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oai:repisalud.isciii.es:20.500.12105/230762024-11-29T17:47:33Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Guerra, C author Koza, R A author Walsh, K author Kurtz, D M author Wood, P A author Kozak, L P funder United States Department of Health and Human Services 2024-09-16T08:16:55Z 2024-09-16T08:16:55Z 1998-11-01 J Clin Invest . 1998 ;102(9):1724-31 10.1172/JCI4532 0021-9738 The Journal of clinical investigation 9802886 https://hdl.handle.net/20.500.12105/23076 When placed in the cold (4 degreesC), 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 beta-oxidation. eng Abnormal nonshivering thermogenesis in mice with inherited defects of fatty acid oxidation. research article