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X‐linked adrenoleukodystrophy mice demonstrate abnormalities in cholesterol metabolism
Author(s) -
Weinhofer Isabelle,
Forss-Petter Sonja,
Kunze Markus,
Žigman Mihaela,
Berger Johannes
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.014
Subject(s) - adrenoleukodystrophy , cholesterol , medicine , endocrinology , hmg coa reductase , metabolism , reductase , chemistry , liver x receptor , cholesterol synthesis , biology , biochemistry , peroxisome , enzyme , gene , receptor , nuclear receptor , transcription factor
The neurodegenerative disorder X‐linked adrenoleukodystrophy (X‐ALD) is caused by ABCD1 mutations and characterized by very long‐chain fatty acid (VLCFA) accumulation. Cholesterol‐lowering normalized VLCFA in fibroblasts and plasma of X‐ALD patients. We show that in cultured cells, cholesterol‐loading induces ABCD1 . In X‐ALD mice, plasma cholesterol is elevated and not further increasable by cholesterol‐feeding, whereas hepatic HMG‐CoA reductase and Abcd2 are downregulated. Upon cholesterol modulation, brain VLCFA increased in X‐ALD mice, but decreased in controls. In murine X‐ALD fibroblasts, cholesterol‐lowering did not normalize VLCFA. Thus, ALDP‐deficiency and VLCFA are linked to cholesterol but species differences complicate evaluating cholesterol‐lowering drugs in X‐ALD mice.