Genetic and Nongenetic Determinants of Regional Fat Distribution

THE ROLE of inherited and nongenetic factors in individual differences observed in the level of sc fat on the trunk and abdominal areas and in the abdominal visceral deposit is reviewed. First, the metabolic and clinical implications of variation in body fat topography are summarized. Second, the results of genetic epidemiology studies on the heritability and other evidence for a role of the genotype in the amount of truncal-abdominal sc fat and abdominal visceral fat are reviewed. Third, the impact of total body fat, age, and gender on regional fat distribution is highlighted. Fourth, adipose tissue lipoprotein lipase activity is considered as a determinant of fat topography, with a discussion of site and gender differences, the effects of steroid hormones, and evidence from genetic epidemiology. Fifth, the contribution of adipose tissue lipolysis is reviewed with an emphasis on the various regulatory factors of the lipolytic pathways including catecholamines, insulin, adenosine, steroids, and other modulators. The role of lipolytic characteristics on fat topography is further assessed by considering changes with age, differences between men and women, effects of excess body fat, and data from heritability studies. Although the study of regional variation of in vitro adipose tissue metabolism has provided valuable information, a better understanding of variation in fat topography and of the role played by adipose tissue in the regulation of whole body carbohydrate and lipid metabolism will likely require extensive in situ and in vivo investigations. Sixth, as enlargement of a specific fat deposit is associated with increases in fat cell size and number, these topics are considered with an emphasis on the role of adipose cell differentiation. Seventh, the importance of blood levels of sex steroids and glucocorticoids for regional fat distribution is discussed. Then, a unifying hypothesis, defined as the hypothalamic arousal and neuroendocrine dysregulation model, is briefly described. Finally, the issue of whether body fat distribution can be altered by caloric restriction or regular exercise is addressed.