Lovastatin does not correct the accumulation of very long-chain fatty acids in tissues of adrenoleukodystrophy protein-deficient mice.
Lovastatin, an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase, normalizes the very long-chain fatty acids (VLCFA) concentrations in fibroblasts and plasma from patients with X-linked adrenoleukodystrophy (X-ALD). The effects of lovastatin on the accumulation of VLCFA in tissues of adrenoleukodystrophy protein (ALDP)-deficient mice were assessed. ALDP-deficient mice were fed chow with 0.01-0.1% lovastatin for 4-8 weeks. The VLCFA concentrations in the plasma, brain, spinal cord, liver and kidneys were measured. Treatment with 0.1% lovastatin significantly reduced body weight and total cholesterol in the plasma of ALDP-deficient mice. Treatment with lovastatin, however, did not correct the accumulation of VLCFA in the plasma or tissues, including the brain and spinal cord. Lovastatin does not affect the accumulation of VLCFA in ALDP-deficient tissues in mice.
Yamada
T
T
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. yamada@neuro.med.kyushu-u.ac.jp
Shinnoh
N
N
Taniwaki
T
T
Ohyagi
Y
Y
Asahara
H
H
Horiuchi
Kira
J
J
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002784:Cholesterol / Q000097:blood; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000172:deficiency*; D051379:Mice; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism; D015431:Weight Loss
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; C489271:Abcd3 protein, mouse; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008565:Membrane Proteins; D002784:Cholesterol; D008148:Lovastatin