β-Carotene and its cleavage enzyme β-carotene-15,15'-oxygenase (CMOI) affect retinoid metabolism in developing tissues

FASEB J. 2011 May;25(5):1641-52. doi: 10.1096/fj.10-175448. Epub 2011 Feb 1.

Abstract

The mammalian embryo relies on maternal circulating retinoids (vitamin A derivatives) for development. β-Carotene is the major human dietary provitamin A. β-Carotene-15,15'-oxygenase (CMOI) has been proposed as the main enzyme generating retinoid from β-carotene in vivo. CMOI is expressed in embryonic tissues, suggesting that β-carotene provides retinoids locally during development. We performed loss of CMOI function studies in mice lacking retinol-binding protein (RBP), an established model of embryonic vitamin A deficiency (VAD). We show that, unexpectedly, lack of CMOI in the developing tissues further exacerbates the severity of VAD and thus the embryonic malformations of RBP(-/-) mice. Since β-carotene was not present in any of the mouse diets, we unveiled a novel action of CMOI independent from its β-carotene cleavage activity. We also show for the first time that CMOI exerts an additional function on retinoid metabolism by influencing retinyl ester formation via modulation of lecithin:retinol acyltransferase (LRAT) activity, at least in developing tissues. Finally, we demonstrate unequivocally that β-carotene can serve as an alternative vitamin A source for the in situ synthesis of retinoids in developing tissues by the action of CMOI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acyltransferases / metabolism
  • Animals
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Embryo, Mammalian / enzymology
  • Embryo, Mammalian / metabolism*
  • Female
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Retinoids / metabolism*
  • Retinol-Binding Proteins / genetics
  • Retinol-Binding Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tretinoin / metabolism
  • Vitamin A / metabolism
  • beta Carotene / metabolism*
  • beta-Carotene 15,15'-Monooxygenase / genetics
  • beta-Carotene 15,15'-Monooxygenase / metabolism*

Substances

  • Retinoids
  • Retinol-Binding Proteins
  • beta Carotene
  • Vitamin A
  • Tretinoin
  • beta-Carotene 15,15'-Monooxygenase
  • Acyltransferases
  • lecithin-retinol acyltransferase