Obesity has been identified as """"""""one of today's most blatantly visible - yet most neglected - public health problems."""""""" Like most disorders affecting the well-being of the population at-large, obesity is a complex condition in which multiple determinants interact to produce the undesired end-point. More than 1.1 billion people worldwide fall within the classification of overweight or obese. How and why did the world get so fat? The global answer may be simple: Too many calories and too little exercise. However, at the individual level the answer is more complex as shown by the very limited long term success achieved by weight-reducing therapies. We know that at the individual level obesity is determined by a combination of environmental and genetic factors. The heritability of obesity is estimated to range from 0.37 to 0.52. However, much less is known about the precise contribution of specific genes to the current obesity epidemic. Although hundreds of obesity candidate genes have been identified through different metabolic pathways, the fundamental basis of obesity resides with excessive storage of triacylglycerides (TAG) in adipose tissue. The mechanisms that control the storage and release of TAG in lipid droplets are complex and poorly understood;yet, they are likely to be crucial to the understanding of the regulation of energy metabolism and body weight. In this regard, the evolutionarily related family of PAT proteins (Perilipin (PLIN), Adipophilin, TIP47, S3-12) defined by protein sequence similarity and their association with lipid droplets, may play key roles in obesity. We have recently shown that common variants at the PLIN locus were associated with BMI and obesity risk in females from several large population studies, including Whites, Chinese, Indians and Malays. However, nothing is known about the contributions of other PAT genes to obesity. Moreover, information is lacking about the role that PAT genes may play on the longitudinal changes in BMI that take place in modern societies during aging. Finally, the potential interactions between these genes and dietary factors may shed light on the complex relation between dietary intake and body weight changes observed on an individual basis. Therefore, the primary objective of this application is to identify common genetic variants of the PAT family of genes and to relate those variants with anthropometric measures (BMI, waist circumference, visceral and total body fat) and their changes over time in -2600 men and women from the Framingham Heart Study, using the wealth of cross-sectional and longitudinal data available in this study. Moreover, we will evaluate interactions between genetic variants and dietary habits as modulators of obesity and related anthropometric measures. This research has the potential of translating findings of genetic associations and interactions into dietary recommendations for specific groups selected according to their genetic characteristics in order to increase the success of dietary measures aimed to fight the obesity epidemic.
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