The importance of malnutrition and growth during early life for the programming of obesity in adult rat
(2005)
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- Epidemiological evidences suggest that a poor intra-uterine environment elicited by maternal dietary insufficiency or imbalance may programme susceptibility in the fetus to later development of type-2 diabetes, obesity, hypertension and cardiovascular disease. To explain this association, it has been proposed that fetal malnutrition programs the metabolism in a manner beneficial to survive under environment of poor postnatal nutrition. This would give rise to a thrifty phenotype, which would become detrimental if the fetus was born in conditions of either adequate or over-nutrition. We aimed to highlight how adverse intrauterine or postnatal conditions lead to the programming of obesity in adulthood. We firstly investigated, in vitro, if malnutrition during early life altered the programming of adipose precursor cells to divide or store fat. We found that the capacity for proliferation and differentiation of preadipose cells was unchanged in rat offspring submitted to protein restriction (8% vs. 20%) during gestation and/or lactation. Secondly, we studied, in vivo, the respective impact of early malnutrition and postnatal overfeeding on the programming of obesity and its associated metabolic disorders. Two rat models of malnutrition were compared: protein and calorie restriction (50% of ad libitum intake). Our results showed that protein restriction during gestation and lactation led to permanent growth retardation. In such offspring, there was no clue in favour of an early programming of obesity. By contrast, rapid postnatal catch-up growth induced by postnatal overfeeding led to the programming of adult obesity in offspring previously malnourished during fetal life. This was associated with an altered gene expression in adipose tissue, which should participate to the development of cardiovascular disease. Finally, in order to confirm the thrifty phenotype hypothesis, we investigated the long-term impact of fetal adaptations to protein restriction when protein restriction persisted until late adult life. In conclusion, our study indicated that postnatal overfeeding after fetal growth retardation favoured the development of obesity and its associated metabolic disorders in adult life.
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Bieswal, F. (2005). The importance of malnutrition and growth during early life for the programming of obesity in adult rat. https://hdl.handle.net/2078.5/124171