Adipocyte alterations in endometriosis: reduced numbers of stem cells and microRNA induced alterations in adipocyte metabolic gene expression

Abstract

Background Endometriosis 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. Methods Primary 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. Results Gene 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. Conclusions We 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.

Correlation of fecal metabolomics and gut microbiota in mice with endometriosis

“…In addition, some studies show that EMS is related to abnormal lipid metabolism, which is manifested by the low body mass index, decreased body fat in human, 33 decreased number of adipocyte stem cells, and disorder of lipid metabolism in the animal model. 34 CDCA and UDCA can improve lipid metabolism and reduce cholesterol saturation in bile, total cholesterol, and low-density cholesterol. [35][36][37] We have speculated that the change in the species abundance and increased CDCA and UDCA levels may be a self-regulation mode of gut microbiota in EMS mice, which can provide the necessary energy to adapt to the inflammatory response by mobilizing lipid metabolism.…”

“…In addition, some studies show that EMS is related to abnormal lipid metabolism, which is manifested by the low body mass index, decreased body fat in human, 33 decreased number of adipocyte stem cells, and disorder of lipid metabolism in the animal model 34 . CDCA and UDCA can improve lipid metabolism and reduce cholesterol saturation in bile, total cholesterol, and low‐density cholesterol 35‐37 .…”

The Formidable yet Unresolved Interplay between Endometriosis and Obesity

“…The biological function of microRNAs is a promising contemporary concept in the pathophysiology of endometriosis [ 32 ]. Zolbin et al demonstrated that the upregulation (miR-342-3p) or inhibition (Let-7b) of microRNAs seen in endometriosis significantly alters the expression of adipocyte genes related to brown adipocyte differentiation ( Cebpa/b and Ppar-γ ), fat metabolism ( IL- 6, HSL ), and glucose metabolism ( leptin and adipoq ) [ 33 ]. However, this relationship does not seem to be reciprocal: Holdsworth-Carlson found no significant impact of obesity on endometrial gene expression, even after stratification for BMI or severity of endometriosis [ 34 ].…”

Clinical characteristics of perineal endometriosis: A case series

“…All 14 patients in this study had PEM secondary to a lateral episiotomy or laceration and the incubation period ranged from 2 mo to 69 mo after surgery. Current studies indicate that the occurrence and severity of pelvic EM are negatively correlated with BMI and pelvic EM[ 9 , 10 ]. However, due to the lag in diagnosis of pelvic EM, there are no reports on the incubation period of pelvic EM and BMI.…”