scholarly journals Altered vitamin D3 metabolism in the ovary and periovarian adipose tissue of rats with letrozole-induced PCOS

2020 ◽  
Vol 155 (1) ◽  
pp. 101-116
Author(s):  
Malgorzata Grzesiak ◽  
Gabriela Burzawa ◽  
Patrycja Kurowska ◽  
Klaudia Blaszczyk ◽  
Agata Szlaga ◽  
...  

AbstractVitamin D3 (VD3) plays an important role in the ovary and its deficiency is associated with ovarian pathologies, including polycystic ovary syndrome (PCOS). However, there is no data related to VD3 metabolism in the ovary during PCOS. Herein, we investigated differences in the expression of VD3 receptor (VDR) and key VD3 metabolic enzymes, 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1), in the ovary and periovarian adipose tissue (POAT) of control (proestrus and diestrus) and PCOS induced by letrozole rats. Vdr, Cyp27b1 and Cyp24a1 mRNA expression was determined, their protein abundance was examined and immunolocalized. Furthermore, VD3 metabolite concentrations in plasma (25OHD) and tissues (ovary and POAT; 1,25(OH)2D3), and plasma calcium level were determined. 25OHD concentration decreased markedly in letrozole-treated rats in comparison with controls, whereas calcium concentration did not vary among the examined groups. The amount of 1,25(OH)2D3 decreased in both ovary and POAT of PCOS rats. In the ovary, we found decreased Cyp27b1 and increased Vdr mRNA expression in letrozole-treated and diestrus control group. Corresponding protein abundances were down-regulated and up-regulated, respectively but only following letrozole treatment. In POAT, only Cyp27b1 transcript level and CYP27B1 protein abundance were decreased in letrozole-treated rats. VDR was immunolocalized in healthy and cystic follicles, while CYP27B1 and CYP24A1 were found exclusively in healthy ones. Concluding, our results provide the first evidence of disrupted VD3 metabolism in the ovary and POAT of PCOS rats. The reduced 1,25(OH)2D3 concentration in those tissues suggests their contribution to VD3 deficiency observed in PCOS and might implicate in PCOS pathogenesis.

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.


2013 ◽  
Vol 219 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Bee K Tan ◽  
Jing Chen ◽  
Raghu Adya ◽  
Manjunath Ramanjaneya ◽  
Vanlata Patel ◽  
...  

Adipolin is a novel adipokine with anti-inflammatory and glucose-lowering properties. Lower levels of adipolin are found in obese and diabetic mice. Polycystic ovary syndrome (PCOS) is a pro-inflammatory state associated with obesity and diabetes. To date, there are no human studies on adipolin. Therefore, we measured serum (ELISA) and adipose tissue adipolin mRNA expression (RT-PCR) and protein concentrations (western blotting) in PCOS and control subjects. We also investigated the ex vivo effect of glucose and metformin on adipolin protein production in human subcutaneous adipose tissue explants. We report novel data that serum and subcutaneous adipose tissue adipolin mRNA expression and protein concentrations were significantly lower in women with PCOS compared with control subjects. Furthermore, Spearman's rank analysis showed that serum adipolin concentrations were significantly negatively correlated with BMI, waist-to-hip ratio, and glucose (P<0.05). However, when subjected to multiple regression analysis, none of these variables were predictive of serum adipolin concentrations (P>0.05). Also, subcutaneous adipose tissue adipolin mRNA expression and protein concentrations were only significantly negatively correlated with glucose (P<0.05). No significant correlations were found with omental adipose tissue adipolin mRNA expression and protein concentrations (P>0.05). Moreover, glucose profoundly reduced and metformin significantly increased adipolin protein production in human adipose tissue explants respectively. Importantly, metformin's effects appear to be via the AMP-activated protein kinase signaling pathway.


2007 ◽  
Vol 292 (1) ◽  
pp. E24-E31 ◽  
Author(s):  
Lone Frydelund-Larsen ◽  
Thorbjorn Akerstrom ◽  
Søren Nielsen ◽  
Pernille Keller ◽  
Charlotte Keller ◽  
...  

Visfatin [pre-β-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of V̇o2 max or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4.5, and 6 h in response to exercise ( n = 8) compared with preexercise samples and compared with the resting control group ( n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied by elevated levels of plasma visfatin. Recombinant human IL-6 infusion to mimic the exercise-induced IL-6 response ( n = 6) had no effect on visfatin mRNA expression in adipose tissue compared with the effect of placebo infusion ( n = 6). The finding that exercise enhances subcutaneous adipose tissue visfatin mRNA expression suggests that visfatin has a local metabolic role in the recovery period following exercise.


2021 ◽  
Vol 18 (3) ◽  
pp. 0480
Author(s):  
Seyyed Amir Yasin Ahmadi ◽  
Mandana Beigi Boroujeni ◽  
Naser Pajouhi ◽  
Amin Hasanvand ◽  
Afshin Hasanvand ◽  
...  

There are many animal models for polycystic ovary (PCO); using exogenous testosterone enanthate is one of the methods of induction of these models. However, induction of insulin resistance should also be studied in the modeling technics. Therefore, the present study aims to investigate the expression of insulin receptor substrate (Irs)-2 mRNA in the liver tissue of rat PCO model. Nineteen Wistar rats were divided into three groups; (1) PCO modeling group (N =7) received daily 1.0 mg/100g testosterone enanthate solved in olive oil along with free access dextrose water 5%, (2) vehicle group (N =6), which handled like the PCO group, but did not receive testosterone enanthate, (3) control group (N =6) with standard care. All the animals were administered via intra-peritoneal injection for 14 days. Expression of Irs-2 mRNA was studied with real-time PCR and fold changes (FC) were reported. The average of expression in the control group was considered as the calibrator. About 13.4% expression reduction was found in the PCO group (FC =0.874, P-value =0.043). No significant reduction was found in the vehicle group (FC =0.951, P-value =0.076). However, analysis of variance did not show a significant difference between all the groups of study (P-value =0.085). The present model of PCO might induce insulin resistance at liver level with a low effect size via reduction in the mRNA expression of Irs-2. Study of the involved genes and molecules in other tissues of PCO animal models is suggested.


2021 ◽  
Author(s):  
Miao Lin ◽  
Maocheng Jiang ◽  
Tianyu Yang ◽  
Xiaoyu Ma ◽  
Guoqi Zhao ◽  
...  

Abstract BackgroundIn postpartum dairy cows, dry matter intake (DMI) was dramatically decreased, resulting in the decreased plasma glucose, a negative energy balance (NEB), and negative nutrient balance. Asprosin, which is a fasting-induced glucogenic protein hormone secreted by adipose tissue, promotes plasma glucose level. However, effect of asprosin on the hepatic glucose output in primary bovine hepatocytes and plasma asprosin level in postpartum dairy cows remain not reported. ResultsOur results demonstrated that fibrillin 1 (FBN1) showed much higher mRNA expression in mammary gland and adipose tissue compared with heart, liver, spleen, lung, and kidney. The recombinant bovine His-asprosin was not found in supernatant of E. coli lysate, but present in the inclusion bodies in E. coli. The bovine His-asprosin proteins were > 90 % pure by Coomassie Blue-stained SDS-PAGE gel analysis. Asprosin enhanced (P = 0.031) the mRNA expression of PCK2 in primary bovine hepatocyte compared with control group, and FBP1 tended (P = 0.086) to be upregulated in primary bovine hepatocyte treated by Asprosin. Remarkably, glucose output was increased (P = 0.03) in primary bovine hepatocytes exposed to asprosin than control group. In addition, Asprosin can promote PKA activity in primary bovine hepatocytes, but not AKT. Asprosin was observed to be present in bovine plasma at consistent nanomolar levels. The postpartum cows exhibited (P = 0.003) much higher level of circulating asprosin compared with mid-lactation dairy cows. ConclusionsThese findings indicate that asprosin should be further considered for use as a novel therapy strategy for NEB and negative nutrient balance in postpartum period.


2013 ◽  
Vol 4 (5) ◽  
pp. 421-429 ◽  
Author(s):  
S. Lie ◽  
J. A. Duffield ◽  
I. C. McMillen ◽  
J. L. Morrison ◽  
S. E. Ozanne ◽  
...  

Intrauterine growth restriction (IUGR) followed by accelerated growth after birth is associated with an increased risk of abdominal (visceral) obesity and insulin resistance in adult life. The aim of the present study was to determine the impact of IUGR on mRNA expression and protein abundance of insulin signaling molecules in one of the major visceral fat depots, the omental adipose depot. IUGR was induced by placental restriction, and samples of omental adipose tissue were collected from IUGR (n = 9, 5 males, 4 females) and Control (n = 14, 8 males, 6 females) neonatal lambs at 21 days of age. The mRNA expression of the insulin signaling molecules, AMP-kinase (AMPK) and adipogenic/lipogenic genes was determined by qRT-PCR, and protein abundance by Western Blotting. AMPKα2 mRNA expression was increased in male IUGR lambs (0.015 ± 0.002 v. 0.0075 ± 0.0009, P < 0.001). The proportion of the AMPK pool that was phosphorylated (%P-AMPK) was lower in IUGR lambs compared with Controls independent of sex (39 ± 9% v. 100 ± 18%, P < 0.001). The mRNA expression and protein abundance of insulin signaling proteins and adipogenic/lipogenic genes was not different between groups. Thus, IUGR is associated with sex-specific alterations in the mRNA expression of AMPKα2 and a reduction in the percentage of the total AMPK pool that is phosphorylated in the omental adipose tissue of neonatal lambs, before the onset of visceral obesity. These molecular changes would be expected to promote lipid accumulation in the omental adipose depot and may therefore contribute to the onset of visceral adiposity in IUGR animals later in life.


2017 ◽  
Vol 63 (6) ◽  
pp. 582-590 ◽  
Author(s):  
M.A. Vasilenko ◽  
E.V. Kirienkova ◽  
D.A. Skuratovskaya ◽  
P.A. Zatolokin ◽  
N.I. Mironyuk ◽  
...  

Chemerin is a mediator of adipose tissue involved in the regulation of many processes, including lipogenesis, and inflammatory response. The role of chemerin in the development of insulin resistance has been insufficiently studied and needs detailed understanding. The aim of the study was to investigate chemerin production in obese patients with different states of carbohydrate metabolism. The study included 155 patients with a diagnosis of obesity; 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors who did not have obesity. For comparison of the results of a study to determine the levels of tissue-specific mRNA expression of the genes IL-6, TNF-a, RARRES2, (encoding IL-6, TNF-a and chemerin) in adipose tissue introduced a control group 2 – 30 patients without obesity. Study on the relative level of mRNA expression of the genes IL-6, TNF-a and RARRES2 (encoding IL-6, TNF-a and chemerin) was carried out using real time PCR. Concentrations of IL-6, TNF-a, and chemerin were measured in serum/plasma using an enzyme-linked immunosorbent assay (ELISA). We found significant differences in the plasma level of chemerin and tissue-specific features of RARRES2 gene expression in obese patients, depending on the degree of obesity and the state of carbohydrate metabolism. Multidirectional associations of RARRES2 gene expression with TNF-a and IL-6 genes in adipose tissues of different localization are shown: in obese patients (BMI £40 kg/m2) without type 2 diabetes – negative, and type 2 diabetes – positive. Identified relationship chemerin plasma content and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, proinflammatory molecules indicate chemerin involved in metabolic and immune processes in obesity.


2008 ◽  
Vol 158 (6) ◽  
pp. 793-801 ◽  
Author(s):  
Mojca Jensterle ◽  
Andrej Janez ◽  
Barbara Mlinar ◽  
Janja Marc ◽  
Janez Prezelj ◽  
...  

ObjectiveThe insulin-resistant state of the polycystic ovary syndrome (PCOS) was found to be associated with a decreased glucose transporter GLUT4 expression in the insulin target tissues. This study was performed to explore whether the well-known clinical, hormonal and metabolic efficacy of metformin or rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA expression in patients with PCOS.MethodsWe enrolled 35 women with PCOS. They received either metformin or rosiglitazone for 6 months. A history, blood samples for the measurement of androgens and s.c. adipose tissue samples were taken at baseline and end point. Quantification of GLUT4 mRNA expression in adipose tissue was performed using real-time quantitative PCR. Homeostasis model assessment (HOMAIR) score calculation was applied as a measure for insulin resistance (IR).ResultsGLUT4 mRNA expression in adipose tissue increased significantly in both groups (P<0.001). The increase was more pronounced in the rosiglitazone group (P=0.040). There was a statistically significant improvement of HOMAIRin both groups (P=0.008). After treatment, frequencies of menstrual bleeding were significantly higher (P<0.001) and serum total testosterone levels significantly lower in both groups (P=0.001).ConclusionsA 6-month therapy with insulin sensitizers resulted in marked improvement in adipose tissue GLUT4 mRNA expression in PCOS patients, rosiglitazone being more effective when compared with metformin. The augmentation of the insulin signal transduction was accompanied by a significant improvement of HOMAIR, menstrual pattern and androgen profile.


2004 ◽  
Vol 183 (1) ◽  
pp. 121-131 ◽  
Author(s):  
A Mostyn ◽  
J C Litten ◽  
K S Perkins ◽  
M C Alves-Guerra ◽  
C Pecqueur ◽  
...  

The present study aimed to determine whether porcine genotype and/or postnatal age influenced mRNA abundance or protein expression of uncoupling protein (UCP)2 or 3 in subcutaneous adipose tissue (AT) and skeletal muscle (SM) and the extent to which these differences are associated with breed-specific discordance in endocrine and metabolic profiles. Piglets from commercial and Meishan litters were ranked according to birth weight. Tissue samples were obtained from the three median piglets from each litter on either day 0, 4, 7, 14 or 21 of neonatal life. UCP2 protein abundance in AT was similar between genotypes on the first day of life, but it was elevated at all subsequent postnatal ages (P<0.05) in AT of Meishan piglets. In contrast, UCP2 mRNA abundance was lower in Meishans up to 14 days of age. UCP2 mRNA expression was not correlated with protein abundance in either breed at any age. UCP3 mRNA in AT was similar between breeds up to day 7; thereafter, expression was higher (general linear model, P<0.05) in Meishan piglets. Conversely, UCP3 mRNA expression in SM was higher in commercial piglets after day 7. Colonic temperature remained lower in Meishan than commercial piglets throughout the study; this was most obvious in the immediate post-partum period when Meishan piglets had lower (P<0.05) plasma triiodothyronine. In conclusion, we have demonstrated that porcine genotype influences the expression and abundance of UCP2 and 3, an influence which may, in part, be due to the distinctive endocrine profiles associated with each genotype.


2014 ◽  
pp. S299-S308 ◽  
Author(s):  
P. TRACHTA ◽  
J. DRÁPALOVÁ ◽  
P. KAVÁLKOVÁ ◽  
V. TOUŠKOVÁ ◽  
A. CINKAJZLOVÁ ◽  
...  

The aim of our study was to explore the effects of regular aerobic exercise on anthropometric, biochemical and hormonal parameters and mRNA expression of selected factors involved in metabolic regulations in subcutaneous adipose tissue of patients with obesity. Fifteen obese women with arterial hypertension underwent a three-month exercise program consisting of 30 min of aerobic exercise 3 times a week. Fifteen healthy lean women with no intervention served as a control group. Obese group underwent anthropometric measurements, blood sampling, subcutaneous adipose tissue (SCAT) biopsy and 24-h blood pressure monitoring at baseline and after three months of exercise, while control group was examined only once. At baseline, obese group had increased SCAT expression of proinflammatory cytokines and adipokines relative to control group. Three months of regular exercise improved anthropometric parameters, decreased CRP, blood glucose and HOMA-IR, while having no significant effect on lipid profile and blood pressure. Gene expressions in SCAT were not affected by physical activity with the exception of increased aquaporin-3 mRNA expression. We conclude that three months of regular exercise decrease systemic subclinical inflammation with only minor influence on the blood pressure and the endocrine function of subcutaneous fat.


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