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J. Nutr. First published December 23, 2009; doi:10.3945/jn.109.115147
 Journal of Nutrition, doi:10.3945/jn.109.115147
Vol. 140, No. 2, 311-316, February 2010
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© 2010 American Society for Nutrition

Nutrition and Disease

All-trans Retinoic Acid Lowers Serum Retinol-Binding Protein 4 Concentrations and Increases Insulin Sensitivity in Diabetic Mice1–3,

Daniel-Constantin Manolescu, Aurelia Sima and Pangala V. Bhat*

Laboratory of Nutrition and Cancer, Centre de recherché du Centre hospitalier de l'Université de Montréal-Hôtel-Dieu; Department of Medicine, Université de Montréal, Montreal, H2W 1T7, Canada

Recent investigations have demonstrated that elevated serum retinol-binding protein 4 (RBP4) secreted from adipose tissue plays a role in the development of systemic insulin resistance, and lowering RBP4 improves insulin sensitivity. These observations provide a rationale for the development of new antidiabetic agents aimed at reducing serum RBP4 concentrations. In this study, we sought to determine whether retinoic acid (RA) administration decreases serum RBP4 and suppresses insulin resistance in diabetic ob/ob mice. All-trans RA [100 µg/(mouse•d) in corn oil] was administered by stomach intubation to a group of ob/ob mice, with the control group receiving the vehicle for 16 d. Body weight and food intake were monitored. Glucose and insulin tolerance tests were performed. We quantified serum RBP4 and retinol by Western blotting and HPLC, respectively. RA treatment reduced body weight (P < 0.05), basal serum glucose (P < 0.001), serum retinol (P < 0.01), and RBP4 (P < 0.05). It improved insulin sensitivity and decreased the retinol:RBP4 ratio (P < 0.05). These studies suggest that RA is an effective antidiabetic agent that could be considered in the treatment of type 2 diabetes.

* To whom correspondence should be addressed. E-mail: pangala.v.bhat{at}umontreal.ca.

Manuscript received 26 August 2009. Initial review completed 4 October 2009. Revision accepted 1 December 2009.

Published online 23 December 2009.