Adriëtte Oostvogels

3 91 pBMI, lipids and offspring’s body composition priming by intrauterine conditions, as in our case for maternal lipid profile. As both maternal lipid levels and pBMI were both independently associated with childhood’s adiposity, and this implies a different (still unknown) mechanistic pathway. In the present study maternal FFA levels during early pregnancy were related to offspring’s adiposity, whereas TG levels were only related to offspring’s WHtR. This was contrary to expectations as there is a strong biochemical link between FFA and TG levels; FFA are often derived from TG, also maternal TG reach the foetus as FFA as TG are lipolysed in the placenta to FFA. Adjustment for confounders strongly attenuated the association between TG and offspring adiposity. It seems that the confounders adjusted for in the present study were relatively important for this association. Several mechanisms (or a combination of them) may underlie our finding that an adverse maternal lipid level programs their offspring for obesity, i.e. programming of the offspring’s eating behavior, adipocyte development, postnatal influences, genetics and epigenetics. First, from animal studies we know that maternal high-fat diet during pregnancy can lead to structural hypothalamic changes 9 as well as to impaired leptin signalling in the arcuate nucleus of the hypothalamus and resistance to the anorectic actions of leptin. 30,31 It is also known that fetal exposure to maternal FFA levels can induce endoplasmic reticulum stress and inflammation, with a subsequent increase in local cytokines in the hypothalamus. 32-35 The hypothalamus is involved in satiety and regulation of glucose and lipid metabolism and distribution of body fat. Therefore, changes in the hypothalamus may alter the eating behavior of the offspring towards an increased food intake and a preference for dietary fat. 9 Second, adverse maternal lipid levels may influence adipose tissue development. 16,36 Early influences on adipocyte differentiation may have lifelong consequences on adiposity as the fat cell number remains stable throughout childhood. Third, the extrauterine environment, such as diet quality and parental behavior towards physical activity, is shared by mother and child and may contribute to the obesity risk. 37,38 Fourth, research among twins shows that about 70% of the individual variation in adiposity between people is apparently due to genetic factors. 39 Although no genetic pathway has yet been established, common genes that are related to both lipid levels and adiposity might be involved. Finally, epigenetics might affect the association between maternal lipid levels during early pregnancy and their offspring’s body composition. However, only limited evidence is available showing that epigenetic modifications are an important mediator between maternal obesity/maternal lipid status and long-term offspring outcomes. 40