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Serum Retinol-Binding Protein-4, Leptin, and Adiponectin Concentrations Are Related to Ectopic Fat Accumulation

Internal Medicine, Section of Nutrition/Metabolism (G.P., G.L., F.R., L.L.), Diagnostic Radiology (F.D.C., A.E., E.B., T.C., A.D.M.) and Nuclear Medicine (P.S.), and Unit of Clinical Spectroscopy (G.P., F.D.C., P.S., A.D.M., L.L.), San Raffaele Scientific Institute; Università Vita e Salute San Raffaele (A.D.M.); and Center for Physical Exercise for Health and Wellness (G.P., L.L.), Faculty of Exercise Sciences, Università degli Studi di Milano, 20132 Milan, Italy

Address all correspondence and requests for reprints to: Gianluca Perseghin, M.D., Faculty of Exercise Sciences, Università degli Studi di Milano and San Raffaele Scientific Institute, Internal Medicine-Section of Nutrition/Metabolism and Unit of Clinical Spectroscopy, via Olgettina 60, 20132 Milan, Italy. E-mail: perseghin.gianluca{at}hsr.it.

Context: Serum retinol-binding protein 4 (RBP-4), leptin, and adiponectin concentrations identify insulin resistance in varied conditions, but their relationships with insulin sensitivity and ectopic fat accumulation are unclear.

Objective: Our objective was to establish how these adipokines are related with intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content.

Design and Setting: We assessed retrospectively serum fasting RBP-4 concentrations in 1) 53 nondiabetic individuals in which insulin sensitivity and IMCL content were assessed by means of the insulin clamp and of ¹H magnetic resonance spectroscopy of the calf muscles, and 2) 140 nondiabetic individuals in which insulin sensitivity and the IHL content were assessed by means of the updated homeostasis model assessment and of ¹H magnetic resonance spectroscopy. In both experiments, serum leptin and adiponectin concentrations were measured.

Results: Fasting serum RBP-4, adiponectin, and leptin were associated with peripheral insulin sensitivity, were abnormal in the first-degree relatives of type 2 diabetic parents, and correlated with the soleus IMCL content and with the IHL content. The association of RBP-4 and adiponectin with insulin sensitivity was age, sex, and body mass index independent, but stepwise regression analysis suggested that RBP-4, but not adiponectin and leptin, was independently associated with insulin sensitivity. Adiponectin was independently associated with the IHL content, RBP-4, and leptin with the soleus IMCL content.

Conclusion: Serum RBP-4 was a robust marker of insulin resistance. Serum RBP-4, leptin, and adiponectin concentrations reflected ectopic fat accumulation in humans.

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