Maternal undernutrition leads to elevated hepatic triglycerides in male rat offspring due to increased expression of lipoprotein lipase

Small for gestational age (SGA) at birth increases the risk of developing metabolic syndrome, which encompasses various symptoms including hypertriglyceridemia. The aim of the present study was to determine whether maternal undernutrition during pregnancy may lead to alterations in hepatic triglyceride content and the gene expression levels of hepatic lipoprotein lipase (LPL) in SGA male offspring. The present study focused on the male offspring in order to prevent confounding factors, such as estrus cycle and hormone profile. Female Sprague Dawley rats were arbitrarily assigned to receive an ad libitum chow diet or 50% food restricted diet from pregnancy day 1 until parturition. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to measure the gene expression levels of hepatic LPL at day 1 and upon completion of the third week of age. Chromatin immunoprecipitation quantified the binding activity of liver X receptor-alpha (LXR-alpha) gene to the LXR response elements (LXRE) on LPL promoter and LPL epigenetic characteristics. At 3 weeks of age, SGA male offspring exhibited significantly elevated levels of hepatic triglycerides, which was concomitant with increased expression levels of LPL. Since LPL is regulated by LXR-alpha, the expression levels of LXR-alpha were detected in appropriate for gestational age and SGA male offspring. Maternal undernutrition during pregnancy led to an increase in the hepatic expression levels of LXR-alpha, and enriched binding to the putative LXR response elements in the LPL promoter regions in 3-week-old male offspring. In addition, enhanced acetylation of histone H3 [H3 lysine (K) 9 and H3K14] was detected surrounding the LPL promoter. The results of the present study indicated that maternal undernutrition during pregnancy may lead to an increase in hepatic triglycerides, via alterations in the transcriptional and epigenetic regulation of the LPL gene.