Prenatal Lipopolysaccharide Exposure Promotes Dyslipidemia in the Male Offspring Rats

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.

In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms

“…Current data may suggest mitochondrial dysfunction from the F2 maternal lineage-mitochondrial stress was showed to activate the NLRP3 complex in aged hematopoietic stem cells, inducing IL-1β production (32). This interpretation is also in line with findings where maternal LPS exposure was associated with mitochondrial DNA abnormalities and metabolic dysregulation in offspring (33). Furthermore, current data specifically suggests that this mechanism may have sex dependency, pointing toward a female-linked intergenerational dysregulation of IL-1β signaling resulting in hyperresponsiveness in subsequent generations.…”

Partial Replacement of Dietary Fat with Polyunsaturated Fatty Acids Attenuates the Lipopolysaccharide-Induced Hepatic Inflammation in Sprague-Dawley Rats Fed a High-Fat Diet

“…LPS has also been reported to influence blood lipid profiles. In a previous study, LPS exposure during pregnancy resulted in dyslipidemia in offspring rats, and dysregulation of blood lipids in offspring exposed to LPS was more prominent following a high-fat diet [61]. Likewise, in this study, LPS stimulation promoted dyslipidemia due to a high-fat diet by increasing TC levels and decreasing non-HDL-C and HDL levels; therefore, the AC and CRF were remarkably higher in the LPS-stimulated rats.…”

LPS versus Poly I:C model: comparison of long-term effects of bacterial and viral maternal immune activation on the offspring

“…Dyslipidemia was found in Sprague Dawley male offspring at the age of 4 and 8 weeks and is related to abnormal mitochondria and disturbed cholesterol metabolism (78).…”