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 ◽  
...  

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.

Author(s):  
Soulmaz Shorakae ◽  
Eveline Jona ◽  
Courten Barbora de ◽  
Gavin Lambert ◽  
Elisabeth Lambert ◽  
...  

Author(s):  
Soulmaz Shorakae ◽  
Eveline Jona ◽  
Barbora de Courten ◽  
Gavin W. Lambert ◽  
Elisabeth A. Lambert ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongcai Ye ◽  
Chunlong Yan ◽  
Huiqiao Zhou ◽  
Yuanyuan Huang ◽  
Meng Dong ◽  
...  

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.


2019 ◽  
Vol 181 (5) ◽  
pp. 473-480 ◽  
Author(s):  
Oliveira Flávia R ◽  
Marcelo Mamede ◽  
Mariana F Bizzi ◽  
Rocha Ana Luiza L ◽  
Cláudia N Ferreira ◽  
...  

Objective To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9–15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7–18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman’s r = −0.630, P = 0.000) and waist circumference (r = −0.592, P = 0.000) but not with plasma irisin levels. Conclusions BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.


2017 ◽  
Vol 47 ◽  
pp. 21-28 ◽  
Author(s):  
Tao Hu ◽  
Xiaoxue Yuan ◽  
Rongcai Ye ◽  
Huiqiao Zhou ◽  
Jun Lin ◽  
...  

2019 ◽  
Vol 112 (3) ◽  
pp. e387-e388
Author(s):  
Flavia R. Oliveira ◽  
Marcelo Mamede ◽  
Mariana F. Bizzi ◽  
Ana Luiza L Rocha ◽  
Claudia N. Ferreira ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A742-A743
Author(s):  
Katarzyna Maria Ozga ◽  
Magdalena Krzyczkowska Sendrakowska ◽  
Tomasz Milewicz ◽  
Marek Sanak ◽  
Robert Jach

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.


Sign in / Sign up

Export Citation Format

Share Document