Abstract

BackgroundAdult metabolic syndrome may in part have origins in fetal or early life. This study was designed to explore the effect of prenatal exposure to lipopolysaccharide and high-fat diet on metabolic syndrome in offspring rats.Methods32 pregnant rats were randomly divided into four groups, including Control group; LPS group (pregnant rats were injected with LPS 0.4 mg/kg intraperitoneally on the 8th, 10th and 12th day of pregnancy); High-fat group (maternal rats had high-fat diet during pregnancy and lactation period, and their pups also had high-fat diet up to the third month of life); LPS + High-fat group (rats were exposed to the identical experimental scheme with LPS group and High-fat group).ResultsBlood pressure elevated in LPS group and High-fat group, reduced in LPS+High-fat group, accompanied by the increase of serum leptin level in LPS and High-fat group and increase of serum IL-6, TNF-a in High-fat group; both serum insulin and cholesterol increased in High-fat and LPS+High-fat group, as well as insulin in LPS group. HOMA-IR value increased in LPS, High-fat and LPS+High-fat group, and QUICKI decreased in these groups; H-E staining showed morphologically pathological changes in thoracic aorta and liver tissue in the three groups. Increased serum alanine and aspartate aminotransferase suggest impaired liver function in LPS+High-fat group.Conclusion/SignificancePrenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure, insulin resistance and impaired liver function in three-month old offspring rats. The lowered blood pressure might benefit from the predictive adaptive response to prenatal inflammation.

Highlights

  • IntroductionThe pathophysiology of Type 2 diabetes (T2DM) is characterized by a low-grade chronic inflammation, with the release of inflammatory cytokines by innate immune cells (mainly macrophages and dendritic cells) that impair insulin action [1]

  • The pathophysiology of Type 2 diabetes (T2DM) is characterized by a low-grade chronic inflammation, with the release of inflammatory cytokines by innate immune cells that impair insulin action [1]

  • Serum IL-6, TNF-a and leptin concentration Serum IL-6 and TNF-a concentration in High-fat group increased significantly compared with Control group, LPS group and LPS+High-fat group (p,0.01) (Figure 1A and 1B)

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Summary

Introduction

The pathophysiology of Type 2 diabetes (T2DM) is characterized by a low-grade chronic inflammation, with the release of inflammatory cytokines by innate immune cells (mainly macrophages and dendritic cells) that impair insulin action [1]. Accumulating evidence from animal studies suggest that chronic elevation of circulating lipopolysaccharide (LPS), a key component of gram negative bacteria cell walls, is considered to be a causative factor for insulin resistance [2]. Pharmacological and genetic inhibition of LPS-induced inflammation leads to enhanced insulin action [2]. It suggests that inflammation is a mechanism connected with the risk of type 2 diabetes [3]. This study was designed to explore the effect of prenatal exposure to lipopolysaccharide and high-fat diet on metabolic syndrome in offspring rats

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