| First Author | Lee SA | Year | 2014 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 307 |
| Issue | 11 | Pages | H1675-84 |
| PubMed ID | 25260612 | Mgi Jnum | J:220799 |
| Mgi Id | MGI:5636144 | Doi | 10.1152/ajpheart.00548.2014 |
| Citation | Lee SA, et al. (2014) Cardiac dysfunction in beta-carotene-15,15'-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism. Am J Physiol Heart Circ Physiol 307(11):H1675-84 |
| abstractText | Dietary carotenoids like beta-carotene are converted within the body either to retinoid, via beta-carotene-15,15'-dioxygenase (BCO1), or to beta-apo-carotenoids, via beta-carotene-9',10'-oxygenase 2. Some beta-apo-carotenoids are potent antagonists of retinoic acid receptor (RAR)-mediated transcriptional regulation, which is required to ensure normal heart development and functions. We established liquid chromatography tandem mass spectrometery methods for measuring concentrations of 10 beta-apo-carotenoids in mouse plasma, liver, and heart and assessed how these are influenced by Bco1 deficiency and beta-carotene intake. Surprisingly, Bco1(-/-) mice had an increase in heart levels of retinol, nonesterified fatty acids, and ceramides and a decrease in heart triglycerides. These lipid changes were accompanied by elevations in levels of genes important to retinoid metabolism, specifically retinol dehydrogenase 10 and retinol-binding protein 4, as well as genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-gamma, lipoprotein lipase, Cd36, stearoyl-CoA desaturase 1, and fatty acid synthase. We also obtained evidence of compromised heart function, as assessed by two-dimensional echocardiography, in Bco1(-/-) mice. However, the total absence of Bco1 did not substantially affect beta-apo-carotenoid concentrations in the heart. beta-Carotene administration to matched Bco1(-/-) and wild-type mice elevated total beta-apo-carotenal levels in the heart, liver, and plasma and total beta-apo-carotenoic acid levels in the liver. Thus, BCO1 modulates heart metabolism and function, possibly by altering levels of cofactors required for the actions of nuclear hormone receptors. |
