Adiponectin and resistin: potential metabolic signals affecting hypothalamo-pituitary gonadal axis in females and males of different species

Rak, Agnieszka; Mellouk, Namya; Froment, Pascal; Dupont, Joëlle

doi:10.1530/rep-17-0002

Cited by 85 publications

(89 citation statements)

References 84 publications

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“…Ongoing research revealed that adipocyte dysfunction is pivotal in the pathogenesis of PCOS, with deranged release of adipokines, such as adiponectin and leptin . In the present study, and for the first time, we evaluated the serum levels of CTRP6 in females diagnosed with PCOS.…”

Section: Discussionmentioning

confidence: 82%

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

et al. 2020

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

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Section: Discussionmentioning

confidence: 82%

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

et al. 2020

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“…Currently, the data have been obtained on the relationship between the male reproductive system and the levels and functional activity of the adipokines, such as leptin, adiponectin, resistin, and visfatin (Elekofehinti, Ejelonu, Kamdem, Akinlosotu, & Adanlawo, 2017; Elfassy et al, 2018; Estienne et al, 2019). Although the adipokines are synthesized and secreted by the adipose tissue, the expression of adipokines and components of their signaling cascades is shown in the testes (Gurusubramanian & Roy, 2014; Rak, Mellouk, Froment, & Dupont, 2017). The plasma levels of adipokines change dramatically not only in DM2, as a result of obesity and impaired energy metabolism, but also in DM1 due to acute hyperglycemia, reduced insulin signaling and the activation of inflammation and oxidative stress (Perry, 2017; Yazıcı et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Effect of metformin on testicular expression and localization of leptin receptor and levels of leptin in the diabetic mice

Annie

Jeremy

Gurusubramanian

et al. 2020

Molecular Reproduction Devel

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Diabetes mellitus impairs testicular activity and leads to infertility. Leptin is one of the endogenous regulators of the male reproductive functions, but the role of leptin and its receptor (LEPR/Ob-R) in the control of testosterone production and testicular proliferation has not been investigated so far, especially in the Type 1 diabetes mellitus (DM1). Metformin is an anti-hyperglycemic drug which is beneficial for treating the both DM2 and DM1. The aim of this work was to study the possible role of leptin and Ob-R in the regulation of steroidogenesis and proliferation in the testes of mice with streptozotocin-induced DM1 (75 mg/kg/day, 4 days) and to estimate the restoring effect of metformin treatment (500 mg/kg, 2 weeks) on the diabetic testes. In the diabetic testes, the plasma and intratesticular leptin levels and plasma testosterone levels were reduced and completely restored by metformin treatment. Metformin also restored the expression of the steroidogenic transport protein steroidogenic acute regulatory protein reduced in DM1. In the diabetic testes, the expression of Ob-R was downregulated and the immunolocalization of Ob-R showed weak staining in the Leydig cells, the primary spermatocytes and the round spermatids. The germ cell proliferation was also reduced in DM1, as noticed with proliferating cell nuclear antigen (PCNA) expression. Metformin increased the Ob-R expression and immunostaining in the different cell types and improved the PCNA expression. Thus, DM1 impairs the testicular steroidogenesis and proliferation by inhibiting the leptin signaling, causing a decrease in leptin levels and Ob-R expression in the testes of diabetic mice, while metformin improves the leptin signaling and restores testosterone production and testicular proliferation. K E Y W O R D S diabetes mellitus, leptin, metformin, Ob-R, testes, testosterone 1 | INTRODUCTION The Types 1 and 2 diabetes mellitus (DM1 and DM2) are widespread metabolic diseases. The DM1 is characterized by insulin deficiency and severe hyperglycemia, while the DM2 is characterized by insulin resistance and impaired glucose tolerance (American Diabetes Association, 2013). In DM, the prolonged hyperglycemia, the pathological changes in energy metabolism and

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“…Although adiponectin may be integrated into a complex intracellular communication system that regulates specific cell functions (Rak et al, ), there is no information about the molecular mechanisms by which adiponectin promotes oocyte maturation in goats. Therefore, the aim of this study was to investigate whether (a) the addition of adiponectin during maturation of goat oocytes affects meiotic progression; (b) the beneficial effect of adiponectin on oocyte function is mediated by the MAPK MEK1/2 pathway; and (c) adiponectin differentially affects the mRNA abundance of genes relevant for adiponectin signal transduction in oocytes.…”

Section: Introductionmentioning

confidence: 99%

“…Adiponectin is a 30-kDa protein hormone predominantly produced by adipose tissue and abundant in the circulation (1-50 μg/ ml) of mammals (Maillard et al, 2010;Rak, Mellouk, Froment, & Dupont, 2017). The circulating levels of adiponectin are inversely correlated with body fat mass and positively associated with lipid metabolism, glucose homeostasis and insulin sensitivity (De Koster et al, 2016;Yamauchi et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…The circulating levels of adiponectin are inversely correlated with body fat mass and positively associated with lipid metabolism, glucose homeostasis and insulin sensitivity (De Koster et al, 2016;Yamauchi et al, 2001). In addition to its role in regulating energy homeostasis, adiponectin has been implicated in the control of reproductive functions of several species (Campos, Palin, Bordignon, & Murphy, 2008;Palin, Bordignon, & Murphy, 2012;Rak et al, 2017). There is accumulating evidence that adiponectin plays a role in the cascade of events associated with oocyte maturation.…”

Section: Introductionmentioning

confidence: 99%

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Effects of adiponectin during in vitro maturation of goat oocytes: MEK 1/2 pathway and gene expression pattern

Gomes

Costa

Silva

et al. 2018

Reprod Domestic Animals

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Recent studies have shown that adiponectin, an adipokine predominantly produced by adipose tissue, regulates several reproductive processes. However, the mechanisms of action of adiponectin on the maturation of goat oocytes remain to be determined. The aim of this study was to investigate whether (a) adiponectin influences the meiotic maturation of goat oocytes; (b) MAPK MEK 1/2 mediates the effects of adiponectin; and 3) adiponectin differentially affects mRNA relative abundance of genes relevant for adiponectin signal transduction in goat oocytes. The addition of adiponectin (5 μg/ml) during the maturation of goat oocytes resulted in a higher percentage of successful nuclear maturation compared to those of the group without adiponectin (p < 0.05). Adiponectin-stimulated nuclear oocyte maturation was significantly impaired by a mitogen-activated protein kinase MEK 1/2 inhibitor, U0126 (p < 0.05). There was no evidence of any adiponectin-induced difference in the relative transcript abundances of AdipoR1, AdipoR2, AMPKα1, AMPKα2, PPARα and PPARγ genes. In conclusion, these results indicate that adiponectin has a positive effect on the meiotic maturation of goat oocytes through the MAPK MEK 1/2 pathway. Furthermore, the adiponectin does not affect the relative abundance of genes relevant for adiponectin signal transduction in goat oocytes.

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Adiponectin and resistin: potential metabolic signals affecting hypothalamo-pituitary gonadal axis in females and males of different species

Cited by 85 publications

References 84 publications

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

Effect of metformin on testicular expression and localization of leptin receptor and levels of leptin in the diabetic mice

Effects of adiponectin during in vitro maturation of goat oocytes: MEK 1/2 pathway and gene expression pattern

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