ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This genetic epidemiology study genotyped n=248 unrelated children aged 9-12 years, computed 4 weighted polygenic risk scores (PRS), and investigated the associations between (1) appetitive traits and BMI, (2) PRSs and BMI, and (3) PRSs and appetitive traits. Appetite traits were evaluated using an obesogenic appetite score, which was calculated by combining mean scores of the food approach and food avoidance domains from the Child Eating Behavior Questionnaire. There were positive associations between (1) appetitive traits and BMI, (2) between all 4 PRSs and BMI, and (3) between 3 PRSs and appetitive traits. Notably, a significant partial mediation of the PRS-BMI association by the obesogenic appetite score was identified for 3 PRSs, accounting for 11.3% and 21.3% of the total association, depending on the PRS used.

A previous cross-sectional survey of n=5275 adolescents with obesity identified the inability to control appetite and hunger as the main barrier to successful weight reduction [1]. Insights from patients with rare forms of monogenic obesity have underscored the profound impact of genetic variants in the regulation of hunger and satiety in the hypothalamus, leading to weight gain when these processes are disrupted [2]. However, these rare genetic variants are typically found in individual cases, suggesting that “common” obesity results from complex interactions between genetic susceptibility and exposure to an obesogenic environment. The Behavioural Susceptibility Theory offers a possible explanation for the development of “common” obesity in children. It posits that genetic factors can lead to variations in appetite and, in combination with the availability of higher palatable food, e.g. in an obesogenic environment, promote unfavourable eating behaviour and increase energy intake relative to energy expenditure and consequently weight [2, 3].

These findings support the Behavioural Susceptibility Theory by providing evidence for gene-appetite-environment interactions and contributes to our understanding of the underlying mechanism of obesity. However, further research with larger populations is needed to generalize the findings and to develop appropriate implications for policy and individual lifestyle interventions.

References: 1. Halford, J.C.G.; Bereket, A.; Bin-Abbas, B.; Chen, W.; Fernández-Aranda, F.; Garibay Nieto, N.; López Siguero, J.P.; Maffeis, C.; Mooney, V.; Osorto, C.K.; Reynoso, R.; Rhie, Y.J.; Toro-Ramos, M.; Baur, L.A. Misalignment among adolescents living with obesity, caregivers, and healthcare professionals: ACTION Teens global survey study. Pediatr Obes. 2022 Nov;17(11):e12957. doi:10.1111/ijpo.12957.2. Loos, R.J.F.; Yeo, G.S.H. The genetics of obesity: from discovery to biology. Nat Rev Genet 23, 120–133 (2022). https://doi.org/10.1038/s41576-021-00414-z.3. Llewellyn, C.; Wardle, J. Behavioral susceptibility to obesity: Gene-environment interplay in the development of weight. Physiol Behav. 2015 Dec 1;152(Pt B):494-501. doi:10.1016/j.physbeh.2015.07.006.4. Llewellyn, C.H.; Kininmonth, A.R.; Herle, M.; Nas, Z.; Smith, A.D.; Carnell, S.; Fildes, A. Behavioural susceptibility theory: the role of appetite in genetic susceptibility to obesity in early life. Philos Trans R Soc Lond B Biol Sci. 2023 Sep 11;378(1885):20220223. doi:10.1098/rstb.2022.0223.