Lipedema pathophysiology progresses during periods of hormonal fluctuation such as, but not limited to, puberty, pregnancy and menopause. Hence, we and others have postulated that estrogen likely plays a contributory role in cause or exacerbation of lipedema symptoms. In particular, we postulate that aberrant adipose depot estrogen signaling contributes to exacerbated adipose tissue accumulation associated with the disorder. However, the contributory role and possible mechanisms of sex hormones in lipedema progression remain to be elucidated. Here we explore hormonal regulation within adipose adipose depots. Specifically, adipose tissue, much like the reproductive system, functions as a reservoir and location of conversion and release site of hormones.Androgen/estrogen synthesis in adipose tissue contributes to local and systemic hormone action.
Lower body subcutaneous and abdominal adipose tissue was collected from lipedema and control, BMI and age matched patients. We evaluated mechanisms of adipose depot estrogen signaling. Protein concentration of enzymes involved in cellular regulation, activation, conversion or synthesis, of local and peripheral hormones in adipocytes was measured. This included aromatases that change androgens into estrogens, estrogen conversion enzymes and estrogen inhibition enzymes. Concentration of estrogen receptors alpha and beta located in adipocytes and adrenergic receptors responsible for lipolysis or lipogenesis were also measured.
Hormone associated proteins within adipose tissue of lipedema patients were different from controls and varied between stages of the disease. Estrogen receptor alpha concentration progressively increased as the lipedema stage increases, whereas ,in opposition, estrogen receptor beta was attenuated. Hormone conversion enzymes were higher in early stages of lipedema compared with control.
Estrogen receptors and hormone conversion likely contribute to the lipid accumulation associated with lipedema.