Increased regulated on activation, normal T-cell expressed and secreted levels and cysteine–cysteine chemokine receptor 5 upregulation in omental adipose tissue and peripheral blood mononuclear cells are associated with testosterone level and insulin resistance in polycystic ovary syndrome

Juan, Chi Chang; Chen, Kuo Hu; Chen, Chien Wei; Ho, Chi Hong; Wang, Peng Hui; Chen, Harn Shen; Hwang, Jiann Loung; Lin, Yu Hung; Seow, Kok-Min

doi:10.1016/j.fertnstert.2021.05.093

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…Maraviroc, a CCR5 antagonist, reduces liver fibrosis and injury, chronic liver disease, and tumor burden in mice fed a hepatocarcinogenic diet [ 23 ]. Another recent study demonstrated that CCR5 expression in adipose tissue and peripheral blood mononuclear cells was significantly higher in women with PCOS compared with women in the control group [ 24 ]. CCR5 was also upregulated in the THP-1 cells after chronic exposure to testosterone [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…Another recent study demonstrated that CCR5 expression in adipose tissue and peripheral blood mononuclear cells was significantly higher in women with PCOS compared with women in the control group [ 24 ]. CCR5 was also upregulated in the THP-1 cells after chronic exposure to testosterone [ 24 ]. However, the relationship between CCR5 and PCOS is still inconclusive.…”

Section: Introductionmentioning

confidence: 99%

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Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

Seow

Liu

Chen

et al. 2021

IJMS

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Polycystic ovary syndrome (PCOS), which affects 5–10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine–cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

Seow

Liu

Chen

et al. 2021

IJMS

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“…41,42 CCL5 levels in the blood and visceral WAT have been shown to be elevated in letrozole-induced PCOS in mice and in PCOS patients. 43,44 Our previous study showed that T+WSD treatment or the consumption of WSD alone for 3 years was associated with elevated CRP levels in female rhesus macaques, 10 suggesting that longer treatment is necessary for inducing a systemic proinflammatory response in NHPs.…”

Section: Discussionmentioning

confidence: 99%

Western‐style diet in the presence of elevated circulating testosterone induces adipocyte hypertrophy without proinflammatory responses in rhesus macaques

Burwitz,

Yusova,

Robino

et al. 2023

American J Rep Immunol

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ProblemAnovulatory infertility is commonly associated with hyperandrogenemia (elevated testosterone, T), insulin resistance, obesity, and white adipose tissue (WAT) dysfunction associated with adipocyte hypertrophy. However, whether hyperandrogenemia and adipocyte hypertrophy per se induce a proinflammatory response is unknown.Method of studyYoung adult female rhesus macaques were exposed to an obesogenic Western‐style diet (WSD) in the presence of elevated circulating testosterone (T+WSD) or a low‐fat control diet with no exogenous T. Immune cells residing in visceral omental white adipose tissue (OM‐WAT), corpus luteum and the contralateral ovary, endometrium, lymph nodes, bone marrow, and peripheral blood mononuclear cells were characterized by flow cytometry during the luteal phase of the reproductive cycle.ResultsFollowing one year of treatment, T+WSD animals became more insulin‐resistant and exhibited increased body fat and adipocyte hypertrophy compared to controls. T+WSD treatment did not induce macrophage polarization toward a proinflammatory phenotype in the tissues examined. Additionally, T+WSD treatment did not affect TNFα production by bone marrow macrophages in response to toll‐like receptor agonists. While the major lymphoid subsets were not significantly affected by T+WSD treatment, we observed a significant reduction in the frequency of effector memory CD8+ T‐cells (Tem) in OM‐WAT, but not in other tissues. Notably, OM‐WAT Tem frequencies were negatively correlated with insulin resistance as assessed by the Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR).ConclusionThis study shows that short‐term T+WSD treatment induces weight gain, insulin resistance, and adipocyte hypertrophy, but does not have a significant effect on systemic and tissue‐resident proinflammatory markers, suggesting that adipocyte hypertrophy and mild hyperandrogenemia alone are not sufficient to induce a proinflammatory response.

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“…Visceral adiposity in hyperandrogenic women could be attributed to the involvement of androgens in pre-adipocyte differentiation, particularly in abdominal fat [162]. A recent report by Juan et al [163] on the elevated expression of C-C chemokine receptor type 5 (CCR5) in adipocytes and peripheral blood cells and its association with AE and hyperinsulinemia in PCOS patients points to the role of chronic inflammation in adipose tissue dysfunction and AE of PCOS, aiding to the augmented metabolic aberrations manifested in this most common disorder of female population. There is ample evidence that obesity intensifies androgen production, an event characteristic of the associated hyperinsulinemia, which also includes the involvement of the adipose-derived hormones called adipokines [154].…”

Section: Adipose Tissue Dysfunction and Sex Steroidsmentioning

confidence: 99%

Polycystic ovary syndrome and immune deregulation: what do hormones want to say?

Johnson

Laloraya

2022

Explor Immunol

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Polycystic ovary syndrome (PCOS) is one of the most frequently observed endocrinopathies among women of reproductive age that redound to subfertility. The specific etiology of this heterogenic syndrome remains ambiguous. Metabolic complications, hormonal imbalance, deregulation in the immune system and their interrelationship make PCOS more complex. Hyperandrogenism and chronic low-grade inflammation modulate each other and enhance the self-perpetuation of PCOS. Even though there are many literature studies on PCOS and immune deregulation, this review focuses on the endocrine-immune nexus and how the altered endocrine system is embroiled in the immunopathology of PCOS.

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Increased regulated on activation, normal T-cell expressed and secreted levels and cysteine–cysteine chemokine receptor 5 upregulation in omental adipose tissue and peripheral blood mononuclear cells are associated with testosterone level and insulin resistance in polycystic ovary syndrome

Cited by 12 publications

References 32 publications

Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

Western‐style diet in the presence of elevated circulating testosterone induces adipocyte hypertrophy without proinflammatory responses in rhesus macaques

Polycystic ovary syndrome and immune deregulation: what do hormones want to say?

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