Reduced PPARα expression, and hence impaired fatty acid β-oxidation and deposition of TAG in the myocardium, is associated with cardiomyopathy(Reference Finck, Han, Courtois, Aimond, Nerbonne, Kovacs, Gross and Kelly1). Restricting dietary protein intake of pregnant rats induces altered cardiovascular function in the offspring(Reference Langley-Evans2). The present study has investigated the effect of feeding a protein-restricted (PR) diet to pregnant rats on the expression of PPARα and its target genes involved in fatty acid β-oxidation in the heart of the offspring.
Female rats were fed a control (180 g protein/kg) or PR (90 g protein/kg) diet throughout pregnancy. Offspring (seven to twelve per dietary group) were fed the control diet containing 4 (FAT4) or 10 (FAT10) g fat/100 g from weaning until postnatal day 105. Hearts were collected and frozen in liquid N2. mRNA expression of PPARα and its target genes carnitine palmitoyl transferase (CPT)-1 and acyl-CoA oxidase (AOX) was measured by real-time RT–PCR(Reference Burdge, Slater-Jefferies, Grant, Chung, West, Lillycrop, Hanson and Calder3). 5′ RNA ligase-mediated rapid amplification of cDNA ends was used to identify the PPARα transcripts. TAG concentration was determined by GC(Reference Burdge, Slater-Jefferies, Grant, Chung, West, Lillycrop, Hanson and Calder3). Statistical comparisons were by a general linear model.
Two PPARα transcripts corresponding to different 5′ regulatory regions (termed P1 and P2) were identified. Post-weaning diet (PWD) did not alter any of the outcome measures. Based on marginal means, P1 expression was 12% lower and P2 expression was 14% lower in offspring of PR dams. AOX and CPT-1 expression was also lower (9% and 8% respectively) in the offspring of PR dams. Based on marginal means, total TAG concentration was 55% higher in the offspring of PR dams compared with controls.
MD, maternal diet.
* Normalised cycle threshold.
It has been shown for the first time that the maternal PR diet reduces PPARα expression in the offspring. This is accompanied by reduced expression of key target genes in fatty acid β-oxidation, which is consistent with higher TAG deposition. Together these findings suggest that an overall 26% reduction in PPARα P1 and P2 expression induced by maternal undernutrition during pregnancy may restrict the range of substrates for energy production and alter lipid composition in the heart, and so constrain its functional capacity.
The study was funded by the British Heart Foundation, who also provided salary support for J.S.-J., G.B. and M.H.
