Taurine is a liver X receptor-α ligand and activates transcription of key genes in the reverse cholesterol transport without inducing hepatic lipogenesis.
METHODS
Taurine, which is abundant in seafood, has antiatherogenic activities in both animals and humans; however, its molecular target has been elusive. We examined whether taurine could activate liver X receptor-α (LXR-α), a critical transcription factor in the regulation of reverse cholesterol transport in macrophages.


RESULTS
Taurine bound directly to LXR-α in a reporter gene assay, time-resolved fluorescence resonance energy transfer analysis, and limited protease digestion experiment. Macrophage cells incubated with taurine showed reduced cellular cholesterol and induced medium cholesterol in a dose-dependent manner with the induction of ATP-binding cassette transporter A1 and G gene and protein expression. In hepatocytes, taurine significantly induced Insig-2a levels and delayed nuclear translocation of the sterol regulatory element-binding protein 1 (SREBP-1) protein, resulting in a dose-dependent reduction in the cellular lipid levels without inducing the expression of fatty acid synthesis genes.


CONCLUSIONS
Taurine is a direct LXR-α ligand, represses cholesterol accumulation, and modulates the expression of genes involved in reverse cholesterol transport in macrophages, without inducing hepatic lipogenesis. The induction of Insig-2a suppressed the nuclear translocation of SREBP-1c.
Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
Minh-Hien
MH
Hoang
Yaoyao
Y
Jia
Hee-jin
HJ
Jun
Ji Hae
JH
Lee
Kwang-Yeon
KY
Hwang
Dal-Woong
DW
Choi
Soo-Jong
SJ
Um
Boo-Yong
BY
Lee
Sang-Guan
SG
You
Sung-Joon
SJ
Lee
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D020895:Enterocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008066:Lipolysis; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013654:Taurine / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D000071518:Liver X Receptors; D008565:Membrane Proteins; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D013654:Taurine; D002784:Cholesterol