7. Hereditary SAT diseases
Hereditary SAT disorders such as lipedema, multiple symmetric lipomatosis (MSL), Dercum’s disease, and familial partial lipodystrophy (FPLD) are characterized by a disproportional SAT hypertrophy that can be associated with systemic symptoms (161). Unlike obesity, hereditary SAT disorders are resistant to dietary changes or physical exercise (161). Among them, lipedema is the most prevalent, marked by the enlargement and deposition of subcutaneous adipocytes (161-165). The occurrence of lipedema during hormonal changes in women, such as puberty, pregnancy, or menopause suggests a potential involvement of estrogen in its pathogenesis. However, the underlying pathomechanisms of lipedema development remain unclear (166). Clinical and histological studies do not show any morphological alterations of the vascular/lymphatic system (167). However, recent evidence suggests an immune-related origin, as observed through macrophage infiltration in lipedema AT (167). Furthermore, lipedema-derived ASCs express proliferative markers (Ki67 and CD34) and show an increased adipogenic differentiation potential in 2D cultures (168-170). The specific roles of these cells and their pathophysiological significance remain to be elucidated.
FPLD is a rarer hereditary lipodystrophy associated with the development of metabolic syndromes and cardiovascular disease in affected patients (171, 172). Investigating the pathomechanisms underlying hereditary lipodystrophies in the context of metabolic syndrome can contribute to a better understanding of obesity related metabolic diseases (table 3).