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Studies of adipose tissue vitamin A storage and metabolism in mutant mice
Author(s) -
Wongsiriroj Nuttaporn,
Palczewski Krzysztof,
Blaner William S.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a997
Subject(s) - adipose tissue , endocrinology , medicine , vitamin , acyltransferase , white adipose tissue , retinol , retinyl palmitate , biology , chemistry , enzyme , biochemistry
Work by Yang et al. ( Nature 2005 436 : 356 – 362 ) indicates that retinol‐binding protein (RBP) synthesized in adipose tissue may be an adipokine acting in the causation of diabetes. We demonstrated that adipose tissue vitamin A storage and metabolism involves different enzymes and processes than in the liver, the major site of vitamin A storage in the body (O'Byrne et al. J. Biol. Chem. 2005 280:35647‐35657). Using mutant mice lacking lecithin:retinol acyltransferase (LRAT‐/‐), RBP (RBP‐/‐) and LRAT−/−/RBP−/ − double knockout mice, we carried out studies of adipose vitamin A storage and metabolism to define the enzymes and processes needed for this. LRAT−/ − mice show elevated (by 2‐ to 3‐fold) retinyl ester levels in adipose tissue but totally lack any retinyl esters in liver, lung and kidney. Gavage studies of wild type, LRAT−/ − and RBP−/ − mice suggest that RBP contributes a significant proportion of the vitamin A stored in adipose. This notion is supported by comparison of LRAT−/ − mice with LRAT−/ −/RBP−/ − mice. The absence of RBP in double knockouts greatly diminishes (by approximately 3‐fold) the amount of postprandial vitamin A that is accumulated by adipose tissue. This suggests that newly absorbed dietary vitamin A passes initially through the liver before transfer via RBP to adipose stores. Finally, our in vitro data suggest that diacylglycerol acyltransferase 1 (DGAT1) can act as an acyl‐CoA:retinol acyltransferase (ARAT) in physiologic situations. Using LRAT−/ − and LRAT−/ −/DGAT1−/ − mice we are assessing the physiologic significance of DGAT1 as an ARAT in adipose tissue. (Supported by NIH grant R01 DK068437)