Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice

摘要

In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enhances susceptibility of the offspring to hypertension,ntype 2 diabetes and other features of the human metabolic syndrome in adulthood. However, previous experimental studies were confined to shorttermnmodifications of the maternal diet during pregnancy and/or lactation periods, a situation uncommon in humans. Moreover in humans, thenoffspring may also consume a high-fat diet, which may take them beyond the range to which their development has adapted them to respondnhealthily. We examined in C57 mice the effects on offspring of feeding their mothers a high-fat (HF) or standard chow (C) diet from weaningnthrough pregnancy and lactation, and whether there are additive phenotypic effects of feeding the offspring an HF diet from weaning to adulthoodn(dam–offspring dietary group HF-HF). This group was compared with offspring from HF-fed dams fed a C diet from weaning to adulthood (HF-C)nand offspring from C-fed mothers fed the C or HF diet (C-C and HF-C, respectively). HF-HF, HF-C and C-HF adult female offspring were heavier,nfatter, and had raised serum cholesterol and blood pressure compared with C-C female offspring. We observed a similar trend in male offspringnexcept for the HF-C group which was not heavier or fatter than male C-C offspring. Histology showed lipid vacuoles within hepatocytes in the HFHF,nHF-C and C-HF but not the CC offspring. Serum C-reactive protein was elevated in female (C-HF and HF-HF) but not in male offspring.nElevated blood pressure in the HF-C and C-HF groups was attenuated in the HF-HF group in males but not in females. These findings indicatenthat long-term consumption of an HF diet by the mother predisposes her offspring to developing a metabolic syndrome-like phenotype in adult life,nalthough cardiovascular effects of an HF diet are related to sex specificity in the HF-HF group.