Obesity Reduces the Expression of GLUT4 in the Endometrium of Normoinsulinemic Women Affected by the Polycystic Ovary Syndrome
ABSTRACT GLUT4 is the most important glucose transporter in insulin-dependent tissues. A decrease of its expression by the adipocytes was reported in polycystic ovary syndrome (PCOS), regardless of obesity and glucose tolerance. In PCOS, abnormal menstrual cycles, abnormal insulin secretory patterns, and obesity, which are risk factors for endometrial diseases, frequently coexist. The endometrial effects of insulin are direct through specific insulin receptors. However, it is unknown whether the endometrium expresses GLUT4 and can be considered an insulin-regulated tissue. In this study, we investigated this question, and we investigated whether obesity modulates this expression in PCOS normoinsulinemic patients. We assayed GLUT4 in the endometrial samples from 18 normoinsulinemic PCOS patients and 9 controls in the advanced follicular phase of the cycle; 10 patients were lean and 8 obese, and all were aged between 23 and 32 years. Most tissue was immediately frozen for RT-PCR; some tissue was saved for histology and immunohistochemistry. GLUT4 mRNA expression was measured in three samples for every patient and expressed as mean +/- SE of an arbitrary unit. In obese PCOS subjects, endometrial GLUT4 expression was significantly lower than in the lean ones (24.0 +/- 6.8 vs. 65.2 +/- 24.4; P < 0.005) and the controls (53.2 +/- 10.7). Lean PCOS and control subjects showed similar values. GLUT4 immunostaining was strong in the epithelial and absent in the stromal cells. We demonstrated endometrial GLUT4 expression. The similar results in lean PCOS and control subjects suggest that endometrial GLUT4 expression is not affected by PCOS itself, whereas it is reduced by obesity in PCOS patients.
SourceAvailable from: Ruijin Shao[Show abstract] [Hide abstract]
ABSTRACT: Although a number of in vitro studies have demonstrated the antiproliferative, anti-invasive, and antimetastatic effects of metformin in multiple cancer cell types, its cellular and molecular mechanisms of anti-cancer action in the endometrium of women with polycystic ovary syndrome (PCOS) have not yet been fully elucidated. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are known to be involved in metformin uptake and excretion in cells. In this article, we discuss the novel therapeutic possibilities for early-stage endometrial carcinoma (EC) in women with PCOS focusing on metformin, which might have a direct effect in the endometrium through the OCTs and MATEs. We then review the molecular mechanism(s) of the action of metformin in the endometrium and highlight possible mechanistic insights into the inhibition of cell proliferation and tumor growth and, ultimately, the reversal of early-stage EC into normal endometria in women with PCOS.Journal of Experimental & Clinical Cancer Research 05/2014; 33(1):41. DOI:10.1186/1756-9966-33-41 · 3.27 Impact Factor
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ABSTRACT: Obesity-related disorders, especially metabolic syndrome, contribute to 2.8 million deaths each year worldwide, with significantly increasing morbidity. Eating at regular times and proper food quantity are crucial for maintaining a healthy status. However, many people in developed countries do not follow a regular eating schedule due to a busy lifestyle. Herein, we show that a repeated sense of hunger leads to a high risk of developing visceral obesity and metabolic syndrome in a mouse model (both 3-week and 6-week-old age, 10 mice in each group). The ad libitum (AL) group (normal eating pattern) and the food restriction (FR) group (alternate-day partially food restriction by given only 1/3 of average amount) were compared after 8-week experimental period. The total food consumption in the FR group was lower than in the AL group, however, the FR group showed a metabolic syndrome-like condition with significant fat accumulation in adipose tissues. Consequently, the repeated sense of hunger induced the typical characteristics of metabolic syndrome in an animal model; a distinct visceral obesity, hyperlipidemia, hyperglycemia and hepatic steatosis. Furthermore, we found that specifically leptin, a major metabolic hormone, played a major role in the development of these pathological disorders. Our study indicated the importance of regular eating habits besides controlling calorie intake.PLoS ONE 05/2014; 9(5):e98276. DOI:10.1371/journal.pone.0098276 · 3.53 Impact Factor
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ABSTRACT: Successful embryonic implantation is the result of a receptive endometrium, a functional embryo at the blastocyst stage and a synchronized dialog between maternal and embryonic tissues. Successful implantation requires the endometrium to undergo steroid-dependent change during each menstrual cycle, exhibiting a short period of embryonic receptivity known as the window of implantation. The term "endometrial receptivity" was introduced to define the state of the endometrium during the window of implantation. It refers to the ability of the endometrium to undergo changes that will allow the blastocyst to attach, penetrate, and induce localized changes in the endometrial stroma. These changes are metabolically demanding, and glucose metabolism has been proven to be important for the preparation of the endometrium for embryo implantation. Obesity and polycystic ovary syndrome (PCOS) represent 2 common metabolic disorders that are associated with subfertility. The aim of this review is to summarize the effect of obesity and PCOS on endometrial receptivity at the time of implantation. Focus will be on metabolic alterations that regulate decidualization, including glucose metabolism, hyperinsulinemia, and hyperandrogenism. © The Author(s) 2014.Reproductive sciences (Thousand Oaks, Calif.) 12/2014; 22(1). DOI:10.1177/1933719114561552 · 2.18 Impact Factor