The genetic influence on body fat distribution

Measures of general adiposity have limitations in the prediction of metabolic complications of obesity. Body fat compartments, such as abdominal visceral fat, interscapular fat, perivascular fat around the brachial artery, perivascular fat around the thoracic artery and liver fat content, correlate better with insulin resistance, glucose intolerance, diabetes and hypertension than body mass index. Finding the origin of specific fat compartments could help in the development of new therapeutic strategies.The profound genetic determination of body fat distribution has been demonstrated in twin studies and complex segregation analyses. Genome-wide association studies delivered clear evidence for an association of specific genes or genetic regions with waist-to-hip ratio, waist circumference, visceral fat area, and pericardial fat determined by computed tomography. Many of these SNPs and genes also associate with metabolic end-points, such as insulin resistance and diabetes. Candidate gene studies also discovered polymorphisms that are suggested to be associated with markers of body fat distribution. Although most of the results of small studies are not replicated, the problem with hypothesis-free approaches is the low effect size of discovered variants and, in most cases, the lack of pathomechanistic explanations. Further studies using more sophisticated methods for the assessment of body fat distribution are needed to advance our knowledge in this field.