Multiple pathways ensure retinoid delivery to milk: studies in genetically modified mice.
Retinoids are absolutely required for normal growth and development during the postnatal period. We studied the delivery of retinoids to milk, availing of mouse models modified for proteins thought to be essential for this process. Milk retinyl esters were markedly altered in mice lacking the enzyme lecithin:retinol acyltransferase (Lrat(-/-)), indicating that this enzyme is normally responsible for the majority of retinyl esters incorporated into milk and not an acyl-CoA dependent enzyme, as proposed in the literature. Unlike wild-type milk, much of the retinoid in Lrat(-/-) milk is unesterified retinol, not retinyl ester. The composition of the residual retinyl ester present in Lrat(-/-) milk was altered from predominantly retinyl palmitate and stearate to retinyl oleate and medium chain retinyl esters. This was accompanied by increased palmitate and decreased oleate in Lrat(-/-) milk triglycerides. In other studies, we investigated the role of retinol-binding protein in retinoid delivery for milk formation. We found that Rbp(-/-) mice maintain milk retinoid concentrations similar to those in matched wild-type mice. This appears to arise due to greater postprandial delivery of retinoid, a lipoprotein lipase (LPL)-dependent pathway. Importantly, LPL also acts to assure delivery of long-chain fatty acids (LCFA) to milk. The fatty acid transporter CD36 also facilitated LCFA but not retinoid incorporation into milk. Our data show that compensatory pathways for the delivery of retinoids ensure their optimal delivery and that LRAT is the most important enzyme for milk retinyl ester formation.
O'Byrne
Sheila M
SM
Institute of Human Nutrition, Columbia University, New York, NY 10032, USA. so2017@columbia.edu
Kako
Yuko
Y
Deckelbaum
Richard J
RJ
Hansen
Inge H
IH
Palczewski
Krzysztof
K
Goldberg
Ira J
IJ
Blaner
William S
WS
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005260:Female; D007774:Lactation; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008892:Milk / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
D018955:CD36 Antigens; D005227:Fatty Acids; D012176:Retinoids; D012177:Retinol-Binding Proteins; D014280:Triglycerides; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase; D008071:Lipoprotein Lipase