Genetic determinants of regional fat distribution.

Upper body fat and abdominal visceral fat are two obesity-related phenotypes of interest because of their relationships with a variety of metabolic complications. The heritability of the amount of upper body fat or the level of upper body fat relative to lower body fat ranges from approximately 30-50% of the phenotype's age, sex and total body fat adjusted variance. On the other hand, familial studies of abdominal visceral fat reveal that the familial transmission reaches > 50% of the age, sex and total body fat adjusted variance. Complex segregation analysis undertaken with a panel of nuclear families indicates that major genes may account for a significant fraction of the variance in upper body fat and abdominal visceral fat. Two intervention studies conducted with pairs of male identical twins have shown that changes in upper body fat and visceral fat are more similar within pairs than between pairs, either in phenotype increments when challenged by chronic overfeeding, or in adipose tissue losses after exposure to long-term negative energy balance conditions. The evidence accumulated to date is sufficient to justify undertaking a search for the specific genes and molecular markers involved in the heterogeneity commonly observed in human fat topography.