scholarly journals MicroRNA-21 Modulates White Adipose Tissue Browning and Altered Thermogenesis in a Mouse Model of Polycystic Ovary Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A775-A776
Author(s):  
Samar Rezq ◽  
Alexandra M Huffman ◽  
Maryam Syed ◽  
Jelina Basnet ◽  
Jussara M do Carmo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Polycystic Ovary Syndrome ◽  
Fat Mass ◽  
White Adipose Tissue ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Iodothyronine Deiodinase

Abstract Background and Aim: Polycystic ovary syndrome (PCOS) is associated with obesity, and white adipose tissue (WAT) and brown adipose tissue (BAT) dysregulation. However, the molecular mechanisms that mediate WAT and BAT derangements in PCOS are poorly understood. Subcutaneous (SC) WAT (SC-WAT) can transition to a beige/brite adipose tissue phenotype (browning) under altered thermogenic conditions. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in androgen-mediated browning and beiging derangements in both SC-WAT and BAT. Methods: Three week-old miR-21 knockout (miR21KO) or wild type (WT) female mice were treated with dihydrotestosterone (DHT, 8 mg/silastic tube) or vehicle for 90 days (n=12/grp). Body composition was measured by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), and carbon dioxide production (VCO2) were measured by indirect calorimetry. Glucose homeostasis was measured by oral glucose tolerance test (OGTT). HOMA-IR index was calculated from fasting serum glucose and insulin levels. Gene expression for browning (UCP1, Cox7a1, Elov3, Dio2 and Cidea) and beiging (Hspb7 and Txb1) markers was quantified by RT-qPCR in SC-WAT and BAT. Results: DHT increased body weight (25.07 ± 0.52 vs 21.79 ± 0.47 g, p<0.05) and fat mass (4.60 ± 0.46 vs 1.98 ± 0.12 g, p<0.05), impaired OGTT (186.10 ± 5.99 vs 250.70 ± 14.76 mg.min/dL, p<0.05), and did not significantly change EE, VO2 or VCO2 in WT mice. All browning markers were downregulated by DHT in SC-WAT; however, only iodothyronine deiodinase 2 (Dio2) downregulation reached significance in both SC-WAT and BAT (by 53 and 40%, respectively) compared with the vehicle-treated mice. Beiging markers were significantly upregulated in SC-WAT and did not change in BAT. DHT-treated miR21KO mice showed attenuated DHT-mediated increase in body weight (23.84 ± 0.99 vs 25.07 ± 0.52 g, p<0.05) compared with WT mice. MiR-21 ablation did not modify DHT-mediated increase in fat mass or OGTT but worsened insulin resistance as calculated by the HOMA-IR index. Additionally, DHT-treated miR21KO mice showed a trend to reduced EE, VO2 and VCO2 values compared with DHT-treated WT. Gene expression analysis showed an exacerbation in DHT-mediated reduction in browning markers expression in the SC-WAT. Additionally, the induction in the adaptive beiging response was abolished in SC-WAT. Conclusion and Significance: These findings suggest that adipose tissue miR-21 may have a protective role in PCOS and ameliorate the DHT-mediated decrease in energy expenditure. Adipose tissue-specific modulation of miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements. (Supported by NIH grants NIGMS P20GM121334 to LLYC and DGR, NIDDK R21DK113500 to DGR, NIGMS P20GM104357 and NHLBI P01HL51971).

scholarly journals The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Eduardo Spinedi ◽  
Daniel P. Cardinali
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
White Adipose Tissue ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
The Metabolic Syndrome ◽  
Obstructive Sleep ◽  
The Impact

Polycystic ovary syndrome is a highly frequent reproductive-endocrine disorder affecting up to 8–10% of women worldwide at reproductive age. Although its etiology is not fully understood, evidence suggests that insulin resistance, with or without compensatory hyperinsulinemia, and hyperandrogenism are very common features of the polycystic ovary syndrome phenotype. Dysfunctional white adipose tissue has been identified as a major contributing factor for insulin resistance in polycystic ovary syndrome. Environmental (e.g., chronodisruption) and genetic/epigenetic factors may also play relevant roles in syndrome development. Overweight and/or obesity are very common in women with polycystic ovary syndrome, thus suggesting that some polycystic ovary syndrome and metabolic syndrome female phenotypes share common characteristics. Sleep disturbances have been reported to double in women with PCOS and obstructive sleep apnea is a common feature in polycystic ovary syndrome patients. Maturation of the luteinizing hormone-releasing hormone secretion pattern in girls in puberty is closely related to changes in the sleep-wake cycle and could have relevance in the pathogenesis of polycystic ovary syndrome. This review article focuses on two main issues in the polycystic ovary syndrome-metabolic syndrome phenotype development: (a) the impact of androgen excess on white adipose tissue function and (b) the possible efficacy of adjuvant melatonin therapy to improve the chronobiologic profile in polycystic ovary syndrome-metabolic syndrome individuals. Genetic variants in melatonin receptor have been linked to increased risk of developing polycystic ovary syndrome, to impairments in insulin secretion, and to increased fasting glucose levels. Melatonin therapy may protect against several metabolic syndrome comorbidities in polycystic ovary syndrome and could be applied from the initial phases of patients’ treatment.

Depot‐Specific Response of White Adipose Tissue to MicroRNA‐21 Ablation in Polycystic Ovary Syndrome

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Samar Rezq ◽  
Alexandra M. Huffman ◽  
Maryam Syed ◽  
Suman Tiwari ◽  
Jelina Basnet ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
White Adipose Tissue ◽  
Polycystic Ovary ◽  
Specific Response ◽  
Ovary Syndrome

scholarly journals The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome

2020 ◽  
Vol 245 (2) ◽  
pp. 281-289 ◽  
Author(s):  
Xinyu Qi ◽  
Chuyu Yun ◽  
Baoying Liao ◽  
Jie Qiao ◽  
Yanli Pang
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
White Adipose Tissue ◽  
Polycystic Ovary ◽  
Therapeutic Effects ◽  
Ovary Syndrome ◽  
Interleukin 22 ◽  
Immune Factor ◽  
Embryo Number

Polycystic ovary syndrome (PCOS) is a complex syndrome involving both endocrine and metabolic disorders. Gut microbiota and the intestinal immune factor IL-22 play an important role in the pathogenesis of PCOS. However, the therapeutic role of IL-22 in high androgen-induced PCOS mice is not clear. We aimed to determine the therapeutic effects of IL-22 on the DHEA-induced PCOS mouse model and to explore the possible mechanism of IL-22 in regulating hyperandrogenism-associated PCOS. Insulin resistance levels and ovarian functions were investigated in DHEA-induced PCOS mice with or without additional IL-22 treatment. We found that IL-22 could reverse insulin resistance, disturbed estrous cycle, abnormal ovary morphology, and decreased embryo number in DHEA mice. Mechanistically, IL-22 upregulated the browning of white adipose tissue in DHEA mice. This study demonstrated that IL-22-associated browning of white adipose tissue regulated insulin sensitivity and ovarian functions in PCOS, suggesting that IL-22 may be of value for the treatment of PCOS with a hyperandrogenism phenotype.

scholarly journals Androgen Reduces Mitochondrial Respiration in Mouse Brown Adipocytes: A Model for Disordered Energy Balance in Polycystic Ovary Syndrome

2020 ◽  
Vol 22 (1) ◽  
pp. 243
Author(s):  
Avi Lerner ◽  
Drashti Kewada ◽  
Ayan Ahmed ◽  
Kate Hardy ◽  
Mark Christian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Mitochondrial Respiration ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Brown Adipocytes ◽  
Androgen Treatment ◽  
Brown Adipose ◽  
Postprandial Thermogenesis

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including reduced postprandial thermogenesis. Although abnormalities in adipose tissue function have been widely reported in women with PCOS, less is known about direct effects of androgen on white and, particularly, brown adipocytes. The purpose of this study was to investigate the effect of the nonaromatizable androgen dihydrotestosterone (DHT) on (1) lipid accumulation and expression of adipogenic markers in immortalized mouse brown adipose cell lines (IMBATs), (2) mitochondrial respiration in IMBATs, (3) mitochondrial DNA content and gene expression, (4) expression of brown adipose tissue (BAT) markers and thermogenic activation. In addition, we profiled the relative levels of 38 adipokines secreted from BAT explants and looked at androgen effects on adipokine gene expression in both IMBATs and immortalized mouse white adipose (IMWATs) cell lines. Androgen treatment inhibited IMBAT differentiation in a dose-dependent manner, reduced markers of adipogenesis, and attenuated the β-adrenoceptor-stimulated increase in uncoupling protein-1 (UCP1) expression. In explants of mouse interscapular BAT, androgen reduced expression of UCP1, peroxisome proliferator-activated receptor-γ coactivator-1 (PCG-1) and Cidea. Significantly, as well as affecting genes involved in thermogenesis in BAT, androgen treatment reduced mitochondrial respiration in IMBATs, as measured by the Seahorse XF method. The results of this study suggest a role for excess androgen in inhibiting brown adipogenesis, attenuating the activation of thermogenesis and reducing mitochondrial respiration in BAT. Together, these data provide a plausible molecular mechanism that may contribute to reduced postprandial thermogenesis and the tendency to obesity in women with PCOS.

scholarly journals Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

2012 ◽  
Vol 167 (5) ◽  
pp. 705-713 ◽  
Author(s):  
Tao Tao ◽  
Shengxian Li ◽  
Aimin Zhao ◽  
Yanyun Zhang ◽  
Wei Liu
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Subcutaneous Adipose Tissue ◽  
Polycystic Ovary ◽  
Mrna Abundance ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Subcutaneous Adipose

Objective Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

scholarly journals MRNA Expression of Adipocytokines and Glucose Transporter Type 4 (GLUT4) in Adipose Tissue in Women With and Without Polycystic Ovary Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A742-A743
Author(s):  
Katarzyna Maria Ozga ◽  
Magdalena Krzyczkowska Sendrakowska ◽  
Tomasz Milewicz ◽  
Marek Sanak ◽  
Robert Jach
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Serum Amyloid ◽  
Control Group ◽  
Ovary Syndrome ◽  
Glut 4 ◽  
Serum Amyloid A1

Abstract Background: The main feature of polycystic ovary syndrome (PCOS) is hyperandrogenism, adipocytes hypertrophy and chronic low-grade inflammation. It is known that PCOS is closely linked to functional dysfunction in adipose tissue, which in turn are connected with metabolic disturbances such as insulin resistance. However, there is no complete characterization of the adipose tissue in women with PCOS. Aim: To compare the expression of adipocytokines between women with and without PCOS. Materials and Methods: The total number of twenty two participants were enrolled into the study. Study group included ten women with PCOS diagnosed according to the Rotterdam criteria, the control group- twelve women without PCOS. Approximately 3 g of tissue was excised from subcutaneous adipose tissue through a small incision in the suprapubic area. mRNA was isolated and gene expression profiling was performed including following genes: GLUT4, irisin, leptin, omentin, vaspin, adiponectin, visfastin, apelin, serum amyloid A1 and chemerin. Blood samples were taken between 3rd and 5th day of the menstrual cycle to evaluate serum hormonal levels. The oral glucose tolerance test (OGTT) was done simultaneously with the assessment of glucose and insulin plasma levels at 0, 60 and 120 minute. Results: Patients with PCOS presents different mRNA expression of adipocytokines compared with control group. There were statistically significant differences in irisin, leptin, omentin, visfastin, chemerin and serum amyloid A1 expression, that were higher in PCOS. GLUT-4 and adiponectin expression was significantly lower in PCOS patient compared to control. Due to an insufficient measurement of apelin and vaspin gene expression there were not included in following analysis. Conclusions: mRNA expression of adipocytokines in adipose tissue in women with and without polycystic ovary syndrome is different. In women with PCOS, there is a higher expression of genes for most of adipocytokines with lower for adiponectin and GLUT-4.

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