Maternal obesity and fetal programming: effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats

Abstract

Srinivasan M, Dodds C, Ghanim H, Gao T, Ross PJ, Browne RW, Dandona P, Patel MS. Maternal obesity and fetal programming: effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats. Am J Physiol Endocrinol Metab 295: E895-E903, 2008. First published August 5, 2008 doi:10.1152/ajpendo.90460.2008.-Our earlier studies have shown that the artificial rearing of newborn rat pups [first generation high carbohydrate (1-HC)] on an HC milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Offspring [second-generation HC (2-HC)] of 1-HC female rats spontaneously acquired the HC phenotype in the postweaning period. In this study, we have characterized the development of the abnormal intrauterine environment in the 1-HC female rats and the effects on fetal development under such pregnancy conditions for the offspring. 1-HC female rats demonstrated hyperphagia on laboratory chow and increased body weight gain beginning from the immediate postweaning period along with hyperinsulinemia and hyperleptinemia. During pregnancy, 1-HC female rats showed several metabolic alterations including increased body weight gain and increased plasma levels of insulin, leptin, proinflammatory markers, and lipid peroxidation products. Although there were no significant changes in the body weights or litter size of term 2-HC fetuses, the plasma levels of insulin and leptin were significantly higher compared with those of control term fetuses. Quantitation of mRNA levels by real-time RT-PCR indicated significant increases in the mRNA levels of orexigenic neuropeptides in the hypothalamus of 2-HC term fetuses. Collectively, these results indicate that the HC diet in infancy results in an adverse pregnancy condition in female rats with deleterious consequences for the offspring.immediate postnatal period; high-carbohydrate diet; fetal adaptations THE INCIDENCE OF OBESITY has reached epidemic proportions in the United States wherein approximately two-thirds of the adult population is classified as being either overweight or obese and only one-third of the adult population is within the normal body mass index range (27). The presence of obesity significantly increases the risk for the onset of several chronic diseases including type 2 diabetes and cardiovascular disorders (16). Hence, there is a sense of urgency for the need to unravel the etiology of the current obesity epidemic.It is recognized that genetic changes alone do not support the observed increases in the incidence of obesity. The search for alternate explanations for the steep increase in the incidence of obesity over a relatively short span of time has implicated the contribution of environmental and behavioral influences to this outcome. In this context, it is of interest to note that epidemiological and experimental studies in animal models have underscored the relationship between early life nutritional experiences and the later development of metabolic diseases. Results from studies on a malnourished or di...

High Dietary Fat Intake during Lactation Promotes Development of Diet-Induced Obesity in Male Offspring of Mice

“…Therefore, expression of Pparg may be promoted by increases in NEFA and insulin levels in offspring. The milk composition also influences NEFA and insulin levels in offspring and is altered by a change in maternal diet (27). In this study, fat and energy in milk of HD-fed dams during lactation were very high compared with those in CDfed dams.…”

Metabolic Programming in the Immediate Postnatal Life

“…HC term fetuses were hyperinsulinemic and HC fetal islets secreted increasing amounts of insulin in the presence of glucose and amino acids [42] . Surprisingly, adaptations supporting hyperphagia were evident in the fetal HC hypothalamus [41] . Although during the suckling period plasma insulin levels in HC pups were similar to those of age-matched control pups (due most likely to a suppressive effect of high-fat/low-carbohydrate content of rat milk), immediately after weaning HC offspring developed hyperinsulinemia which persisted into adulthood.…”

“…The HC intrauterine environment was characterized by hyperinsulinemia, hyperleptinemia, increased plasma levels of several proinflammatory markers and significantly increased body weight compared to control female pregnant rats. Embryo transfer experiments (mother-fed embryos to HC mother and vice versa) indicated that mere fetal development in the adverse intrauterine environment of the HC female rat was sufficient for fetal programming of the offspring [41] . Cross-breeding of HC female rats with normal and HC male rats and cross-fostering of HC offspring by control dams also supported the above observation [Vadlamudi and Patel, unpubl.…”

Impact of maternal obesity on offspring obesity and cardiometabolic disease risk

“…Finally, while for the purposes of this review, we have focussed on animal studies reporting programming effects in the offspring as a consequence of exposure to maternal obesity/high calorie diet during pregnancy alone or during both pregnancy and lactation, the critical importance of nutrition in the early postnatal period has also been demonstrated in a number of animal models. Thus, in rats, offspring exposed to early postnatal overnutrition as a consequence of suckling by mothers on a high-fat diet, as a result of artificial feeding with a high-carbohydrate diet or as a result of rearing in small litters are at increased risk of obesity and cardiometabolic disease (Plagemann et al 1992, Srinivasan et al 2008. Importantly, such effects are also noted in other species including non-human primates, for example overfeeding in the pre-weaning period increases adiposity in female baboons in young adulthood (Lewis et al 1986).…”