Animal models of programming: early life influences on appetite and feeding behaviour

Abstract

Epidemiological observations of associations between early life nutrition and long-term disease risk have prompted detailed experimental investigation of the biological basis of programming. Studies using rodent or large animal models have clearly established the biological plausibility of nutritional programming and are now yielding important information on underlying mechanisms. Nutritional interventions in pregnancy, including global food restriction, protein restriction, micronutrient restriction and excess fat feeding, determine a consistent cluster of disorders in the resulting offspring. The common association of such diverse nutritional disturbances with hypertension, glucose intolerance and adiposity suggests that a small number of simple common mechanisms are active in response to fetal nutrient imbalance. Studies of rodent models indicate that fetal undernutrition determines adult adiposity. It is unclear whether the increase in central adiposity is related to increased food intake or reduced energy expenditure, although evidence exists to suggest that both may act together. Rats subject to intrauterine protein restriction exhibit increased preference for high fat foods. Feeding of energy dense foods to rats that were undernourished in utero promotes a greater degree of obesity than is noted in animals subject to adequate nutrition in fetal life. There is evidence to suggest that programming of appetite may stem from remodelling of hypothalamic structures that control feeding and programming of the expression of genes involved in responses to orexogenic hormones. The early life programming of appetite and obesity is a complex phenomenon and our understanding of how maternal nutrition determines later energy balance is at a very early stage.

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

“…40 Expression of the gal2r gene had been shown to be suppressed in a preliminary DNA microarray study comparing the hypothalamus from LPE males to controls. 41 On this basis, it was considered inappropriate to examine expression of other peptides involved in appetite regulation. Moreover, galanin and galanin receptors are linked to reproductive functions in rats and may be regulated by female sex steroids, which would provide a ready explanation for gender-specific effects of LP exposure on feeding behaviour.…”

“…We have previously noted that the expression of this gene is hugely suppressed in males exposed to LP diet in the early period. 41 H1h knockout mice show reduced rearing behaviour in novel environments 47 and this receptor has also been implicated in regulation of feeding behaviour. 48 Our findings are in contrast to the reports of Breier et al who have reported profound obesity, hyperphagia and increased sedentary behaviour in the offspring of rats subject to global undernutrition in pregnancy.…”

Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic perturbations

“…A number of rodent models have been established and characterized to mimic early imbalanced nutrition in humans, such as by altering uterine blood flow or changing maternal dietary intake during fetal or immediate postnatal stages (Patel & Srinivasan 2002, Armitage et al 2004, Langley-Evans et al 2005, Plagemann 2005, Patel & Srinivasan 2010 and controlling food availability through litter size manipulation (Plagemann et al 1999a,b, Velkoska et al 2005, Xiao et al 2007, BoulluCiocca et al 2008, Glavas et al 2010, Habbout et al 2012. In the latter model, when pups are raised in small litter, e.g.…”

Childhood obesity and adult cardiovascular disease risk: a systematic review

“…The interaction between growth patterns and exposures in each period may be central to the development of obesity and metabolic risk, altering the metabolic response to a subsequent obesogenic environment. 16 The aim of the current review was to systematically and critically appraise the available evidence regarding the relationship between childhood obesity and adult CVD risk. The primary objective was to report on the strength of associations observed between childhood obesity and adult CVD risk.…”