Maternal High-Fat Diet Leads to Non-alcoholic Fatty Liver Disease Through Upregulating Hepatic SCD1 Expression in Neonate Rats

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.

Medicinal Plants, Phytochemicals, and Their Impacts on the Maturation of the Gastrointestinal Tract

“…Although not expressly investigated in these studies, the reported effects may lead to a decrease or increase in nutrient availability, respectively, which may have potential adverse health effects as reported for similar variations in "normal" nutrients (Agarwal et al, 2018;Baker and Friedman, 2018;Cao et al, 2020).…”

Effects of CRISPR/Cas9-mediated stearoyl-Coenzyme A desaturase 1 knockout on mouse embryo development and lipid synthesis

“…Leptin-deficient ob/ob mice showed lipid accumulation in their livers, and a lack of SCD1 can lead to a significantly decreased body weight ( Cohen, 2002 ). NAFLD in neonate rats could be induced by a maternal high-fat diet through the up-regulation of SCD1 expression ( Cao et al, 2020 ). CRISPR/Cas9-mediated SCD1 deficiency decreased lipid synthesis gene expression and TAG content in goat mammary epithelial cells ( Tian et al, 2018 ).…”

Ethnic disparities in liver fat accumulation in school‐aged children

“…Information on childhood factors, including average hours of exercise and sedentary activities (screen time), diet quality score, and calorie intake, was obtained from postnatal questionnaires around the age of 9 years, except for sugar intake and breastfeeding, which were obtained from postnatal questionnaires about the first year of life (18). Covariates were selected if there were strong correlations with high BMI, liver fat accumulation, and risk of NAFLD (2,(5)(6)(7)12,(27)(28)(29)(30).…”

“…Furthermore, previous studies have suggested that maternal factors, pregnancy factors, or lifestyle factors are associated with liver fat (13)(14)(15)(16)(17)27,28,(39)(40)(41). Factors such as education level of the mother, higher prepregnancy BMI, sugar intake in early life, and sedentary lifestyle have all been associated with a higher risk of developing NAFLD in childhood (13,15,28,39,41).…”