Eicosapentaenoic Acid Improves Polycystic Ovary Syndrome in Rats via Sterol Regulatory Element-Binding Protein 1 (SREBP-1)/Toll-Like Receptor 4 (TLR4) Pathway

Wang, Yanting; He, Jinying; Yang, Jing

doi:10.12659/msm.909098

Cited by 21 publications

(12 citation statements)

References 30 publications

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“…We showed that BBR regulated the expression levels of TLR4 , LYN , NF-kB , TNF-α , IL-1 , and IL-6 caused by PCOS. TLR4 plays an important role in proinflammatory signaling and its levels are significantly higher in rats with PCOS compared to those without PCOS [ 28 ]. Further, TLR4 binds to its receptor and activates NF-kB to produce proinflammatory cytokines, including TNF-α , IL-1 , and IL-6 [ 11 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis

Shen

2021

Reprod Biol Endocrinol

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Background Polycystic ovary syndrome (PCOS) is a common endocrine disease of the female reproductive system that seriously affects women’s health. Berberine (BBR) has many pharmacological properties and is used as an insulin sensitizer. This study aimed to investigate the effect of BBR on PCOS and explore its related mechanisms. Methods Forty-two rats were randomly divided into the following six groups (n = 7 per group): control, control + BBR, PCOS-normal diet (ND), PCOS-ND + BBR, PCOS-high-fat diet (HFD), and PCOS-HFD + BBR. The PCOS rat models were established by injecting rats with dehydroepiandrosterone. Further, the rats were gavaged with BBR (150 mg/kg/d) for 6 weeks. Then, the body weight, HOMA-IR, and testosterone levels of all rats were determined. Cell apoptosis of ovary granulosa cells was determined by a TUNEL assay kit. Real-time quantification PCR (RT-qPCR) and western blotting were utilized to evaluate the expression of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3. Results BBR reduced the levels of insulin resistance and testosterone in PCOS rats. Additionally, the cell apoptosis rate increased significantly in PCOS rats (P < 0.05) and decreased after BBR treatment (P < 0.05). The results of RT-qPCR and western blotting showed that the expression levels of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3 significantly increased in PCOS rats, while BBR suppressed their expression levels. Conclusions BBR may relieve PCOS pathology and IR values by inhibiting cell apoptosis and by regulating the expression levels of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3.

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Section: Discussionmentioning

confidence: 99%

Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis

Shen

2021

Reprod Biol Endocrinol

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“…A study indicates that an intake of dietary EPA exerted beneficial effects on androgens in PCOS (62). Moreover, EPA treatment increases the number of follicular cell layers and decreased the levels of LH and T in PCOS (27).…”

Section: Discussionmentioning

confidence: 99%

“…Dietary ALA-rich FO inhibited the production of TNF-α, IL-1β, and IL-6 in T2DM and ALD (37,38). EPA treatment can decrease IL-1β and TNF-α but increase IL-10 in PCOS (27). Clinical studies have shown that the supplementation of omega-3 PUFAs is beneficial in decreasing the MCP-1 expression in macrophages and the levels of endothelial chemokine (72,73).…”

Section: Discussionmentioning

confidence: 99%

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Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats

Wang

Sha

et al. 2020

Front. Endocrinol.

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Polycystic ovary syndrome (PCOS) represents a common endocrine-metabolic disorder disease with chronic low-grade inflammation and alteration of intestinal flora. Serving as functional food, flaxseed oil (FO), which is rich in plant-derived α-linolenic acid of omega-3 polyunsaturated fatty acids, has been proven to benefit for chronic metabolic diseases. However, the exact role of dietary FO on PCOS remains largely unclear. In the present study, 6-week-old female Sprague-Dawley rats were randomly divided into four groups (eight rats/group), including (a) pair-fed (PF) control (CON) group (PF/CON), (b) FO-fed CON group (FO/CON), (c) PF with letrozole-induced PCOS model (MOD) group (PF/MOD), and (d) FO-fed MOD group (FO/MOD). All rats were fed a standard diet. After 3 weeks of modeling and subsequent 8 weeks of treatment, the rats in diverse groups were euthanized and associated indications were investigated. The results showed that dietary FO ameliorated the disorder of estrous cycle and ovarian morphology. In parallel, dietary FO improved the sex steroid hormone disturbance (luteinizing hormone/follicle-stimulating hormone, estrogen, testosterone, and progesterone), body weights, dyslipidemia, and insulin resistance. Moreover, FO treatment improved plasma and ovary inflammatory interleukin (IL)-1β, IL-6, IL-10, and IL-17A, tumor necrosis factor-α, and monocyte chemoattractant protein-1. Additionally, FO intervention significantly modulated the composition of gut microbiota and vaginal microbiota by increasing the abundances of Allobaculum, Lactobacillus, Butyrivibrio, Desulfovibrio, Bifidobacterium, Faecalibacterium, Parabacteroides as well as decreasing the abundances of Actinobacteria, Bacteroides, Proteobacteria, and Streptococcus, the ratio of Firmicutes/Bacteroidetes. A decrease in plasma lipopolysaccharide level and an increase in short-chain fatty acids, including acetic acid, propionic acid, butyric acid and pentanoic acid, were determined after dietary FO supplementation. Correlation analysis Wang et al. FO Ameliorates PCOS in Rats revealed close relationships among sex steroid hormones, inflammation, and gut/vaginal microbiota. Collectively, this study demonstrated that dietary FO ameliorated PCOS through the sex steroid hormones-microbiota-inflammation axis in rats, which may contribute to the understanding of pathogenesis and potentially serve as an inexpensive intervention in the control of PCOS.

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“…However, the literature regarding TLR expression in patients with PCOS is scarce. Two studies presented data describing increased TLR4 in ovarian tissues from animal models of PCOS [54,55], and it has been reported that ovarian cumulus cells from women with PCOS presented an abnormal TLR expression [56]. Gonzalez et al [57,58] recently reported increased TLR2 expression in peripheral blood mononuclear cells in women with PCOS after ingestion of cream regardless of obesity, and a similar increase in TLR4 expression that occurred mostly in obese women with the syndrome.…”

Section: Discussionmentioning

confidence: 99%

TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones

et al. 2020

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We studied if macronutrients of the diet have different effects on leukocyte activation, and if these effects are influenced by sex hormones or obesity. We analyzed leukocyte cell surface and gene expression of toll-like receptors 2 and 4 (TLR2 and TLR4) during fasting and after macronutrient loads in women with polycystic ovary syndrome and female and male controls. Fasting TLR2 surface expression in neutrophils was higher in men than in women. Obese subjects presented higher TLR2 gene expression than nonobese individuals, particularly in men. In contrast, surface TLR4 expression was lower in men and in obese individuals. Postprandial cell-surface expression decreased similarly after all macronutrient loads. Neutrophil TLR2 decreased only in obese subjects whereas TLR4 showed a greater decrease in nonobese individuals. However, TLR2 gene expression increased after glucose ingestion and decreased during the lipid load, while TLR4 was induced in response to lipids and mostly to glucose. Postprandial TLR gene expression was not influenced by group of subjects or obesity. Both cell-surface and gene postprandial expression inversely correlated with their fasting levels. These responses suggest a transient compensatory response aiming to prevent postprandial inflammation. However, obesity and sex hormones showed opposite influences on surface expression of TLR2 and TLR4, but not on their gene expression, pointing to regulatory posttranscriptional mechanisms.

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Eicosapentaenoic Acid Improves Polycystic Ovary Syndrome in Rats via Sterol Regulatory Element-Binding Protein 1 (SREBP-1)/Toll-Like Receptor 4 (TLR4) Pathway

Cited by 21 publications

References 30 publications

Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis

Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis

Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats

TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones

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