Abstract
Peroxisome proliferators-activated receptors (PPAR) are nuclear receptors which by transcription are regulating genes involved in lipid and glucose metabolism as well as in cell growth and inflammation. Perinatal changes in essential fatty acid (EFA) metabolism can program for long-term effects related to the metabolic syndrome in the rat. The aim of the present study was to investigate if similar changes would be induced in the mice and to study gene expression in order to clarify involved metabolic disturbances. Methods: Mice of C57BL/6 strain were given EFA deficient or control diet from day 15 of pregnancy and during lactation. The pups were killed at weaning (3 w) and different organs dissected and frozen in −70° until analysis. Lipids (HPLC and GLC) and PPAR mRNA (real-time PCR) were analysed in liver. Results: The pups of EFA deficient mothers were sign smaller and had lower liver weight, also related to bw than controls. Serum FA showed marked EFA deficiency, mean(SD) linoleic acid (LA) being 1.60(0.07) vs 29.9(2.9) mol% and EFA deficiency index being 3.7(0.5) vs 0.00(0.00) (p < 0.000001). Liver phospholipid (PL) pattern (mg/g liver weight) showed only differences between phosphatidylserine (PS), sphingomyelins (SMs) and phosphatidylglycerol but the FA pattern was markedly changed in most PL. LA was decreased in all PL (p < 0.00001) as was arachidonic acid (AA). The concentration of docosahexaenoic acid (DHA) was decreased in all PL but phosphatidylethanolamine (PE) and SMs and increased in diphosphoglycerol (DPG) (p < 0.0001). The AA/DHA ratio was significantly decreased compared to controls except in SMs, PS and PE. The mRNA expression in the liver of PPARdelta was decreased 0.8 (0.08) vs 1.67 (0.43) (p < 0.005) and PPARgamma increased 1.67 (0.21) vs 0.61 (0.23) (p < 0.0001) but PPARalpha was unchanged. Summary: Selective marked changes in FA composition of PL was associated with different expression of PPAR delta and PPAR gammabut relative preservation of PE and PPAR alpha. Conclusion: Long-term follow up after FA restitution will reveal if the PPAR changes are permanent and related to the long-term effects in metabolism previously found in rats.
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