Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction

Obesity is a heterogeneous disease and is associated with comorbidities such as type 2 diabetes mellitus, cardiovascular disease and cancer. Several studies have examined the role of dysfunctional adipose tissue in the pathogenesis of obesity, highlighting the contrasting properties and impact of distinct fat compartments, sometimes with contradictory results. Dysfunctional adipose tissue involves enlargement, or hypertrophy, of pre-existing fat cells, which is thought to confer increases in cardiometabolic risk, independent of the level of obesity per se. In this article, we critically analyze available literature that examined the ability of adipocyte cell size to predict metabolic disease and adipose tissue dysfunction in humans. Many studies demonstrate that increased fat cell size is a significant predictor of altered blood lipid profiles and glucose-insulin homeostasis independent of adiposity indices. The contribution of visceral adiposity to these associations appears to be of particular importance. However, available studies are not unanimous and many fat depot-specific aspects of the relationship between increased fat cell size and cardiometabolic risk or parameters of adipose tissue dysfunction are still unresolved. Methodological factors such as the approach used to express the data may represent significant confounders in these studies. Additional studies should consider the fact that the relationship between fat cell size and common adiposity indices is non-linear, particularly when reaching the obese range. In conclusion, our analysis demonstrates that fat cell size is a significant predictor of the cardiometabolic alterations related to obesity. We propose that adipocyte hypertrophy, especially in the visceral fat compartment, may represent a strong marker of limited hyperplasic capacity in subcutaneous adipose tissues, which in turn is associated with the presence of numerous cardiometabolic alterations.