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Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice.
Mol Genet Metab. 2005 Jan; 84(1):39-47.MG

Abstract

Mice deficient for either long-chain acyl-CoA dehydrogenase (LCAD-/-) or very-long-chain acyl-CoA dehydrogenase (VLCAD-/-) develop hepatic steatosis upon fasting, due to disrupted mitochondrial fatty acid oxidation. Moreover, neither mouse model can maintain core body temperature when exposed to cold. We investigated the effects of fasting and cold exposure on gene expression in these mice. Non-fasted LCAD-/- mice showed gene expression changes indicative of fatty liver, including elevated mRNA levels for peroxisome proliferator-activated receptor-gamma (PPARgamma) and genes involved in lipogenesis. In LCAD-/- and VLCAD-/- mice challenged with fasting and cold exposure, expression of fatty acid oxidation genes was elevated in liver, consistent with increased PPARalpha activity. This effect was not seen in brown adipose tissue, suggesting that expression of these genes may be regulated differently than in liver. The effect of acute cold exposure on expression of fatty acid oxidation genes was measured in peroxisome proliferator-activated receptor (PPAR)-alpha-deficient mice (PPARalpha-/-) and controls. In PPARalpha-/- mice, basal expression of the acyl-CoA dehydrogenases was reduced in liver but was not altered in brown adipose tissue. While cold altered the expression of PPARgamma, sterol-regulatory element binding protein-1 (SREBP-1), ATP citrate lyase, and the uncoupling proteins in brown adipose tissue from both PPARalpha-/- and control mice, fatty acid oxidation genes were unaffected. Thus, while fatty acid oxidation appears critical for non-shivering thermogenesis, expression of the acyl-CoA dehydrogenases is not influenced by cold exposure. Moreover, mitochondrial fatty acid oxidation genes are not regulated by PPARalpha in brown adipose tissue as they are in liver.

Authors+Show Affiliations

Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15639194

Citation

Goetzman, Eric S., et al. "Differential Induction of Genes in Liver and Brown Adipose Tissue Regulated By Peroxisome Proliferator-activated Receptor-alpha During Fasting and Cold Exposure in acyl-CoA Dehydrogenase-deficient Mice." Molecular Genetics and Metabolism, vol. 84, no. 1, 2005, pp. 39-47.
Goetzman ES, Tian L, Wood PA. Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice. Mol Genet Metab. 2005;84(1):39-47.
Goetzman, E. S., Tian, L., & Wood, P. A. (2005). Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice. Molecular Genetics and Metabolism, 84(1), 39-47.
Goetzman ES, Tian L, Wood PA. Differential Induction of Genes in Liver and Brown Adipose Tissue Regulated By Peroxisome Proliferator-activated Receptor-alpha During Fasting and Cold Exposure in acyl-CoA Dehydrogenase-deficient Mice. Mol Genet Metab. 2005;84(1):39-47. PubMed PMID: 15639194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice. AU - Goetzman,Eric S, AU - Tian,Liqun, AU - Wood,Philip A, Y1 - 2004/11/11/ PY - 2004/04/13/received PY - 2004/09/09/revised PY - 2004/09/09/accepted PY - 2005/1/11/pubmed PY - 2005/5/27/medline PY - 2005/1/11/entrez SP - 39 EP - 47 JF - Molecular genetics and metabolism JO - Mol Genet Metab VL - 84 IS - 1 N2 - Mice deficient for either long-chain acyl-CoA dehydrogenase (LCAD-/-) or very-long-chain acyl-CoA dehydrogenase (VLCAD-/-) develop hepatic steatosis upon fasting, due to disrupted mitochondrial fatty acid oxidation. Moreover, neither mouse model can maintain core body temperature when exposed to cold. We investigated the effects of fasting and cold exposure on gene expression in these mice. Non-fasted LCAD-/- mice showed gene expression changes indicative of fatty liver, including elevated mRNA levels for peroxisome proliferator-activated receptor-gamma (PPARgamma) and genes involved in lipogenesis. In LCAD-/- and VLCAD-/- mice challenged with fasting and cold exposure, expression of fatty acid oxidation genes was elevated in liver, consistent with increased PPARalpha activity. This effect was not seen in brown adipose tissue, suggesting that expression of these genes may be regulated differently than in liver. The effect of acute cold exposure on expression of fatty acid oxidation genes was measured in peroxisome proliferator-activated receptor (PPAR)-alpha-deficient mice (PPARalpha-/-) and controls. In PPARalpha-/- mice, basal expression of the acyl-CoA dehydrogenases was reduced in liver but was not altered in brown adipose tissue. While cold altered the expression of PPARgamma, sterol-regulatory element binding protein-1 (SREBP-1), ATP citrate lyase, and the uncoupling proteins in brown adipose tissue from both PPARalpha-/- and control mice, fatty acid oxidation genes were unaffected. Thus, while fatty acid oxidation appears critical for non-shivering thermogenesis, expression of the acyl-CoA dehydrogenases is not influenced by cold exposure. Moreover, mitochondrial fatty acid oxidation genes are not regulated by PPARalpha in brown adipose tissue as they are in liver. SN - 1096-7192 UR - https://www.unboundmedicine.com/medline/citation/15639194/Differential_induction_of_genes_in_liver_and_brown_adipose_tissue_regulated_by_peroxisome_proliferator_activated_receptor_alpha_during_fasting_and_cold_exposure_in_acyl_CoA_dehydrogenase_deficient_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(04)00250-1 DB - PRIME DP - Unbound Medicine ER -