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PMID: 8790349 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 18 ·1996-09-03 ·Pages 9443-8

Miller CW, Ntambi JM

Abstract

Peroxisome proliferators induce stearoyl-CoA desaturase activity (EC 1.14.99.5) in liver [Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim. Biophys. Acta 752, 259-264]. We analyzed the changes in stearoyl-CoA desaturase 1 (SCD1) mRNA to further define the molecular mechanism for the induction of stearoyl-CoA desaturase by peroxisome proliferators. SCD1 mRNA was analyzed from the livers of BALB/c mice that had been fed diets supplemented with clofibrate or gemfibrozil. Clofibrate was found to induce liver SCD1 mRNA levels 3-fold within 6 hr to a maximum of 22-fold in 30 hr. Gemfibrozil administration resulted in a similar induction pattern. This induction is primarily due to an increase in transcription of the SCD1 gene, as shown by nuclear run-on transcription assays and DNA deletion analysis of transfected SCD1-chloramphenicol acetyltransferase fusion genes. The cis-linked response element for peroxisome proliferator-activated receptor (PPAR) was localized to an AGGTCA consensus sequence between base pairs -664 to -642 of the SCD1 promoter. Clofibrate-mediated induction of SCD1 mRNA was shown to be independent of polyunsaturated fatty acids, with peroxisome proliferators and arachidonic acid having opposite effects on SCD1 mRNA levels. Additionally, the activation of SCD1 mRNA by clofibrate was inhibited 77% by cycloheximide administration. Levels of liver beta-actin and albumin mRNAs were unchanged by these dietary manipulations. Our data show that hepatic SCD1 gene expression is regulated by PPARs and suggest that peroxisome proliferators and poly-unsaturated fatty acids act through distinct mechanisms.

MeSH Terms
Animals Arachidonic Acid/pharmacology Base Sequence Chloramphenicol O-Acetyltransferase/genetics Clofibrate/pharmacology Cycloheximide/pharmacology Fatty Acids, Unsaturated/pharmacology Gemfibrozil/pharmacology Gene Expression Regulation, Enzymologic/drug effects Liver/enzymology Mice Mice, Inbred BALB C Microbodies/drug effects Molecular Sequence Data Promoter Regions, Genetic RNA, Messenger/metabolism Receptors, Cytoplasmic and Nuclear/metabolism Stearoyl-CoA Desaturase/genetics Transcription Factors/metabolism Transcription, Genetic/drug effects
Chemicals
Fatty Acids, Unsaturated RNA, Messenger Receptors, Cytoplasmic and Nuclear Transcription Factors Arachidonic Acid Cycloheximide Stearoyl-CoA Desaturase Chloramphenicol O-Acetyltransferase Clofibrate Gemfibrozil
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Miller C W
Department of Biochemistry, University of Wisconsin, Madison 53706, USA.
Ntambi J M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.18.9443
Published
1996-09-03
Pages
9443-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38447
Subset
IM
Grants
NIDDK NIH HHS · DK42825 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.18.9443 PMC Full Text View journal details
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