Abnormal nonshivering thermogenesis in mice with inherited defects of fatty acid oxidation

被引:108
作者
Guerra, C
Koza, RA
Walsh, K
Kurtz, DM
Wood, PA
Kozak, LP
机构
[1] Univ Alabama, Dept Comparat Med, Birmingham, AL 35294 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
thermogenesis; gene mutations; short and long chain acyl CoA dehydrogenase mitochondrial uncoupling protein;
D O I
10.1172/JCI4532
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
When placed in the cold (4 degrees C), BALB/cByJ mice of both genders rapidly lose body temperature as compared with the control strain, C57BL/6J, This sensitivity to cold resembles that previously described for mice with a defect in nonshivering thermogenesis due to the targeted inactivation of the brown adipocyte-specific mitochondrial uncoupling protein gene, Ucp1, Genetic mapping of the trait placed the gene on chromosome 5 near Acads, a gene encoding the short chain acyl CoA dehydrogenase, which is mutated in BALB/cByJ mice, The analysis of candidate genes in the region indicated a defect only in the expression of Acads, Confirmation of the importance of fatty acid oxidation to thermogenesis came from our finding that mice carrying the targeted inactivation of the long chain acyl CoA dehydrogenase gene (Acadl) are also sensitive to the cold, Both of these mutations attenuate the induction of genes normally responsive to adrenergic signaling in brown adipocytes. These results suggest that the action of fatty acids as regulators of gene expression has been perturbed in the mutant mice. From a clinical perspective, it is important to determine whether defects in thermogenesis may be a phenotype in human neonates with inherited deficiencies in fatty acid B-oxidation.
引用
收藏
页码:1724 / 1731
页数:8
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