Characterization of Estrogen Receptors (ERs) and ER-metabolizing enzymes in Lipedema and Non-Lipedema Adipose Stem Cells (ASCs) and differentiated adipocytes




Walczak, Samantha
Al-Ghadban, Sara
Rinderle, Caroline
Bunnell, Bruce


Journal Title

Journal ISSN

Volume Title



Introduction: Lipedema is a chronic, idiopathic painful disease characterized by an excess of adipose tissue in the lower extremities, commonly misdiagnosed as obesity, lymphedema, or chronic venous insufficiency. As the severity of lipedema worsens patients have reduced mobility, easy bruising, and fatigue and it is thought to resist lifestyle modifications. While treatments such as liposuction can help ease these symptoms, it is not curative, and the underlying etiology is unknown. Hypothesis: As the development of lipedema often begins or worsens during periods of hormonal change such as puberty, pregnancy, or menopause, we hypothesize that alterations in estrogen drive lipedema pathogenesis. Aim: The aim of this study is to characterize the gene expression of estrogen receptors (ER-α and ER-β), G-protein coupled estrogen receptor (GPER), and ER metabolizing enzymes: Hydroxysteroid 17-beta dehydrogenase (HSD17B1, B7, B12), Hormone-sensitive Lipase (LIPE) and Steroid Sulfatase (STS) in ASCs and differentiated adipocytes in BMI and age-matched non-lipedema and lipedema patients. Methods: Cell culture and Oil Red O stain, RNA extraction and RT-PCR assays were used to assess the expression of ERs and the estrogen metabolizing enzymes in ASCs and differentiated adipocytes. Results: ER-α, ER-β, and GPER gene expression were increased in Lipedema ASCs cultured in hormone-depleted media, as well as in differentiated adipocytes compared to non-lipedema corresponding cells. LIPE, STS, HSD17B17, and HSD17B12 gene expression were also increased in Lipedema differentiated adipocytes compared to non-lipedema differentiated adipocytes. In addition, the gene expression of HSD17B1 was increased in Lipedema ASCs cultured in hormone-depleted media compared to non-lipedema ASCs. Conclusion: These results indicate that expression of ERs and estrogen metabolizing enzymes are altered by Lipedema and suggest that estrogen may play a role in adipose tissue dysregulation in lipedema. Exploring this possible etiology further could contribute to the expansion of treatment options and management available to lipedema patients.