Elsevier

Clinical Nutrition

Volume 27, Issue 4, August 2008, Pages 623-634
Clinical Nutrition

Original article
Deleterious effects of high-fat diet on perinatal and postweaning periods in adult rat offspring

https://doi.org/10.1016/j.clnu.2008.05.005Get rights and content

Summary

Background & aims

Pre- and postnatal environmental changes can reset the developmental path during intrauterine development leading to obesity and cardiovascular and metabolic disorders later in life. The effects of high-fat diets on body mass, fat mass, the plasma level of glucose, insulin and leptin, as well as the insulin/glucose ratio and cardiovascular parameters in adult rat offspring were studied.

Methods

Pregnant Wistar rats in a standard chow group (SC) or high-fat chow group (HFC), at weaning their SC and HFC offspring were randomly divided into two postnatal groups: fed on SC or HFC. With euthanasia at 6-month-old, three-way ANOVA there were three-factor interactions among gender, perinatal diet and postweaning diet to body mass (BM), BP, left ventricle (LV) thickness, carbohydrate metabolism, plasma corticosterone concentrations and leptin/fat mass/adipocyte size pattern.

Results

HFC/SC and SC/HFC offspring of both genders had high BM and BP, which were increased in HFC/HFC offspring. There was hyperinsulinism, hyperleptinemia, as well as high insulin/glucose ratio and high plasma corticosterone concentrations mainly in HFC/HFC offspring with adipocytes and LV hypertrophy.

Conclusions

Postweaning HFC was deleterious to the health of adult offspring from dams fed HFC during pregnancy and then during the first half of lactation period. HFC administrated in both periods shows supplementary effects, elevating BP with consequent LV hypertrophy, altering carbohydrate metabolism, plasma corticosterone concentrations and disturbing leptin/fat mass/adipocyte size pattern.

Introduction

Obesity and related metabolic disorders are prevalent health issues in modern society and are commonly attributed to lifestyle and dietary factors. Obesity and insulin resistance are both powerful predictors of cardiovascular disease risk.1 Insulin resistance, in uncomplicated obesity, is associated with increased left ventricular mass and precocious changes of left ventricular geometry2 and, at any given degree of obesity, accentuates the risk of cardiovascular events and type 2 diabetes.3, 4 Globally, the prevalence of obesity is escalating, and insulin resistance resulting from increased adipose tissue mass has been identified as a key factor in driving parallel rises in type 2 diabetes prevalence.5

Increasingly women are becoming obese and consuming an energetic or fat-rich diet when pregnant. Other than the immediate risk to the mother's health and pregnancy outcome, there is an increased risk of gestational diabetes and pre-eclampsia, together with other potential consequences.6 There is increasing evidence to suggest, particularly from studies in animals, that fetus exposed to excess maternal nutrition7 may be prone in later life to the cardiovascular disease.

The environmental factors modulating the physiological systems controlling weight regulation and metabolic disorder etiologies, which manifest in adult life, may originate before birth.8 The ‘fetal origins of adult disease’, ‘fetal programming’ or ‘predictive adaptive response’ paradigms are based on pre- and postnatal environmental changes9 resetting the developmental path leading to obesity, cardiovascular and metabolic disorders later in life. The pathogenesis is not based on genetic defects, but rather on altered genetic expression in adaptating to environmental changes during fetal development.10 With the onset of obesity, maladaptive responses to adipose excess result in pathological states of inflammation, coagulopathy, and altered insulin sensitivity.11

Chronic high-fat diet consumption by female rats results in hyperinsulinemia maintenance during the postweaning period,12 causing glucose intolerance and development of obesity for the progeny in adult life.13 Leptin and insulin resistance lead to critical endocrine defects in the pathogenesis of programming-induced obesity and metabolic disorders,10 because these hormones significantly reduce the number of pancreatic polypeptide-positive cells in the pancreatic islets of high-fat diet-fed animals.14 Moreover, postweaning high-fat diets increase plasma concentrations of free fatty acids15 by accelerating the maturation of the hypothalamic-pituitary-adrenal axis (HPA), causing permanent up-regulation of this axis, as well as basal level increases in corticosterone and stress-induced adrenocorticotrophic hormone (ACTH) and corticosterone secretion.15, 16 Also, postnatal overfeeding increases adipose tissue glucocorticoid sensitivity.17

The effect of high-fat diets during early life and/or during postweaning period on body mass, fat mass, plasma level of glucose, insulin and leptin, was investigated and also their effects on the insulin/glucose ratio and cardiovascular parameters in adult rat offspring.

Section snippets

Animals and diet

Wistar rats from colonies maintained at the State University of Rio de Janeiro were kept under controlled conditions (21 ± 2 °C, humidity 60 ± 10%, 12:12 h dark–light cycle and an air replacement cycle 15 min/h) with free access to food and water.

Virgin females were caged with males overnight, with mating confirmed next morning by the presence of vaginal plug or spermatozoa after a vaginal smear. Dams were then housed individually and divided into two groups: standard chow group (SC), or high-fat chow

Results

Data are shown as mean and SEM.

Discussion

HFC was administered during two different periods of rat development: in pregnant and lactating dams and in offspring from postweaning up to 6 months of age. The experiment considered each single period or combined periods resulting in significant differences in offspring and adult body biometry and blood pressure, impaired carbohydrate metabolism and plasma corticosterone concentration, leptin/fat mass/adipocyte size pattern disturbance, as well as LV hypertrophy. These modifications in

Conflict of interest statement

None declared.

Acknowledgements

This work was supported by the agencies CNPq (Brazilian Council of Science and Technology, http://www.cnpq.br) and FAPERJ (Rio de Janeiro State Foundation for Scientific Research, http://www.faperj.br). LBP carried out the studies and sample analyses and drafted the manuscript. MBA conceived of the study and participated in its design and coordination and helped to draft the manuscript. CAML participated in the design of the study, performed the statistical analysis and helped to draft the

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