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

ABSTRACT: 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 ?-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)-1?, IL-6, IL-10, and IL-17A, tumor necrosis factor-?, 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 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.

SUBMITTER: Wang T

PROVIDER: S-EPMC7326049 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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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 Ting T Sha Liping L Li Yiwei Y Zhu Lili L Wang Zhen Z Li Ke K Lu Haixia H Bao Ting T Guo Li L Zhang Xiaoxia X Wang Hao H

Frontiers in endocrinology 20200527

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 ...[more]

PMID: 32670195

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Project description:The effects of docosahexaenoic acid supplements on cognitive function have long been demonstrated, but the effects of alpha-linolenic acid, a precursor of docosahexaenoic acid, have not been fully tested. The search for functional foods that delay cognitive decline in the older adults is considered a very important area from a preventive perspective. The aim of this study was to conduct an exploratory evaluation of alpha-linolenic acid on various cognitive functions in healthy older subjects. Sixty healthy older adults aged 65 to 80 years, living in Miyagi prefecture, without cognitive impairment or depression, were included in the randomized, double-blinded, placebo-controlled clinical trial. Study subjects were randomly divided into two groups and received either 3.7 g/day of flaxseed oil containing 2.2 g of alpha-linolenic acid, or an isocaloric placebo (corn oil) containing 0.04 g of alpha-linolenic acid for 12 weeks. The primary endpoints were six cognitive functions closely related to everyday life: attention and concentration, executive function, perceptual reasoning, working memory, processing speed and memory function. After 12 weeks of intake, changes in verbal fluency scores on the frontal assessment battery at bedside, a neuropsychological test assessing executive function, in which participants are asked to answer as many words as possible in Japanese, were significantly greater in the intervention group (0.30 ± 0.53) than in the control group (0.03 ± 0.49, p < 0.05). All other cognitive test scores were not significantly different between the groups. In conclusion, daily consumption of flaxseed oil containing 2.2 g alpha-linolenic acid improved cognitive function, specifically verbal fluency, despite the age-related decline, in healthy individuals with no cognitive abnormalities. Further validation studies focusing on the effects of alpha-linolenic acid on verbal fluency and executive function in older adults are needed, as verbal fluency is a predictor of Alzheimer's disease development, important for cognitive health.

Project description:BackgroundThe measurement of adrenal and ovarian androgens in women with PCOS has been difficult based on poor specificity and sensitivity of assays in the female range.MethodsWomen with PCOS (NIH criteria; n = 52) and control subjects with 25-35 day menstrual cycles, no evidence of hyperandrogenism and matched for BMI (n = 42) underwent morning blood sampling. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to simultaneously measure 13 steroids from a single blood sample to measure adrenal and ovarian steroids. Androgen and progesterone results were compared in the same samples using RIA.ResultsTestosterone, androstenedione, progesterone and 17OH progesterone levels were higher when measured using RIA compared to LC-MS/MS, although the testosterone RIA demonstrated the best agreement with the LC-MS/MS using a Bland-Altman analysis. Results using LC-MS/MS demonstrated that the concentration of androgens and their precursors were higher in women with PCOS than controls [median (2.5, 97.5th %ile); 1607 (638, 3085) vs. 1143 (511, 4784) ng/dL; p = 0.03]. Women with PCOS had higher testosterone [49 (16, 125) vs. 24 (10, 59) ng/dL], androstenedione [203 (98, 476) vs. 106 (69, 223) ng/dL] and 17OH progesterone levels [80 (17, 176) vs. 44 (17, 142) ng/dL] compared to controls (all P<0.02), but no differences in serum concentrations of the adrenal steroids DHEAS, cortisol, corticosterone and their 11 deoxy precursors. Women with PCOS also had an increase in the product:precursor ratio for 3β-hydroxysteroid dehydrogenase [22% (6, 92) vs. 20% (4, 43); p = 0.009].ConclusionLC-MS/MS was superior to RIA in measuring androstenedione, progesterone and 17OH progesterone levels, while testosterone measurements were better matched in the two assays. Androgen levels were higher in women with PCOS in the absence of a difference in adrenal-predominant steroids. These data support previous findings that the ovary is an important source for the androgen excess in women with PCOS.

Project description:Background Determination of the role of steroid hormones in expression and regulation of endometrial glucose transport 4 (GLUT4) in humans is important for understanding endometrial disorders such as polycystic ovary syndrome (PCOS), a common hormone-imbalance disease. Methods Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia and from PCOS patients with or without hyperplasia. In addition, endometrial tissues from postmenopausal women were incubated with human chorionic gonadotropin (hCG, 10 IU/ml), 17β-estradiol (E2, 10 nM), progesterone (P4, 100 nM), or a combination of E2 and P4 for 24 h. The expression of GLUT4 was measured at the mRNA level using quantitative real-time polymerase chain reaction (qRT-PCR) and at the protein level using Western blot analysis and immunohistochemistry. Results A cyclical change in GLUT4 expression pattern was observed in non-PCOS patients, and a high level of GLUT4 expression was seen in the proliferative phase compared to the secretory phase. Low levels of GLUT4 expression were found in PCOS patients compared to menstrual cycle phase-matched non-PCOS patients, and there was no significant change in GLUT4 expression in PCOS patients during the menstrual cycle. GLUT4 was localized in both epithelial and stromal cells, with notable changes in epithelial cells. We postulate that decreased GLUT4 expression might be regulated by steroid hormones. In support of this, we showed that in cultured endometrial tissues hCG and E2 alone had no effect on GLUT4 expression. However, P4 alone and P4 in combination with E2 decreased GLUT4 expression. Compared with non-PCOS controls, PCOS patients with endometrial hyperplasia exhibited decreased GLUT4 expression in particular in the epithelial cells. Conclusion We conclude that P4 can induce changes in endometrial GLUT4 expression during the menstrual cycle and that abnormal hormonal conditions such as PCOS disrupt normal patterns of GLUT4 expression in endometrial cells.

Dataset Information

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

Publications

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

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