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Fatty acyl‐CoA interaction with LXRα
Author(s) -
Kaliappan Alagammai,
Kelzer Matthew S.,
Rider S. Dean,
Hostetler Heather A.
Publication year - 2011
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.25.1_supplement.939.2
Subject(s) - liver x receptor , sterol regulatory element binding protein , acyl coa , chemistry , lipogenesis , adipose tissue , transcription factor , nuclear receptor , fatty acid , biochemistry , lipid metabolism , medicine , endocrinology , biology , gene , enzyme
Liver X Receptor‐α (LXRα), is a ligand activated nuclear receptor predominantly expressed in liver, kidney, intestine, adipose tissue and adrenal glands. Binding of oxysterols to LXR activates transcription of genes which are involved in cholesterol, lipid and carbohydrate metabolism. Previous studies suggested that LXR can also bind unsaturated fatty acids (FA) and inhibit transcription of sterol regulatory element binding protein (SREBP‐1C). However, the significance of this finding is unclear, since another study showed that unsaturated FA inhibition of SREBP‐1c activity is independent of LXRα. Since increased levels of FA and fatty acid derivatives (fatty acyl‐CoAs, FA‐CoA) are associated with several metabolic disorders, the purpose of this study was to examine the interaction of FA and FA‐CoA with recombinantly expressed full‐length, human LXRα. LXRα displayed high affinity for fluorescently labeled saturated C12 and C16 FA‐CoAs (K d = 15–32nM). Circular dichroic spectra confirmed structural changes of LXRα upon binding of unlabelled saturated fatty acyl‐CoA, suggesting that FA‐CoA serve as endogenous ligands for LXRα. Effects of these ligands (FA‐CoA) could alter the regulation of genes involved in metabolism and energy homeostasis. Since FA are readily metabolized in cells, these data may help explain the inconsistency of previous studies. This work was supported by USPHS NIH grant DK77573.