As obesity is a powerful risk factor for a variety of diseases, this development represents a tremendous challenge to the healthcare systems worldwide. Such complications are particularly serious if obesity starts early in life and causes long term exposure of organs to excess body fat. There are convincing indications that early life weight gain is a strong influencing factor a later weight and thus contributes to the risk of developing obesity eventually already in childhood (Gillman et al, 2008; Stettler et al, 2010).

Although current knowledge about mechanisms which contribute to early childhood obesity is limited, there is some evidence that fatty acid status may influence the risk to become overweight or obese. Fatty acids influence adipogenesis by binding to PPARgamma and beta/(delta), which act as a regulator of fat cell formation (Spiegelman, 1998), thereby providing a molecular link between fatty acid status and fat cell development. Of particular importance for adipogenesis seems arachidonic acid, the major long chain polyunsaturated fatty acid of the linoleic acid derived n-6 series (Demmelmair et al, 1999). Arachidonic acid is converted into prostacyclin, which stimulates via cAMP production adipose differentiation of primary preadipocytes in cell culture studies (Massiera et al, 2003). In contrast, the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid were found to inhibit the stimulatory effect of arachidonic acid on cAMP production (Massiera et al, 2003).

Based on these findings G. Alihaud developed the hypothesis that a high intake/availability of n-6 polyunsaturated fatty acids is a potent promoter of adipogenesis in vitro and adipose tissue development in vivo (Massiera et al, 2006; Ailhaud et al, 2004).

Although the observed increase of the intake of n-6 fatty acids during the last decades and the increase in childhood obesity agree with this hypothesis (Ailhaud et al, 2008), it has not been tested so far in birth cohorts. By now the importance of the influence of genetic variants of the fatty acid desaturases FADS1 and FADS2 on human fatty acid status primarily in respect to n-6, but also on n-3, long chain polyunsaturated fatty acids has been demonstrated (Glaser et al, 2010). Inclusion of FADS genotype into studies relating fatty acid status to weight development seems important, as this provides the opportunity to identify a relationship between FADS genotype and obesity risk..

Considering the numerous identified and potentially also unidentified factors, which determine anthropometry during infancy and child adequate statistical power has to be achieved. An ideal opportunity to investigate the hypothesis provides combination of several sizable, well characterized birth cohort for an individual subject based metaanalysis.

Aim

To test whether fatty acid status during early life and/or FADS genotype are related to growth during childhood in population based prospective birth cohorts considering further (e.g. diet, socioeconomic status) influencing factors.

Workplan

Data on fatty acid status at various time points during infancy, genotype, parental anthropometry, dietary intake and socioeconomic status shall be combined for analysis from birth cohorts: e.g. ALSPAC (Bristol, UK), Generation R (Rotterdam, NL),

Statistical modelling will start by applying latent cluster structure analyses techniques to study trajectories for height, weight, relative weight (z-scores), and overweight. Further factors will be considered as confounders and/or effect modifiers. Suitable models were described in a recent paper (Rzehak et al, 2009), which has also shown that a study of approximately 1000 subjects has sufficient power to detect small differences in weight gain due to the longitudinal modelling and the continuous outcome. Thus, it can be expected that even a small effect of fatty acid status on anthropometric development can be detected/excluded by studying more than 10 000 subjects, even if not fully standardized measurements of fatty acid status (age of sampling, analytical procedure) and corresponding modelling is needed.

Expected output

Scientific manuscript describing and discussing the relationship between the levels of fatty acids and genotype with infantile anthropometric development, with a focus on the incidence of overweight and obesity, until the age of 10 years.

References

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