Influences of high-fat diet during pregnancy on sterol regulatory pathway and hepatic lipid deposition in male rat offspring / 中华围产医学杂志

ABSTRACT

Objective To analyze the influences of maternal high-fat diet on male rat offspring's blood lipid level and hepatic lipid deposition as well as on the expression of two key factors,sterol regulatory element binding protein-1 (SREBP-1) and SREBP cleavage acting protein (SCAP),involved in hepatic cholesterol regulatory cascade during childhood and adulthood.Methods Pregnant Wistar rats were randomly divided into two groupshigh fat diet (HF) group and normal intake control (NC) group (both n=20).Rats in the HF group were fed with high-fat diet till delivery before changing to a normal-fat diet,while the NC group was given the normal-fat diet all through the study.Male offspring born appropriate for gestational age (AGA) in different feeding groups were randomly selected as experimental subjects.Physical development,serum lipid levels and hepatic lipid deposition at the age of 7 and 24 weeks were compared between offspring of the two groups.Expression of SCAP and SREBP-1 at protein level was detected with immunohistochemistry.T test or Chi-square test was used for statistical analysis.Results The average birth weight of HF group was higher than that of NC group [(6.95± 0.25) vs (6.79 ±0.78) g,t=2.088,P=0.038].Large for gestational age (LGA),AGA and small for gestational age (SGA) offspring accounted for 18.6％ (21/113),77.9％ (88/113)and 3.5％ (4/113) in HF group and 7.6％ (10/132),87.9％ (116/132) and 4.5％ (6/132) in NC group (x2=13.500,P=0.001).At the age of 7 weeks,the offspring's body weight in HF group was higher than that in NC group [(68.78±7.55) vs (66.61 ±3.92) g,t=2.303,P=0.023].At the age of 24 weeks,the body weight,body length and abdominal circumference of adult offspring in HF group were significantly higher than those in NC group [(251.74±24.04) vs (216.24±33.42) g,(22.60±0.79) vs (21.59± 1.34) cm,(17.93±0.59) vs (16.83±0.88) cm;t=2.220,2.379,2.927,all P＜0.05].At the age of 7 weeks,offspring's serum total cholesterol (TC) level in HF group was higher than that in NC group [(1.94±0.62) vs (1.23 +0.77) mmol/L,t=2.379,P＜0.05].At the age of 24 weeks,adult offspring's liver index,serum TC,triglyceride (TG),low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) levels were all higher in HF group than in NC group,while the high density lipoprotein-cholesterol (HDL-C) level was lower in HF group [(2.75±0.31)％ vs (2.46±0.39)％,(1.98±0.14) vs (1.45±0.27) mmol/L,(2.96±0.21) vs (2.71 ±0.29) mmol/L,(0.97±0.32) vs (0.71 ±0.21) mmol/L,(0.81 ±0.13) vs (0.52±0.17) mmol/L,(1.74±0.20) vs (1.59±0.29) mmol/L;t=2.264,2.333,2.359,2.088,5.336,1.994,all P＜0.05].Comparative analysis of nonalcoholic fatty liver disease activity scores (NAS) between the two groups showed that the liver lobular inflammation in HF group's offspring was more severe at both 7 and 24 weeks of age (2.29±0.49 vs 1.92±0.45,2.83±0.47 vs 2.22±0.55;t=2.157,3.251,all P＜0.05).At the age of 24 weeks,adult offspring in HF group also showed higher liver steatosis scores (2.81 ± 0.35 vs 2.25 ± 0.30,t=4.609,P＜0.05).Immunohistochemical detection showed that there was no significant difference in SCAP protein expressions in liver tissues of 7-week-old offspring between the two groups (P＞0.05),but higher expression of SREBP-1 protein was observed in HF group than in NC group [(34.16±5.08)％ vs (18.09±3.99)％,t=9.697,P＜0.05].At the age of 24 weeks,the expression levels of both SCAP and SREBP-1 proteins in liver tissues were higher in HF group than in NC group [(31.22±6.01)％ vs (17.98+7.89)％,(61.33± 16.25)％ vs (29.76± 11.21)％;t=2.303,2.274,both P＜0.05].Conclusions High-fat intake during pregnancy can increase offspring's birth weight and the risk for LGA offspring.Maternal high-fat diet even up-regulates the expression of SCAP and SREBP-1 in male offspring born AGA in childhood and this impact become more obvious when reaching adulthood,resulting in excessive increase of body weight,body length and abdominal circumference and elevated serum lipid level and liver lipid deposition.