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Decreased nuclear hormone receptor expression in the livers of mice in late pregnancy

Department of Medicine, University of California, San Francisco, and Metabolism Section, Department of Veterans Affairs Medical Center, San Francisco, California

Submitted 22 February 2005 ; accepted in final form 15 January 2006

During the third trimester of pregnancy, there is an increase in serum triglyceride and cholesterol levels. The mechanisms accounting for these changes in lipid metabolism during pregnancy are unknown. We hypothesized that, during pregnancy, the expression of nuclear hormone receptors involved in regulating lipid metabolism would decrease. In 19-day pregnant mice, serum triglyceride and non-HDL cholesterol levels were significantly increased, whereas total cholesterol was slightly decreased, because of a decrease in the HDL fraction. Peroxisome proliferator-activated receptor (PPAR), PPAR/, and PPAR, liver X receptor (LXR) and LXR, farnesoid X receptor (FXR), and retinoid X receptor (RXR), RXR, and RXR mRNA levels were significantly decreased in the livers of 19-day pregnant mice. Additionally, the expressions of thyroid receptor (TR), pregnane X receptor, sterol regulatory element-binding proteins (SREBP)-1a, SREBP-1c, SREBP-2, and liver receptor homolog 1 were also decreased, whereas the expression of TR, constitutive androstane receptor, and hepatic nuclear factor 4 showed no significant change. mRNA levels of the PPAR target genes carnitine-palmitoyl transferase 1 and acyl-CoA oxidase, the LXR target genes SREBP1c, ATP-binding cassettes G5 and G8, the FXR target gene SHP, and the TR target genes malic enzyme and Spot14 were all significantly decreased. Finally, the expressions of PPAR coactivator (PGC)-1 and PGC-1, known activators of a number of nuclear hormone receptors, were also significantly decreased. The decreases in expression of RXRs, PPARs, LXRs, FXR, TRs, SREBPs, and PGC-1s could contribute to the alterations in lipid metabolism during late pregnancy.

farnesoid X receptor; liver X receptor; peroxisome proliferator-activated receptor; retinoid X receptor; lipid metabolism

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