scholarly journals Low-dose Bisphenol-A regulates inflammatory cytokines through GPR30 in mammary adipose cells

2019 ◽  
Vol 63 (4) ◽  
pp. 273-283 ◽  
Author(s):  
Ilaria Cimmino ◽  
Francesco Oriente ◽  
Vittoria D’Esposito ◽  
Domenico Liguoro ◽  
Pasquale Liguoro ◽  
...  

The dramatic rise in obesity and metabolic syndrome can be related, at least in part, to environmental chemical factors such as Bisphenol-A (BPA). In this study, we aimed to understand the effects of low-dose Bisphenol-A on the human mature adipocytes and stromal vascular fraction (SVF) cells, obtained from subcutaneous mammary adipose tissue of overweight female patients, undergoing surgical mammary reduction. 24 and/or 48-h exposure to BPA 0.1 nM elicited significant increase of the inflammatory molecules interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemo-attractant protein 1α (MCP1α) and induced G protein-coupled estrogen receptor 30 (GPR30) levels more than two-fold both in mature adipocytes and SVF cells. These effects were similar to that obtained in the presence of GPR30-specific agonist G1 (100 nM) and were reverted by G15 (1 µM), a GPR30-selective antagonist. As a result of BPA-GPR30 signaling activation, fatty acid synthase (FAS) and leptin mRNA levels were significantly higher upon BPA exposure (P < 0.05) in mature adipocytes, with an opposite effect on adiponectin (ADIPOQ). In addition, an increase in SVF cell proliferation and ERK1/2 phosphorylation, was observed, compared to untreated cells. G15 reverted all of these effects. Interestingly, the action of BPA on SVF cell growth was mimicked by IL-8 treatment and was reverted by incubation with anti-IL8 antibodies. All these data suggest that BPA at 0.1 nM, a ten times lower concentration than environmental exposure, increases the expression of pro-inflammatory cytokines via GPR30 both in mature mammary adipocytes and in SVF cells with a possible involvement of IL-8.

2013 ◽  
Vol 220 (3) ◽  
pp. 207-218 ◽  
Author(s):  
Emily Panagiotidou ◽  
Sophia Zerva ◽  
Dimitra J Mitsiou ◽  
Michael N Alexis ◽  
Efthymia Kitraki

Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life exposures to low doses of BPA exert long-lasting effects on animals' reproductive and brain physiology. However, little is known about the effects of BPA on the stress–response system. Given the interaction of sex and stress hormones, we examined the effect of a low perinatal BPA exposure on the function of the hypothalamic–pituitary–adrenal (HPA) axis at rest and upon application of acute stress. Throughout pregnancy and lactation rats received daily 40 μg BPA/kg body weight orally via cornflakes. We studied the effect of this low but chronic exposure to BPA in the male and female offspring at puberty. BPA exposure led to abnormal adrenal histology including reduced zona reticularis especially in male offspring, hyperplasia of zona fasciculata in both sexes, and increased adrenal weight in female offspring. BPA-treated females had increased basal corticosterone and reduced hypothalamic glucocorticoid receptors (GR) levels. Stressed BPA-exposed females exhibited anxiety-like behavioral coping, a less rigorous corticosterone response, and did not downregulate GR in the hypothalamus, compared with control females. BPA-exposed males exhibited a heightened corticosterone stress response compared with females; they also displayed increased pro-opiomelanocortin mRNA levels and retained the prestress levels of pituitary corticotropin-releasing hormone-receptor 1, compared with control males. We found that perinatal chronic exposure to a low dose of BPA perturbs the basal and stress-induced activity of the HPA axis in a sexually dimorphic manner at adolescence. Exposure to BPA might contribute to increased susceptibility to stress-related disorders in later life.


Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.


2000 ◽  
Vol 279 (6) ◽  
pp. R2329-R2335 ◽  
Author(s):  
Paul Trayhurn ◽  
Jacqueline S. Duncan ◽  
Anne M. Wood ◽  
John H. Beattie

White adipose tissue (WAT) has been examined to determine whether the gene encoding metallothionein (MT), a low-molecular-weight stress response protein, is expressed in the tissue and whether MT may be a secretory product of adipocytes. The MT-1 gene was expressed in epididymal WAT, with MT-1 mRNA levels being similar in lean and obese ( ob/ ob) mice. MT-1 mRNA was found in each of the main adipose tissue sites (epididymal, perirenal, omental, subcutaneous), and there was no major difference between depots. Separation of adipocytes from the stromal-vascular fraction of WAT indicated that the MT gene (MT-1 and MT-2) was expressed in adipocytes themselves. Treatment of mice with zinc had no effect on MT-1 mRNA levels in WAT, despite strong induction of MT-1 expression in the liver. MT-1 gene expression in WAT was also unaltered by fasting or norepinephrine. However, administration of a β3-adrenoceptor agonist, BRL-35153A, led to a significant increase in MT-1 mRNA. On differentiation of fibroblastic preadipocytes to adipocytes in primary culture, MT was detected in the medium, suggesting that the protein may be secreted from WAT. It is concluded that WAT may be a significant site of MT production; within adipocytes, MT could play an antioxidant role in protecting fatty acids from damage.


2012 ◽  
Vol 211 ◽  
pp. S159
Author(s):  
Sofiane Boudalia ◽  
Raymond Berges ◽  
Franck Menetrier ◽  
Cécile Helies ◽  
Marie-Chantal Canivenc-Lavier

2017 ◽  
Vol 118 (8) ◽  
pp. 570-579 ◽  
Author(s):  
Guang-Hui Chen ◽  
Christer Hogstrand ◽  
Zhi Luo ◽  
Dian-Guang Zhang ◽  
Shi-Cheng Ling ◽  
...  

AbstractThe present study explored the mechanisms of dietary Zn influencing Zn and lipid deposition in the fore- and mid- intestine in yellow catfishPelteobagrus fulvidraco, and investigated whether the mechanism was intestinal-region dependent. For this purpose, yellow catfish were fed three diets containing Zn levels of 8·83, 19·20 and 146·65 mg Zn/kg, respectively. Growth performance, intestinal TAG and Zn contents as well as activities and mRNA expression of enzymes and genes involved in Zn transport and lipid metabolism in the fore- and mid-intestine were analysed. Dietary Zn increased Zn accumulation as well as activities of Cu-, Zn-superoxide dismutase and ATPase in the fore- and mid-intestine. In the fore-intestine, dietary Zn up-regulated mRNA levels of ZnT1, ZnT5, ZnT7, metallothionein (MT) and metal response element-binding transcription factor-1 (MTF-1), but down-regulated mRNA levels of ZIP4 and ZIP5. In the mid-intestine, dietary Zn up-regulated mRNA levels of ZnT1, ZnT5, ZnT7, MT and MTF-1, but down-regulated mRNA levels of ZIP4 and ZIP5. Dietary Zn reduced TAG content, down-regulated activities of 6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and fatty acid synthase (FAS) activities, and reduced mRNA levels of 6PGD, G6PD, FAS, PPARγand sterol-regulator element-binding protein (SREBP-1), but up-regulated mRNA levels of carnitine palmitoyltransferase IA, hormone-sensitive lipase (HSLa), adipose TAG lipase (ATGL) and PPARαin the fore-intestine. In the mid-intestine, dietary Zn reduced TAG content, activities of G6PD, ME, isocitrate dehydrogenase and FAS, down-regulated mRNA levels of 6PGD, G6PD, FAS, acetyl-CoA carboxylase a, PPARγand SREBP-1, but up-regulated mRNA expression of HSLa, ATGL and PPARγ. The reduction in TAG content following Zn addition was attributable to reduced lipogenesis and increased lipolysis, and similar regulatory mechanisms were observed between the fore- and mid-intestine.


2002 ◽  
Vol 16 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Shizuka Honma ◽  
Atsuko Suzuki ◽  
David L. Buchanan ◽  
Yoshinao Katsu ◽  
Hajime Watanabe ◽  
...  

Author(s):  
Xin Dai ◽  
Xiao-Feng Sun ◽  
Ai-Qin Wang ◽  
Wanhong Wei ◽  
Sheng-Mei Yang

Gallic acid (GA), a phenol that is present in various plants, potentially contains antioxidant properties. This study aimed to investigate the effects of GA on the reproduction of adolescent male Brandt’s voles (Lasiopodomys brandtii (Radde, 1861)). Antioxidant levels and apoptosis in the testis, as well as reproductive physiology, were evaluated in adolescent males treated with GA. The results showed that a low dose of GA enhanced relative epididymis weight and the sperm density in the epididymis, increased the mRNA levels of steroidogenic acute regulatory protein in the testis, and reduced the percentages of abnormal and dead sperm. In addition, a low dose of GA significantly increased the levels of superoxide dismutase, catalase, and glutathione peroxidase, and decreased the level of malondialdehyde in the testis, as well as the mRNA and protein levels of the apoptosis related gene, caspase-3. However, a high dose of GA sharply reduced the average diameter of the seminiferous tubules compared to a low dose. Collectively, these findings demonstrate that GA treatment during puberty affects the reproductive responses of male Brandt’s voles in a dose-dependent manner by regulating antioxidant levels and apoptosis.


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