Prenatal exposure to undernutrition and programming of responses to high-fat feeding in the rat

Abstract

Fetal undernutrition programmes risk of later metabolic disorders. Postnatal factors modify the programmed phenotype. This study aimed to assess the effects of a postnatal high-fat (HF) challenge on body weight gain, adiposity and gene expression following prenatal undernutrition. Pregnant rats were fed either a control diet or a low-protein (LP) diet, targeted at days 0 -7 (LPE), days 8 -14 (LPM), or days 15-22 (LPL) gestation. At 12 weeks of age offspring were either fed standard laboratory chow diet (4·13 % fat), or a 39·5 % fat diet, for 10 weeks. LP exposure had no effect on weight gain or abdominal fat in males. Females exposed to LP diet in utero exhibited a similar weight gain on HF diet as on the chow diet. Programming of fat deposition was noted in LPE females and males of the LPM and LPL groups (P¼ 0·019). Hypothalamic expression of galanin mRNA was similar in all groups, but expression of the galanin-2 receptor was modified by LP exposure in female offspring. Hepatic expression of sterol response element binding protein (SREBP-1c) was decreased by LP at both the mRNA (P¼ 0·008) and protein (P,0·001) level. HF feeding increased expression of SREBP-1c mRNA three-fold in controls, with little response noted in the LP groups. Interactions of factors such as postnatal diet, age and sex act together with prenatal factors to determine metabolic function and responsiveness at any stage of postnatal life. This study further establishes a role for prenatal nutrition in programming the genes involved in lipid metabolism and appetite regulation. The origins of the metabolic syndrome in humans are complex and multifactorial. The aetiology of all of the components of the syndrome (obesity, hyperinsulinaemia, dyslipidaemia, cardiovascular and renal disease) is likely to involve a variety of influences across the lifespan. The expression of genes that predispose to, or protect against any of these conditions will be modified through interactions with the postnatal lifestyle environment (diet, physical activity and smoking) 1 . It is also becoming clear that the environment encountered in fetal life modifies both gene expression and the nature of the gene -postnatal environment interaction 2,3 . Evidence for this prenatal component of disease risk comes from both epidemiological investigations and experimental studies in animals 4 . Studies with animals show clearly that undernutrition in pregnancy is able to programme raised blood pressure, glucose intolerance, insulin resistance and obesity 5 . Exposure to a low-protein (LP) diet in fetal life programmes a phenotype that resembles the metabolic syndrome in ageing rats 6,7 . In such animals the expression of transcription factors regulating lipogenesis, and their downstream target genes are noted to be suppressed until nine months of age. Over-expression in later adulthood occurs coincident with the appearance of metabolic disorders including hepatic steatosis 6,7 .The transcription factor, sterol response element binding protein (SREBP)-1c, is one of the key regula...

Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism

“…* P \ 0.001 compared to control group. n = 7-9 per group paper indicate that hepatic SREBP-1c expression was decreased in 4-week-old LP-exposed offspring that received vehicle injection, effectively replicating our previous findings [18,28]. This study has demonstrated a potential role for glucocorticoids in mediating the effects of prenatal protein restriction upon expression of SREBP-1c.…”

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease

“…[59,60, Data from animal experimentation have also provided more insights into how nutritional deficiency can induce epigenetic alterations (Table 2). [86][87][88][89][90][91][92][93][94][95] For example, protein restriction in pregnant rodents was shown to produce hypomethylation of the hepatic glucocorticoid receptor (GR) and peroxisome proliferator-activated receptor alpha (PPARα) gene promoters, with consequently increased expression of these genes, [87] even across several generations [88,90] through reprograming of the germline methylation levels. [89] The placenta plays a central role in nutrient transfer between mother and fetus during intrauterine life and helps to maintain pregnancy through other mechanisms, and could be a target of the epigenetic modifications due to starvation mediated via changes to methylation levels of imprinted genes and microRNAs associated with genes involved in a wide range of activities from placental nutrient transfer and fetal development to multiple diseases.…”

“…Dietary protein restriction during pregnancy [86][87][88][89]93] Increased preference for fatty food than high-carbohydrate food in male and female rat offsprings at 12 and 30 weeks [90,94,95] Hypercholesterolemia, hyper-triacylglycerolemia, hyperglycemia, glucose intolerance, hyperinsulinemia and insulin resistance, increased leptin and resistin, increased adiposity, and leptin resistance characterized by altered expression of neuropeptide Y and proopiomelanocortin (POMC) in F1 and F2 offsprings…”

Glucocorticoids: Biochemical Group That Play Key Role in Fetal Programming of Adult Disease

“…The concept of the programming has its roots since 50 years ago (163) and proven by both animal (152,164) and human studies (119,149), however, the mechanism that events during intrauterine life are carried in the memory of every molecule, gene, cell, tissue and systems` organs of the body still not completely revealed. Many hypotheses have been proposed with their inherited power and weakness.…”