Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression by SREBP-1 and PPARalpha.

Matsuzaka T, Shimano H, Yahagi N, Amemiya-Kudo M, Yoshikawa T, Hasty AH, Tamura Y, Osuga J, Okazaki H, Iizuka Y, Takahashi A, Sone H, Gotoda T, Ishibashi S, Yamada N
J Lipid Res. 2002 43 (1): 107-14

PMID: 11792729

In the process of seeking sterol regulatory element-binding protein 1a (SREBP-1a) target genes, we identified and cloned a cDNA clone encoding mouse Delta(5)-desaturase (D5D). The hepatic expression of D5D as well as Delta(6)-desaturase (D6D) was highly activated in transgenic mice overexpressing nuclear SREBP-1a, -1c, and -2. Disruption of the SREBP-1 gene significantly reduced the expression of both desaturases in the livers of SREBP-1-deficient mice refed after fasting. The hepatic expression of both desaturases was downregulated by dietary PUFA, which were reported to suppress SREBP-1c gene expression. Sustained expression of hepatic nuclear SREBP-1c protein in the transgenic mice abolished the PUFA suppression of both desaturases. Although these data suggested that SREBP-1c regulates D5D and D6D expression, there was no difference in either the D5D or D6D mRNA level between fasted and refed normal mouse livers, indicating a mechanism for fasting induction of both desaturases. Administration of fibrate, a pharmacological ligand for peroxisome proliferator activating receptor alpha (PPARalpha), caused a significant increase in expression of both desaturases. The data suggested that D5D and D6D expression is dually regulated by SREBP-1c and PPARalpha, two reciprocal transcription factors for fatty acid metabolism, and could be involved in lipogenic gene regulation by producing PUFA.

MeSH Terms (25)

Amino Acid Sequence Animals CCAAT-Enhancer-Binding Proteins Cloning, Molecular DNA-Binding Proteins Eating Fasting Fatty Acid Desaturases Fatty Acids, Unsaturated Fenofibrate Gene Expression Regulation Gene Expression Regulation, Enzymologic Humans Hypolipidemic Agents Liver Male Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Receptors, Cytoplasmic and Nuclear RNA, Messenger Sterol Regulatory Element Binding Protein 1 Tissue Distribution Transcription Factors

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