Apo-14´-Carotenoic Acid Is a Novel Endogenous and Bioactive Apo-Carotenoid

Nutrients. 2019 Sep 4;11(9):2084. doi: 10.3390/nu11092084.


Carotenoids can be metabolized to various apo-carotenoids and retinoids. Apo-15´-carotenoic acid (retinoic acid, RA) is a potent activator of the retinoic acid receptor (RAR) in its all-trans- (ATRA) and 9-cis- (9CRA) forms. In this study we show firstly, that apo-14´-carotenoic acid (A14CA), besides retinoic acids, is present endogenously and with increased levels in the human organism after carrot juice supplementation rich in β-carotene. All-trans-A14C (ATA14CA) is just a moderate activator of RAR-transactivation in reporter cell lines but can potently activate retinoic acid response element (RARE)-mediated signalling in DR5/RARE-reporter mice and potently increase retinoid-reporter target gene expression in ATA14CA-supplemented mice and treated MM6 cells. Further metabolism to all-trans-13,14-dihydroretinoic acid (ATDHRA) may be the key for its potent effects on retinoid target gene activation in ATA14CA-treated MM6 cells and in liver of supplemented mice. We conclude that besides RAs, there are alternative ways to activate RAR-response pathways in the mammalian organism. ATA14CA alone and in combination with its metabolite ATDHRA may be an alternative pathway for potent RAR-mediated signalling.

Keywords: apo-carotenoids; carotene; retinoic acid; vitamin A.

MeSH terms

  • Adult
  • Animals
  • Carotenoids / administration & dosage
  • Carotenoids / chemistry
  • Carotenoids / metabolism
  • Carotenoids / pharmacology*
  • Cell Line
  • Daucus carota / chemistry
  • Fruit and Vegetable Juices / analysis
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Mice
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism


  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • apo-14'-carotenoic acid
  • Carotenoids