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

Abstract

In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enhances susceptibility of the offspring to hypertension, type 2 diabetes and other features of the human metabolic syndrome in adulthood. However, previous experimental studies were confined to short-term modifications of the maternal diet during pregnancy and/or lactation periods, a situation uncommon in humans. Moreover in humans, the offspring may also consume a high-fat diet, which may take them beyond the range to which their development has adapted them to respond healthily. We examined in C57 mice the effects on offspring of feeding their mothers a high-fat (HF) or standard chow (C) diet from weaning through pregnancy and lactation, and whether there are additive phenotypic effects of feeding the offspring an HF diet from weaning to adulthood (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) and 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, fatter, and had raised serum cholesterol and blood pressure compared with C-C female offspring. We observed a similar trend in male offspring except for the HF-C group which was not heavier or fatter than male C-C offspring. Histology showed lipid vacuoles within hepatocytes in the HF-HF, HF-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. Elevated 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 indicate that long-term consumption of an HF diet by the mother predisposes her offspring to developing a metabolic syndrome-like phenotype in adult life, although cardiovascular effects of an HF diet are related to sex specificity in the HF-HF group.

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…The origin of other metabolic diseases in the adult can be also related with maternal overnutrition, such as hypertension and hyperlipidemia (Elahi et al, 2009) or insulin resistance and diabetes (Samuelsson et al, 2008), and maternal HFD is associated with changes in hypothalamic regulation of body weight and energy homeostasis by altering the expression of leptin receptor, proopiomelanocortin, and neuropeptide Y in the adult offspring (Page et al, 2009). Nevertheless, not all the studies arise to the same conclusion.…”

Both Hepatic Lipogenesis and Beta-Oxidation are Altered in Offspring of Mothers Fed a High-Fat Diet in the First Two Generations (F1 and F2)

“…Offspring of obese mothers is fatter and has the risk of developing fatty liver compared with offspring of lean mothers (Bruce et al, 2009;Elahi et al, 2009). Our study demonstrated the presence of microvesicular hepatocyte steatosis in the offspring of mothers who received the HF diet in both F1 and F2.…”

Decreased basal insulin secretion from pancreatic islets of pups in a rat model of maternal obesity

“…There is substantial evidence that maternal obesity (MO) and a high-fat diet in animal models produce several metabolic abnormalities in the fetus, neonate and adult offspring (Srinivasan et al 2006, Elahi et al 2009). In utero exposure to excess maternal lipids could affect a number of pathways in developing organs, such as the liver, skeletal muscle, adipose tissue, brain and pancreas (Bringhenti et al 2013).…”

“…In utero exposure to excess maternal lipids could affect a number of pathways in developing organs, such as the liver, skeletal muscle, adipose tissue, brain and pancreas (Bringhenti et al 2013). Maternal high-fat diet during pregnancy and lactation induced insulin resistance and deterioration of pancreatic beta cell function in adult offspring in mice (Yokomizo et al 2014), increased adult body weight and fat mass, increased blood glucose and cholesterol levels, and increased lipid deposition (Srinivasan et al 2006, Elahi et al 2009, Bringhenti et al 2013. Our results agree partially with this.…”