP4 were not different in lean women and two groups of obese women with high- and low-insulin sensitivity.

Conclusions: Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. The study does not bring evidence for a role for RBP4 in the regulation of diet-induced changes in insulin sensitivity.

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