Tags

Type your tag names separated by a space and hit enter

Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system.
J Biol Chem. 2003 Nov 21; 278(47):47232-9.JB

Abstract

Peroxisomal beta-oxidation system consists of peroxisome proliferator-activated receptor alpha (PPARalpha)-inducible pathway capable of catalyzing straight-chain acyl-CoAs and a second noninducible pathway catalyzing the oxidation of 2-methyl-branched fatty acyl-CoAs. Disruption of the inducible beta-oxidation pathway in mice at the level of fatty acyl-CoA oxidase (AOX), the first and rate-limiting enzyme, results in spontaneous peroxisome proliferation and sustained activation of PPARalpha, leading to the development of liver tumors, whereas disruptions at the level of the second enzyme of this classical pathway or of the noninducible system had no such discernible effects. We now show that mice with complete inactivation of peroxisomal beta-oxidation at the level of the second enzyme, enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase (L-PBE) of the inducible pathway and D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase (D-PBE) of the noninducible pathway (L-PBE-/-D-PBE-/-), exhibit severe growth retardation and postnatal mortality with none surviving beyond weaning. L-PBE-/-D-PBE-/- mice that survived exceptionally beyond the age of 3 weeks exhibited overexpression of PPARalpha-regulated genes in liver, despite the absence of morphological evidence of hepatic peroxisome proliferation. These studies establish that peroxisome proliferation in rodent liver is highly correlatable with the induction mostly of the L- and D-PBE genes. We conclude that disruption of peroxisomal fatty acid beta-oxidation at the level of second enzyme in mice leads to the induction of many of the PPARalpha target genes independently of peroxisome proliferation in hepatocytes, raising the possibility that intermediate metabolites of very long-chain fatty acids and peroxisomal beta-oxidation act as ligands for PPARalpha.

Authors+Show Affiliations

Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611-3008, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14500732

Citation

Jia, Yuzhi, et al. "Overexpression of Peroxisome Proliferator-activated Receptor-alpha (PPARalpha)-regulated Genes in Liver in the Absence of Peroxisome Proliferation in Mice Deficient in Both L- and D-forms of enoyl-CoA Hydratase/dehydrogenase Enzymes of Peroxisomal Beta-oxidation System." The Journal of Biological Chemistry, vol. 278, no. 47, 2003, pp. 47232-9.
Jia Y, Qi C, Zhang Z, et al. Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system. J Biol Chem. 2003;278(47):47232-9.
Jia, Y., Qi, C., Zhang, Z., Hashimoto, T., Rao, M. S., Huyghe, S., Suzuki, Y., Van Veldhoven, P. P., Baes, M., & Reddy, J. K. (2003). Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system. The Journal of Biological Chemistry, 278(47), 47232-9.
Jia Y, et al. Overexpression of Peroxisome Proliferator-activated Receptor-alpha (PPARalpha)-regulated Genes in Liver in the Absence of Peroxisome Proliferation in Mice Deficient in Both L- and D-forms of enoyl-CoA Hydratase/dehydrogenase Enzymes of Peroxisomal Beta-oxidation System. J Biol Chem. 2003 Nov 21;278(47):47232-9. PubMed PMID: 14500732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system. AU - Jia,Yuzhi, AU - Qi,Chao, AU - Zhang,Zhongyi, AU - Hashimoto,Takashi, AU - Rao,M Sambasiva, AU - Huyghe,Steven, AU - Suzuki,Yasuyuki, AU - Van Veldhoven,Paul P, AU - Baes,Myriam, AU - Reddy,Janardan K, Y1 - 2003/09/18/ PY - 2003/9/23/pubmed PY - 2004/2/5/medline PY - 2003/9/23/entrez SP - 47232 EP - 9 JF - The Journal of biological chemistry JO - J Biol Chem VL - 278 IS - 47 N2 - Peroxisomal beta-oxidation system consists of peroxisome proliferator-activated receptor alpha (PPARalpha)-inducible pathway capable of catalyzing straight-chain acyl-CoAs and a second noninducible pathway catalyzing the oxidation of 2-methyl-branched fatty acyl-CoAs. Disruption of the inducible beta-oxidation pathway in mice at the level of fatty acyl-CoA oxidase (AOX), the first and rate-limiting enzyme, results in spontaneous peroxisome proliferation and sustained activation of PPARalpha, leading to the development of liver tumors, whereas disruptions at the level of the second enzyme of this classical pathway or of the noninducible system had no such discernible effects. We now show that mice with complete inactivation of peroxisomal beta-oxidation at the level of the second enzyme, enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase (L-PBE) of the inducible pathway and D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase (D-PBE) of the noninducible pathway (L-PBE-/-D-PBE-/-), exhibit severe growth retardation and postnatal mortality with none surviving beyond weaning. L-PBE-/-D-PBE-/- mice that survived exceptionally beyond the age of 3 weeks exhibited overexpression of PPARalpha-regulated genes in liver, despite the absence of morphological evidence of hepatic peroxisome proliferation. These studies establish that peroxisome proliferation in rodent liver is highly correlatable with the induction mostly of the L- and D-PBE genes. We conclude that disruption of peroxisomal fatty acid beta-oxidation at the level of second enzyme in mice leads to the induction of many of the PPARalpha target genes independently of peroxisome proliferation in hepatocytes, raising the possibility that intermediate metabolites of very long-chain fatty acids and peroxisomal beta-oxidation act as ligands for PPARalpha. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/14500732/Overexpression_of_peroxisome_proliferator_activated_receptor_alpha__PPARalpha__regulated_genes_in_liver_in_the_absence_of_peroxisome_proliferation_in_mice_deficient_in_both_L__and_D_forms_of_enoyl_CoA_hydratase/dehydrogenase_enzymes_of_peroxisomal_beta_oxidation_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)76016-3 DB - PRIME DP - Unbound Medicine ER -