Retinol-binding protein 2 (RBP2) binds monoacylglycerols and modulates gut endocrine signaling and body weight

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Abstract
Expressed in the small intestine, retinol-binding protein 2 (RBP2) facilitates dietary retinoid absorption. Rbp2-deficient (Rbp2−/−) mice fed a chow diet exhibit by 6-7 months-of-age higher body weights, impaired glucose metabolism, and greater hepatic triglyceride levels compared to controls. These phenotypes are also observed when young Rbp2−/− mice are fed a high fat diet. Retinoids do not account for the phenotypes. Rather, RBP2 is a previously unidentified monoacylglycerol (MAG)-binding protein, interacting with the endocannabinoid 2-arachidonoylglycerol (2-AG) and other MAGs with affinities comparable to retinol. X-ray crystallographic studies show that MAGs bind in the retinol binding pocket. When challenged with an oil gavage, Rbp2−/− mice show elevated mucosal levels of 2-MAGs. This is accompanied by significantly elevated blood levels of the gut hormone GIP (glucose-dependent insulinotropic polypeptide). Thus, RBP2, in addition to facilitating dietary retinoid absorption, modulates MAG metabolism and likely signaling, playing a heretofore unknown role in systemic energy balance.
Funding Information
  • National Institutes of Health (R01 DK068437)
  • National Institutes of Health (R01 DK101251)
  • National Institutes of Health (R01 EY023948)
  • National Institutes of Health (P30 DK026687)
  • National Institutes of Health (R01 DK052431)
  • National Institutes of Health (R01 DK038389)
  • Université de Strasbourg (Institute of Advanced Study)
  • NIDDK (R01 DK122071)
  • National Institutes of Health (T32 DK007647)
  • National Institutes of Health (T32 DK007328)

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