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• W2017474218 endingPage "363" @default.
• W2017474218 startingPage "357" @default.
• W2017474218 abstract "The expression of SREBP-1 (sterol-regulatory-element-binding protein-1) isoforms differs between tissues and cultured cell lines in that SREBP-1a is the major isoform in established cell lines, whereas SREBP-1c predominates in liver and most other human tissues. SREBP-1c is transcriptionally less active than SREBP-1a, but is a main mediator of hepatic insulin action and is selectively up-regulated by LXR (liver X receptor) agonists. LXR-mediated transactivation is co-activated by PGC-1α (peroxisome-proliferator-activated receptor-γ co-activator-1α), which displays deficient expression in skeletal-muscle-derived cell lines. In the present paper, we show that PGC-1α expression is also deficient in HepG2 cells and in a human brown adipocyte cell line (PAZ6). In transient transfection studies, PGC-1α selectively amplified the LXR-mediated transcription from the human SREBP-1c promoter in HepG2 and PAZ6 cells via two LXR-response elements with extensive similarity to the respective murine sequence. Mutational analysis showed that the human LXR-response element-1 (hLXRE-1) was essential for co-activation of LXR-mediated SREBP-1c gene transcription by PGC-1α. Ectopic overexpression of PGC-1α in HepG2 cells enhanced basal SREBP-1c and, to a lesser extent, -1a mRNA expression, but only SREBP-1c expression was augmented further in an LXR/RXR (retinoic X receptor)-dependent fashion, thereby inducing mRNA abundance levels of SREBP-1c target genes, fatty acid synthase and acetyl-CoA carboxylase. These results indicate that PGC-1α contributes to the regulation of SREBP-1 gene expression, and can restore the SREBP-1 isoform expression pattern of HepG2 cells to that of human liver." @default.
• W2017474218 created "2016-06-24" @default.
• W2017474218 creator A5001063783 @default.
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• W2017474218 date "2004-07-06" @default.
• W2017474218 modified "2023-10-17" @default.
• W2017474218 title "Restoration of sterol-regulatory-element-binding protein-1c gene expression in HepG2 cells by peroxisome-proliferator-activated receptor-γ co-activator-1α" @default.
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• W2017474218 doi "https://doi.org/10.1042/bj20040173" @default.
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