NDLI: Pitavastatin ameliorates severe hepatic steatosis in aromatase-deficient (Ar−/−) mice

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Lipids : Volume 38, Issue 4, April 2003

Lipids : Volume 38, Issue 3, March 2003

Lipids : Volume 38, Issue 2, February 2003

Lipids : Volume 38, Issue 1, January 2003

Pitavastatin ameliorates severe hepatic steatosis in aromatase-deficient (Ar−/−) mice

Content Provider	Springer Nature Link
Author	Egawa, Tetsu Toda, Katsumi Nemoto, Yoshihisa Akisawa, Naoaki Saibara, Toshiji Hayashi, Yoshihiro Hiroi, Makoto Enzan, Hideaki Onishi, Saburo
Copyright Year	2003
Abstract	Tamoxifen is a potent antagonist of estrogen, and hepatic steatosis is a frequent complication in adjuvant tamoxifen for breast cancer. Impaired hepatic FA β-oxidation in peroxisomes, microsomes, and mitochondria results in progression of massive hepatic steatosis in estrogen deficiency. This impairment, although latent, is potentially serious: About 3% of the general population in the United States is now suffering from nonalcoholic steatohepatitis associated with obesity and hyperlipidemia. Therefore, in the present study we tried to restore impaired hepatic FA β-oxidation by administering a novel statin, pitavastatin, to aromatase-deficient (Ar−/−) mice defective in intrinsic estrogen synthesis. Northern blot analysis of Ar−/− mice liver revealed a significant restoration of mRNA expression of essential enzymes involved in FA β-oxidation such as very long fatty acyl-CoA synthetase in peroxisome, peroxisomal fatty acyl-CoA oxidase, and medium-chain acyl-CoA dehydrogenase. Severe hepatic steatosis observed in Ar−/− mice substantially regressed. Consistent findings were obtained in the in vitro assays of FA β-oxidation activity. These findings demonstrate that pitavastatin is capable of restoring impaired FA β-oxidation in vivo via the peroxisome proliferator-activated receptor-α-mediated signaling pathway and is potent enough to ameliorate severe hepatic steatosis in mice deficient in intrinsic estrogen.
Starting Page	519
Ending Page	523
Page Count	5
File Format	PDF
ISSN	00244201
Journal	Lipids
Volume Number	38
Issue Number	5
e-ISSN	15589307
Language	English
Publisher	Springer-Verlag
Publisher Date	2003-01-01
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Nutrition Bioorganic Chemistry Medicinal Chemistry Medical Biochemistry Biochemistry Microbial Genetics and Genomics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Organic Chemistry Biochemistry

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