Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats

Lian, Yuling; Zhao, Fangui; Wang, Wenjun

doi:10.1016/j.bbrc.2016.05.117

Cited by 26 publications

(18 citation statements)

References 39 publications

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“…our previous study revealed central leptin resistance and low-grade chronic inflammation in the hypothalamus of PcoS rats (12). in the current study, the protein level of il-1β, il-6 and TnF-α, and the mrna expression of iKKβ, nF-κB and SOCS3 in the hypothalamus were significantly increased in Model group rats compared with the control group, which was consistent with our previous conclusions.…”

Section: Discussionsupporting

confidence: 93%

“…SocS3 has a crucial role in mediating the effects of hypothalamic iKKβ/nF-κB on leptin resistance (35,36). our previous study (12) demonstrated that central icv injection of leptin decreased 24 h food intake and body weight gain, and induced increasing expression of p-STaT3 in the hypothalamus of control group rats. However, central icv injection of leptin did not exert an effect on 24 h food intake, body weight, and p-STaT3 expression in rats of PcoS group, suggesting that central leptin resistance was present in the PcoS rats induced by letrozole.…”

Section: Discussionmentioning

confidence: 82%

“…However, central icv injection of leptin did not exert an effect on 24 h food intake, body weight, and p-STaT3 expression in rats of PcoS group, suggesting that central leptin resistance was present in the PcoS rats induced by letrozole. Furthermore, inflammatory markers were upregulated in the hypothalami of PcoS rats, indicating that there was a state of chronic low-grade inflammation in the hypothalamus, which may be the potential mechanism of central leptin resistance in PcoS rats (12). in the present study, BGc may have improved central leptin resistance of PcoS rats by decreasing the protein levels of il-6 and TnF-α, and the mrna expression of iKKβ, nF-κB and SocS3 in hypothalamus of PcoS rats, which may partially explain the therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

“…in addition, leptin, which was the first adipokine to be discovered, has a crucial role in maintaining food intake and energy balance, and regulates reproduction function (9)(10)(11). our previous study suggested that there was a state of chronic low-grade inflammation in the hypothalamus of PcoS model rats, which may account for central leptin resistance rats (12). The exact mechanism of PcoS remains unclear and requires further research.…”

Section: Introductionmentioning

confidence: 99%

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Use of Bao Gui capsule in treatment of a polycystic ovary syndrome rat model

2020

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The present study was designed to elucidate the underlying mechanisms of Bao Gui capsule (BGc) against hyperandrogenism, insulin resistance and leptin resistance of PcoS. letrozole was used to induce a PcoS model in rats, which were then randomly divided into four groups (n=9): control, Model, high-dose BGc (BGc-H) and low-dose BGc (BGc-l) group. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (lH), testosterone (T), estradiol (e 2 ), insulin, leptin, and interleukin (il)-1β, il-6 and tumor necrosis factor-α (TnF-α) in the hypothalamus were determined by eliSa. Protein levels of cytochrome P450c17α and cytochrome P450 aromatase (P450arom) in ovaries were determined by immunohistochemistry and western blot analysis. additionally, the expression of GluT4 in uterus and muscle tissue, and nF-κB, iKKβ and SocS3 mrna levels in the hypothalamus were evaluated. BGC significantly reduced body weight gain and decreased serum levels of lH/FSH, T, log T/e 2 , insulin and leptin compared with the PcoS model rats. Furthermore, BGc markedly reduced the expression of P450c17α and significantly increased the expression of P450arom in ovaries, and increased the expression of GluT4 in uterus and muscle tissues. BGc also effectively reduced the level of il-6 and TnF-α, and the expression of iKKβ, nF-κB and SocS3 in the hypothalamus of PcoS model rats. These results suggest that BGc may effectively improve hyperandrogenism, insulin resistance, endometrial receptivity and the low-grade chronic inflammation in the hypothalamus.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of Bao Gui capsule in treatment of a polycystic ovary syndrome rat model

2020

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“…an orexigenic factor, was increased, whereas that of 5HT2CR, an anorexigenic factor, tended to be decreased in the prenatally UN PCOS model rats, suggesting that these changes may contribute to increased FI and BW gain in this group. Recently, it was reported that central leptin resistance was observed in PCOS model rats, i.e., central injection of leptin could not reduce the FI and BW of letrozole-induced PCOS model rats (Lian et al 2016). Similarly, although the serum leptin level was increased in prenatally UN PCOS model rats, their gene expression levels of hypothalamic neuropeptide Y and OBRb remained unchanged, indicating that hypothalamic sensitivity for leptin might be decreased in this group.…”

Section: Effects Of Prenatal Undernutrition On the Metabolic Phenotypesmentioning

confidence: 91%

Prenatal undernutrition affects the phenotypes of PCOS model rats

Iwasa

Matsuzaki

Yano

et al. 2018

Journal of Endocrinology

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Although polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in women of reproductive age, its etiology remains poorly understood. From the perspective of developmental origins of health and disease, some studies have investigated the relationship between low birth weight and the prevalence of PCOS and/or PCOS phenotypes in humans; however, the results of these studies were inconclusive. Here, we evaluated the effects of prenatal undernutrition on the metabolic and reproductive phenotypes of dihydrotestosterone-induced PCOS model rats. The PCOS model rats showed increased body weight, food intake, fat weight, adipocyte size, and upregulation of inflammatory cytokines in adipose tissue; prenatal undernutrition exacerbated these metabolic changes. Prenatal undernutrition also increased the gene expression of hypothalamic orexigenic factor and decreased the gene expression of anorexigenic factor in the PCOS model rats. In addition, the PCOS model rats exhibited irregular cyclicity, polycystic ovaries, and disrupted gene expression of ovarian steroidogenic enzymes. Interestingly, prenatal undernutrition attenuated these reproductive changes in the PCOS model rats. Our results suggest that in dihydrotestosterone-induced PCOS model rats, prenatal undernutrition exacerbates the metabolic phenotypes, whereas it improves the reproductive phenotypes, and that such phenotypic changes may be induced by the alteration of some peripheral and central factors.

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