Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children, with evidence that the maternal diet and the early life nutritional environment are potential risk for such disease. This study was aimed to investigate the effects of maternal high-fat diet (HFD) on the occurrence of NAFLD in offspring rats and the underlying mechanisms. In this study, the incidence of NAFLD was compared in F1 offspring rats between the maternal HFD group and standard chow (SC) group. In addition, the expression levels of inflammatory cytokines in the placenta, in the umbilical cord blood, and in the livers of neonate offsprings were compared between two groups. HepG2 cells were treated with recombinant IL6 (rIL6) to assess stearoyl-CoA desaturase 1 (SCD1) expression and lipid synthesis in an inflammatory condition. Lipid accumulation was assayed in both SCD1 overexpression and interference HepG2 cells as well as in neonatal rats. Our results showed that HFD exposure before and throughout the pregnancy induced the elevated hepatic TG content of F1 neonates. The levels of inflammatory cytokines in the placenta, umbilical cord blood, and the livers of HFD F1 neonates were significantly higher than those of the SC group. In addition, rIL6 treatment led to TG accumulation accompanied by the upregulation of SCD1 in HepG2 cell lines. Overexpression of SCD1 led to the accumulation of TG contents in HepG2 cells, whereas Scd1 knockdown attenuated the effects of rIL6 treatment. Overexpression of SCD1 in F1 neonatal rats led to hepatic lipid accumulation. Our study indicated that maternal HFD led to intrauterine inflammation, which subsequently caused transgenerationally abnormal hepatic lipid metabolism of F1 neonates. This modulation might be mediated by upregulating SCD1 expression in hepatic cells.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a series of hepatic abnormalities including simple hepatic steatosis and non-alcoholic steatohepatitis (NASH) with hepatic fibrosis and chronic inflammation
The Quantitative real-time polymerase chain reaction (Q-PCR) results showed that the genes involved in lipid synthesis and β-oxidation, including Srebp1c, Fasn, stearoyl-CoA desaturase 1 (Scd1), Pparα, Cpt1α, and Acsl3, were upregulated (Figures 1D,E), which was confirmed by western blot results (Figures 1F,G)
The expression of inflammatory cytokines including IL6 and IL-1β was increased in liver tissues of neonatal rats, whereas tumor necrosis factor-α (TNF-α) level has no significant difference between control and high-fat diet (HFD) neonates (Figures 1H–J)
Summary
Non-alcoholic fatty liver disease (NAFLD) is a series of hepatic abnormalities including simple hepatic steatosis and non-alcoholic steatohepatitis (NASH) with hepatic fibrosis and chronic inflammation. NAFLD has become a global health concern It is the second most common indication for liver transplantation in adults [1], adding to the existing global health care burden. Maternal HFD Causes Neonatal NAFLD in the developed world. Obesity is among the major risk factors for the occurrence of NAFLD. Two major damages led to the occurrence of NAFLD, which includes lipid accumulation in the hepatocytes and inflammation injury. Previous studies showed that IL6 was associated with insulin resistance and enhanced obesity and liver steatosis in HFD-fed mice [4]. Our previous results showed that maternal high-fat diet (HFD) during pregnancy resulted in the occurrence of NAFLD in offsprings at weaning
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