Alternations in hepatic expression of fatty-acid metabolizing enzymes in ArKO mice and their reversal by the treatment with 17β-estradiol or a peroxisome proliferator

Autor: Shizuo Akira, Saburo Onishi, Toshiji Saibara, Kiyoshi Takeda, Teruhiko Okada, Yutaka Shizuta, Katsumi Toda
Rok vydání: 2001
Předmět:
Fatty Acid Desaturases
Male
Apolipoprotein E
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Gene Expression
Biochemistry
Acyl-CoA Dehydrogenase
Mixed Function Oxygenases
Mice
chemistry.chemical_compound
Endocrinology
High-density lipoprotein
Cytochrome P-450 Enzyme System
Aromatase
Mice
Knockout
chemistry.chemical_classification
Estradiol
biology
Fatty Acids
Catalase
Liver
Molecular Medicine
Peroxisome Proliferators
lipids (amino acids
peptides
and proteins)
Cytochrome P-450 CYP4A
Oxidoreductases
Oxidation-Reduction
medicine.drug
medicine.medical_specialty
Saccharomyces cerevisiae Proteins
Lipoproteins
Internal medicine
Coenzyme A Ligases
medicine
Animals
RNA
Messenger
Molecular Biology
Bezafibrate
Fatty acid
Lipid metabolism
Cell Biology
Lipid Metabolism
medicine.disease
Repressor Proteins
Microscopy
Electron
chemistry
biology.protein
Acyl-CoA Oxidase
Steatosis
Lipoprotein
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 79:11-17
ISSN: 0960-0760
DOI: 10.1016/s0960-0760(01)00135-2
Popis: We generated aromatase gene knockout mice (ArKO mice) by targeting disruption of Cyp19, which encodes an enzyme responsible for conversion of androgens to estrogens. We found that ArKO males developed hepatic steatosis spontaneously with aging, indicating that the function of Cyp19 is required to maintain constitutive lipid metabolism in male mice. Plasma lipoprotein analysis using a gel permeation chromatography revealed that high density lipoprotein (HDL)-cholesterol levels were slightly higher in ArKO males than in wild-type males, whereas no other obvious alternations in the profiles were detected. Nevertheless, analysis of lipoprotein compositions by SDS-polyacrylamide gel electrophoresis demonstrated apparent reduction in the amounts of apolipoprotein E, functioning in receptor-mediated clearance of lipoproteins in the liver, in the IDL/LDL fraction of ArKO males as compared with that of wild-type males. Biochemical analysis on the ArKO livers revealed suppression of mRNA expression and activity of enzymes involved in fatty acid beta-oxidation. The impairment was reversed to the wild-type levels by treatment with 17beta-estradiol or bezafibrate, the latter is a synthetic peroxisome proliferator. These findings indicated a pivotal role of estrogen in supporting constitutive hepatic expression of genes involved in fatty acid beta-oxidation and in maintaining lipid homeostasis.
Databáze: OpenAIRE
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