Abstract
BackgroundEndometriosis is an estrogen dependent, inflammatory disorder occurring in 5–10% of reproductive-aged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. Previously, we identified microRNAs that are differentially expressed in endometriosis and altered in the serum of women with the disease. Here we explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number.MethodsPrimary adipocyte cells cultured from 20 patients with and without endometriosis were transfected with mimics and inhibitors of microRNAs 342-3p or Let 7b-5p to model the status of these microRNAs in endometriosis. RNA was extracted for gene expression analysis by qRT-PCR. PCNA expression was used as a marker of adipocyte proliferation. Endometriosis was induced experimentally in 9-week old female C57BL/6 mice and after 10 months fat tissue was harvested from both the subcutaneous (inguinal) and visceral (mesenteric) tissue. Adipose-derived mesenchymal stem cells in fat tissue were characterized in both endometriosis and non-endometriosis mice by FACS analysis.ResultsGene expression analysis showed that endometriosis altered the expression of Cebpa, Cebpb, Ppar-γ, leptin, adiponectin, IL-6, and HSL, which are involved in driving brown adipocyte differentiation, appetite, insulin sensitivity and fat metabolism. Each gene was regulated by an alteration in microRNA expression known to occur in endometriosis. Analysis of the stem cell content of adipose tissue in a mouse model of endometriosis demonstrated a reduced number of adipocyte stem cells.ConclusionsWe demonstrate that microRNAs Let-7b and miR-342-3p affected metabolic gene expression significantly in adipocytes of women with endometriosis. Similarly, there is a reduction in the adipose stem cell population in a mouse model of endometriosis. Taken together these data suggest that endometriosis alters BMI in part through an effect on adipocytes and fat metabolism.
Highlights
Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5–10% of reproductiveaged women
To test the effect of miRNAs Let-7b and 342-3p on adipocytes, we transfected these miRNA mimics as well as their inhibitors in primary adipocyte cells cultured from fat tissue of women without endometriosis and examined genes known to be key mediators of adipocyte differentiation that are predicted targets of these microRNAs
Expression levels of CCAAT/ enhancer binding protein alpha (Cebpa) and beta (Cebpb), peroxisome proliferator-activated receptor gamma (Ppar-γ), leptin, adiponectin (Adipoq), interleukin-6 (IL-6), and hormone-sensitive lipase (HSL) genes were analyzed by qRT-PCR
Summary
Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5–10% of reproductiveaged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. We explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number. Endometriosis is a gynecological disorder characterized by the deposition and proliferation of endometrial cells or tissue outside the uterine cavity [1, 2] that occurs in 10% of reproductive-aged women [3]. MSCs are progenitor cells that are part of the stroma surrounding the mature adipocyte and preserve tissue homeostasis by regulating the number of mature adipose cells [11]. The reasons for diffuse symptoms and the precise pathophysiology of endometriosis are still not well understood [18]; inappropriate stem cell trafficking and stem cell defects are part of the pathophysiology of this disease and could affect adipose stem cell trafficking as well [19]
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