Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue
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Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue. / Wongsiriroj, Nuttaporn; Jiang, Hongfeng; Piantedosi, Roseann; Yang, Kryscilla Jian Zhang; Kluwe, Johannes; Schwabe, Robert F; Ginsberg, Henry; Goldberg, Ira J; Blaner, William S.
In: J LIPID RES, Vol. 55, No. 1, 01.01.2014, p. 104-114.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue
AU - Wongsiriroj, Nuttaporn
AU - Jiang, Hongfeng
AU - Piantedosi, Roseann
AU - Yang, Kryscilla Jian Zhang
AU - Kluwe, Johannes
AU - Schwabe, Robert F
AU - Ginsberg, Henry
AU - Goldberg, Ira J
AU - Blaner, William S
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Approximately 80-90% of all retinoids in the body are stored as retinyl esters (REs) in the liver. Adipose tissue also contributes significantly to RE storage. The present studies, employing genetic and nutritional interventions, explored factors that are responsible for regulating RE accumulation in the liver and adipose tissue and how these influence levels of retinoic acid (RA) and RA-responsive gene expression. Our data establish that acyl-CoA:retinol acyltransferase (ARAT) activity is not involved in RE synthesis in the liver, even when mice are nutritionally stressed by feeding a 25-fold excess retinol diet or upon ablation of cellular retinol-binding protein type I (CRBPI), which is proposed to limit retinol availability to ARATs. Unlike the liver, where lecithin:retinol acyltransferase (LRAT) is responsible for all RE synthesis, this is not true for adipose tissue where Lrat-deficient mice display significantly elevated RE concentrations. However, when CrbpI is also absent, RE levels resemble wild-type levels, suggesting a role for CrbpI in RE accumulation in adipose tissue. Although expression of several RA-responsive genes is elevated in Lrat-deficient liver, employing a sensitive liquid chromatography tandem mass spectrometry protocol and contrary to what has been assumed for many years, we did not detect elevated concentrations of all-trans-RA. The elevated RA-responsive gene expression was associated with elevated hepatic triglyceride levels and decreased expression of Pparδ and its downstream Pdk4 target, suggesting a role for RA in these processes in vivo.
AB - Approximately 80-90% of all retinoids in the body are stored as retinyl esters (REs) in the liver. Adipose tissue also contributes significantly to RE storage. The present studies, employing genetic and nutritional interventions, explored factors that are responsible for regulating RE accumulation in the liver and adipose tissue and how these influence levels of retinoic acid (RA) and RA-responsive gene expression. Our data establish that acyl-CoA:retinol acyltransferase (ARAT) activity is not involved in RE synthesis in the liver, even when mice are nutritionally stressed by feeding a 25-fold excess retinol diet or upon ablation of cellular retinol-binding protein type I (CRBPI), which is proposed to limit retinol availability to ARATs. Unlike the liver, where lecithin:retinol acyltransferase (LRAT) is responsible for all RE synthesis, this is not true for adipose tissue where Lrat-deficient mice display significantly elevated RE concentrations. However, when CrbpI is also absent, RE levels resemble wild-type levels, suggesting a role for CrbpI in RE accumulation in adipose tissue. Although expression of several RA-responsive genes is elevated in Lrat-deficient liver, employing a sensitive liquid chromatography tandem mass spectrometry protocol and contrary to what has been assumed for many years, we did not detect elevated concentrations of all-trans-RA. The elevated RA-responsive gene expression was associated with elevated hepatic triglyceride levels and decreased expression of Pparδ and its downstream Pdk4 target, suggesting a role for RA in these processes in vivo.
KW - Adipose Tissue, White
KW - Animals
KW - Epididymis
KW - Esterification
KW - Esters
KW - Female
KW - Gene Expression
KW - Gene Expression Regulation
KW - Liver
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - PPAR delta
KW - Phosphatidylcholine-Sterol O-Acyltransferase
KW - Protein-Serine-Threonine Kinases
KW - Retinoids
KW - Retinol O-Fatty-Acyltransferase
KW - Retinol-Binding Proteins, Cellular
KW - Triglycerides
U2 - 10.1194/jlr.M043844
DO - 10.1194/jlr.M043844
M3 - SCORING: Journal article
C2 - 24186946
VL - 55
SP - 104
EP - 114
JO - J LIPID RES
JF - J LIPID RES
SN - 0022-2275
IS - 1
ER -