Abstract Objective To study the effects of intrauterine growth restriction (IUGR) and high-fat diet on the growth, lipid metabolism, and related hepatic genes in rat offspring. Methods The rat model of IUGR was established by food restriction during the entire pregnancy. After weaning, 32 normal rats and 24 offspring rats with IUGR were randomly allocated to standard diet group or high-fat diet group. At the age of 10 weeks, fasting plasma glucose and blood lipid were examined. Additionally, pathological sections for hepatic tissues were observed, and the transcriptional levels of related hepatic genes were measured. Results At the age of 10 weeks, there was a significant difference in body weight between IUGR rats and normal rats on standard diets, but no significant difference in body weight was observed between the two groups on high-fat diets. Compared with the normal rats, IUGR rats showed increased energy intake and increased levels of fasting plasma glucose, total cholesterol, and triglyceride on both standard and highfat diets. High-fat diets reduced the concentration of serum triglyceride in both normal rats and IUGR rats. IUGR and high-fat diets aggravated the fat accumulation in the liver. Two-factor analysis of variance showed that at the age of 10 weeks, the expression of genes related to lipid metabolism in the liver, PGC-1α, CPT-1, SREBF-2, HMGR, LDLR and SREBF-1, differed significantly between IUGR and normal rats. Compared with standard diets, high-fat diets increased the expression of PPARα, SREBF-1, SREBF-2, ABCG5, and CYP7A1 in both normal rats and IUGR rats. IUGR and high-fat diets had an interactive effect on LDLR expression. Conclusions Hyperlipidemia and fat accumulation in the liver observed in IUGR rats may be related to increased appetite and regulation disorder in genes related to fatty acid oxidation at the transcriptional level. High-fat diets may aggravate fat accumulation in the liver in rats, which may be related to increased expression of genes related to regulation of fatty acid synthesis at the transcriptional level and reduction in secretion of triglyceride.
CHEN Lian-Hui,LIANG Li,ZHU Wei-Fen et al. Effects of intrauterine growth restriction and high-fat diet on serum lipid and transcriptional levels of related hepatic genes in rats[J]. CJCP, 2015, 17(10): 1124-1130.
CHEN Lian-Hui,LIANG Li,ZHU Wei-Fen et al. Effects of intrauterine growth restriction and high-fat diet on serum lipid and transcriptional levels of related hepatic genes in rats[J]. CJCP, 2015, 17(10): 1124-1130.
Salam RA, Das JK, Bhutta ZA. Impact of intrauterine growth restriction on long-term health[J]. Curr Opin Clin Nutr Metab Care, 2014, 17(3):249-254.
[3]
Rueda-Clausen CF, Dolinsky VW, Morton JS, et al. Hypoxia-induced intrauterine growth restriction increases the susceptibility of rats to high-fat diet-induced metabolic syndrome[J]. Diabetes, 2011, 60(2):507-516.
[4]
Zinkhan EK, Chin JR, Zalla JM, et al. Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats[J]. Pediatr Res, 2014, 76(5):432-440.
[5]
Enjoji M, Yasutake K, Kohjima M, et al. Nutrition and nonalcoholic fatty liver disease:the significance of cholesterol[J]. Int J Hepatol, 2012, 2012:925807.
[6]
Neitzke U, Harder T, Plagemann A. Intrauterine growth restriction and developmental programming of the metabolic syndrome:a critical appraisal[J]. Microcirculation, 2011, 18(4):304-311.
Remacle C, Bieswal F, Bol V, et al. Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance[J]. Am J Clin Nutr, 2011, 94(6 Suppl):1846S-1852S.
[9]
Lim JS, Lee JA, Hwang JS, et al. Non-catch-up growth in intrauterine growth-retarded rats showed glucose intolerance and increased expression of PDX-1 mRNA[J]. Pediatr Int, 2011, 53(2):181-186.
[10]
Fukami T, Sun X, Li T, et al. Mechanism of programmed obesity in intrauterine fetal growth restricted offspring:paradoxically enhanced appetite stimulation in fed and fasting states[J]. Reprod Sci, 2012, 19(4):423-430.
[11]
Coupe B, Grit I, Hulin P, et al. Postnatal growth after intrauterine growth restriction alters central leptin signal and energy homeostasis[J]. PLoS One, 2012, 7(1):e30616.
[12]
Nassir F, Ibdah JA. Role of mitochondria in nonalcoholic fatty liver disease[J]. Int J Mol Sci, 2014, 15(5):8713-8742.
[13]
Choi GY, Tosh DN, Garg A, et al. Gender-specific programmed hepatic lipid dysregulation in intrauterine growth-restricted offspring[J]. Am J Obstet Gynecol, 2007, 196(5):e471-e477.
[14]
Musso G, Gambino R, Cassader M. Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis[J]. Prog Lipid Res, 2013, 52(1):175-191.
[15]
Giby VG, Ajith TA. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease[J]. World J Hepatol, 2014, 6(8):570-579.
[16]
Nakamuta M, Fujino T, Yada R, et al. Impact of cholesterol metabolism and the LXRalpha-SREBP-1c pathway on nonalcoholic fatty liver disease[J]. Int J Mol Med, 2009, 23(5):603-608.