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Published ahead of print on August 1, 2003, doi:10.1165/rcmb.2003-0235OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 2, February 2004, 174-183

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Submitted on June 24, 2003
Revised on July 31, 2003

Lipogenesis in fetal rat lung: Importance of C/EBP{alpha}, SREBP-1c, and stearoyl-CoA desaturase

Feijie Zhang1, Tianli Pan1, Larry D Nielsen1, and Robert J Mason1*

1 Medicine, National Jewish Medical and Research Center, Denver, CO, United States

* To whom correspondence should be addressed. E-mail: masonb{at}njc.org.

Alveolar type II cells increase lipogenesis and convert glycogen into the phospholipids of surfactant in the late term fetal lung. Recent studies suggest that C/EBP isoforms and SREBP-1c regulate fatty acid synthesis in adult type II cells in vitro. To define the temporal relationships and enzymes involved in lipogenesis in fetal rat lung, the mRNA levels of selected transcription factors and enzymes were determined. There was an increase in the mRNA levels of C/EBP{alpha}, C/EBP{beta}, C/EBP{delta}, PPAR{gamma}, and SREBP-1c but not SREBP-1a or SREBP-2 from fetal day 19 to 21. There was also an increase in the mRNA levels of fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD-1), fatty acid translocase, glycerol-3-P acyl transferase and phosphatidate cytidylyltransferase. By in situ hybridization, there was detectible expression of FAS, SCD-1, and C/EBP{alpha} along the alveolar septae with the same distribution pattern as SP-C, whereas PPAR{gamma} expression appeared to be restricted to macrophages. Regulation of lipogenesis at the mRNA level is predominately on enzymes of fatty acid synthesis and appears to be regulated by C/EBP{alpha} and SREBP-1c. SCD-1 and phosphatidate cytidylyltransferase are important components of the lipogenic response in the fetal lung that have not been recognized previously.




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