Abstract
Inflammation is critical to the pathogenesis of cardiovascular diseases (CVDs). We have uncovered intrauterine inflammation induced by lipopolysaccharide (LPS) increases CVDs in adult offspring rats. The present study aimed to explore the role of prenatal exposure to LPS on the lipid profiles in male offspring rats and to further assess their susceptibility to high fat diet (HFD). Maternal LPS (0.79 mg/kg) exposure produced a significant increase in serum and hepatic levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate amino transferase as well as liver morphological abnormalities in 8-week-old offspring rats. Meanwhile, disturbed gene expressions involved in hepatic lipid metabolism and related signaling pathways were found, especially the up-regulated very-low density lipoprotein receptor (VLDLR) and down-regulated transmembrane 7 superfamily member 2 (TM7SF2). Following HFD treatment, however, the lipid profile shifts and liver dysfunction were exacerbated compared to the offsprings treated with prenatal LPS exposure alone. Compared with that in control offsprings, the hepatic mitochondria (Mt) in offspring rats solely treated with HFD exhibited remarkably higher ATP level, enforced Complex IV expression and a sharp reduction of its activity, whereas the offsprings from LPS-treated dams showed the loss of ATP content, diminished membrane potential, decline in protein expression and activity of mitochondrial respiratory complex IV, increased level of MtDNA deletion as well. Furthermore, treatment with HFD deteriorated these mitochondrial disorders in the prenatally LPS-exposed offspring rats. Taken together, maternal LPS exposure reinforces dyslipidemia in response to a HFD in adult offsprings, which should be associated with mitochondrial abnormalities and disturbed gene expressions of cholesterol metabolism.
Highlights
Cardiovascular disease (CVD) is a leading cause of death worldwide
Daily food intake of offspring rats among the four groups was not significantly different in mass, HFD and prenatal LPS exposure plus high fat feeding groups both consumed significantly increased calories at the age of 7 and 8 weeks when compared with control or prenatal LPS exposure offspring rats (P < 0.05 or 0.01), because high fat diet is calorically more dense than the control diet (Figures 1C,D)
Offspring with the treatment of maternal LPS exposure and high fat feeding showed significantly increased body weights at 5 (L+H vs. HFD, P
Summary
Cardiovascular disease (CVD) is a leading cause of death worldwide. Despite recent advances in lifestyle changes and pharmacologic treatments, dyslipidemia is the highest contributor to the occurrence of CVD among all modifiable risk factors. Maternal LPS Promotes Dyslipidemia epidemiological evidence has suggested that risk trajectories that cause adult CVD may already be present in the early postnatal period or at birth, and hyperlipidemia in early adulthood can increase long-term risks of coronary heart disease (Barker, 2004; Cleal et al, 2007; Navar-Boggan et al, 2015). We developed a well-characterized rat model of the maternal non-bacterial inflammation induced by lipopolysaccharide (LPS) or zymosan during pregnancy, which displayed elevated blood pressure as early as 6 weeks of age in offspring rats, blood pressure progressively elevated with age (Wei et al, 2007; Hao et al, 2010a). The role of LPS challenge during early life on lipid profiles in adult offspring rats and its underling mechanism remain largely unclear. We hypothesized mitochondrial disorders should contribute to lipid abnormalities in offspring rats from LPSexposed dam
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