Location: Boston, MassachusettsTitle: Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity) Author
Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2011
Publication Date: 1/11/2012
Citation: Smith, C.E., Ordovas, J.M., Sanchez-Moreno, C., Lee, Y., Garaulet, M. 2012. Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity. International Journal of Obesity. 36(1):130-136. Interpretive Summary: The causes underlying weight gain are multi-factorial, and are generally recognized to include both genetics and environment. One of the ways by which genetic variants may contribute to obesity risk is through modulation of eating behavior. Although behaviors which increase the likelihood of obesity have been widely documented, relationships between genetic obesity variants and specific eating behaviors are largely unexplored. In the current study, we investigated relationships between eating behaviors which increase obesity risk and a genetic variant which has been shown to be associated with obesity. The genetic variant, APOA2 m265, was previously demonstrated in multiple populations to increase body mass index in individuals consuming a high saturated fat diet. We detected relationships between APOA2 m265 and eating behaviors which increase risk of obesity including: 1) Skipping meals and 2) Not planning meals in advance. We also investigated relationships between the same genetic variant and plasma concentration of ghrelin (a hormone which has been shown to influence hunger) and saturated fat intake. Saturated fat intake moderates the relationship between genotype and ghrelin, suggesting ghrelin as a potential mechanism by which saturated fat interacts with APOA2 to increase obesity risk. APOA2 m265 genotype may be associated with eating behaviours and dietary modulation of plasma ghrelin. Expansion of knowledge of APOA2 and obesity to include modulation of specific behaviours and hormonal mediators not only broadens understanding of gene-diet interactions, but also facilitates the pragmatic, future goal of developing dietary guidelines based on genotype.
Technical Abstract: New obesity loci continue to be identified through genomewide association studies in populations of increasing size and ethnic diversity but understanding of the mechanisms by which known genetic variants contribute to obesity remains limited. Several well-established obesity candidates encode proteins that appear to modulate obesity risk via energy intake, a key determinant of obesity risk. However, specific behaviours that underlie increased intakes are largely unexplored from the perspective of genetics. Although association studies evaluating genes, energy intake and obesity often interpret relationships without the benefit of detailed behavioural data, behavioural scientists have identified a range of specific eating behaviours that contribute to obesity. Complementing the large number of studies defining obesity–behaviour linkages are those which investigate the heritability of specific behaviours using population and twin data. Patterns of eating including restrained and emotional eating, externally cued overeating and appetitive behaviours appear to be moderately to highly heritable. Identification of genetic variants that may contribute to the heritability of eating patterns will require focused attention on specific variants with demonstrated roles in energy intake and obesity. One candidate that alters obesity risk via altered energy intake is apolipoprotein A-II (APOA2), which is encoded by APOA2. APOA2, a major component of high-density lipoprotein (HDL) particles, is a regulator of triglyceride metabolism and postprandial metabolism for which connections between serum APOA2 concentration, alcohol intake and body mass index (BMI) were initially described nearly two decades ago. More recently, relationships between an APOA2 promoter variant and obesity have been clearly demonstrated. First, an association between APOA2 m265>C, energy intake and obesity was shown in a single population, for which higher energy, macronutrient intake and anthropometric traits were detected in homozygous minor allele (CC) carriers. These initial findings were expanded through replication of a gene–diet interaction in three US populations, a Mediterranean population and in Asian Indians in which APOA2 m265 T>C genotype was associated with increased BMI or obesity in the context of high saturated fat intake. Evidence for APOA2 as a modulator of intake and obesity is robust, but relationships between APOA2 m265 T>C genotype and specific eating behaviours are unexplored. Also unidentified are potential hormonal mediators of the APOA2–nutrient interaction. Understanding the mechanisms underlying the relationships between APOA2, intake behaviours and obesity could facilitate the translation of genetic knowledge to more personalized behavioural approaches to reduce obesity. In this study, we evaluated relationships between APOA2 and obesity risk in a Mediterranean population, with particular focus on patterns of eating and ghrelin, a hormonal regulator of food intake.