Adipose tissue is not to be treated as a homogenous organ of identical functionality. Adipose tissue can be divided into specific regions of different localizations with adipocytes differing in their genetical profile, metabolism, autophagic activity and capacity for multiplication - hyperplasia. Visceral and ectopic regions of adipose tissue are characterized by poor capilarization, hypoxia, and the presence of hypertrophic big adipocytes. Adipocytes of these regions show limited inherent capacity for hyperplasia and when exposed for over nutrition are undergoing disruption with consecutive autophagy and macrophage infiltration leading to development of inflammatory conditions as well as increased fibrosis and remodeling of extracellular matrix. Comparatively smaller numerous adipocytes of gluteo-femoral regions are characterized by better insulin sensitivity and ability to buffer the excess of fatty acids preventing lipotoxemia and to react by hyperplasia when exposed to calorie excess. The differences between these two types of adipocytes with different genetic profile and metabolism are parallel with different localization of these two types of adipocytes and are responsible for the difference in pathophysiology between abdominal and gluteofemoral adiposity. The large body of evidence indicates that hypertrophic and hyperplastic obesity correspond to abdominal and gluteophemoral type of obesity and explain the differences in their pathophysiology and comorbidities.