Maternal undernutrition during critical windows of development results in differential and sex-specific effects on postnatal adiposity and related metabolic profiles in adult rat offspring

Abstract

It is well established that altered maternal nutrition may induce long-term metabolic consequences in offspring. However, the effects of maternal undernutrition during different developmental windows on sex-specific growth and metabolism in offspring are not well defined. We investigated the effect of moderate maternal undernutrition during pregnancy and/or lactation on postnatal growth and metabolic outcomes in offspring. Wistar rats were randomly assigned to one of four groups: (1) control (CONT) dams fed a standard diet throughout pregnancy and lactation; (2) dams undernourished to 50 % of CONT during pregnancy (UNP); (3) dams fed at 50 % of CONT throughout lactation (UNL); (4) dams fed at 50 % of CONT throughout pregnancy and lactation (UNPL). UNP and UNPL offspring were lighter at birth compared to CONT and UNL. UNL and UNPL offspring were growth restricted at weaning and remained smaller into adulthood. UNP males and females developed increased adiposity and hyperleptinaemia in adulthood compared to all other groups. Adiposity in UNL and UNPL males was similar to CONT offspring. In UNL and UNPL females, adiposity was lower than for CONT females. Markers of bone mass, lipid metabolism and hepatic function were altered in UNP offspring but were similar in UNL and UNPL offspring compared to CONT. Lack of catch-up growth during lactation in offspring of undernourished mothers prevented development of adiposity and related metabolic disorders in later life. These data highlight that the timing and duration of undernutrition during critical windows of development exert differential effects on postnatal outcomes in a sex-specific manner.Key words: Developmental programming: Obesity: Maternal nutrition Obesity and its related metabolic disorders may prove to be the greatest threat to human lifestyle and health in the developed world this century (1) . The incidence of obesity and overweight has risen markedly in Western societies and the trend is mirrored in developing nations that are transitioning to firstworld economies and lifestyles. Of even more concern is the marked increase over the last decade in the prevalence of childhood obesity and concomitant increases in childhood type 2 diabetes. Metabolic disease results from a complex interaction of genetic, physiological, behavioural and environmental factors. There have been numerous hypotheses to explain the dramatic increase of obesity and metabolic disease, including increased food availability and reduced energy expenditures associated with changing work and/or leisure habits. The recent rate at which these diseases have increased suggests that environmental and behavioural influences, rather than genetic causes, are fuelling the present epidemic. A relationship has been established between the periconceptual, fetal and early-infant phases of life and the subsequent development of adult obesity and type 2 diabetes. This relationship, referred to as the 'developmental origins of health and disease' model, speculates that the fetus makes predictive ad...

Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status

“…This has been previously demonstrated in adult offspring from similar IUGR models [23,24] and can be prevented by dietary interventions which avoid catch-up growth during suckling period [24]. These data indicate that perinatal life is a critical developmental window during which the alterations induced by IUGR might further develop.…”

“…To assess our hypothesis we have studied a rat model of IUGR induced by maternal undernutrition during the second half of gestation (MUN), which has been previously demonstrated to program for hypertension and obesity in adult age [5,[21][22][23][24]. In male and female offspring from MUN and Control dams, we have assessed individual plasma biomarkers of oxidative damage and antioxidant capacity and calculated a global score (oxy-score) from them.…”

Low-protein diet in adult male rats has long-term effects on metabolism

“…Our data indicate that protein restriction during the beginning of adulthood changes glucose and energy metabolism, which might persist in the later stage of life even when the LP diet intervention had been removed. Protein malnourishment during pregnancy causes evident obesity when the rodents reach adulthood (Anguita et al 1993, Fernandez-Twinn & Ozanne 2006, Howie et al 2012; however, the current study does not provide strong enough evidence to indicate that a LP diet during young adulthood provokes obesity later in life. The current results indicate the induction of a slight increase in fat tissue, which is supported by a modest increase in insulin blood levels after a glucose bolus infusion.…”

High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life

“…Despite no differences in birth weight between experimental groups, HF-HF offspring started to become heavier 3 wk following weaning. Thus, unlike in some models of intrauterine undernutrition such as maternal protein restriction (3,11,17,31) or caloric restriction (3,11,31), which are often characterized by lower offspring birth weight, offspring born to high-fat/fructose fed mothers, as observed in the present study, seem to exhibit a delayed response with respect to changes in body weight. Similar observations were made in other rodent models of maternal overnutrition (4,10,20,22,27).…”

“…As mentioned earlier, models of intrauterine undernutrition as a result of maternal protein restriction (3,11,17,31) as well as models of maternal overnutrition (4,10,20,22,27) are associated with a cardiometabolic phenotype in the offspring. Our own study, which utilized high-fat/fructose feeding also showed a similar phenotype in the offspring.…”