White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice

Silva, Lorena Doretto da; Steiner, Marcelo Luis; Veridiano, Juliana Mora; Petri, Giuliana; Luz, Maria Cláudia de Brito; Neofiti-Papi, Bianca; Bianco, Bianca; Fonseca, Fernando Luiz Affonso; Toledo, O. M. S.; Fernandes, César Eduardo; Pompei, Luciano de Melo

doi:10.1080/09513590.2020.1772228

Cited by 4 publications

(4 citation statements)

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“…is the only one to investigate the relationships between androgens and BMAT in women, and none of the androgens, including FT, TT, and SHBG, showed a significant association with BMAT in older postmenopausal women ( 48 ). In the female rodent models of PCOS induced by testosterone propionate or dehydroepiandrosterone (DHEA), lower marrow fat volume was detected in the normal control group and the group with a shorter injection period, which demonstrated that the increase in BMAT was due to exogenous testosterone ( 14 , 15 ). In overweight and obese PCOS patients, FT and SHBG were also not associated with increased BMAT, even though their levels increased in varying degrees, but TT was shown to be a risk factor for elevated BMAT despite the lack of a linear association with BMAT.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is not known whether PCOS-related obesity and metabolic abnormalities in women lead to an increase in BMAT. The adverse effect of hyperandrogenism on increased BMAT, confirmed in rodent models, has not been verified in women with PCOS ( 14 , 15 ). In this study, we aimed to explore the phenotype of BMAT in overweight or obese young PCOS patients and furthermore to investigate the relationships between the increase in BMAT and hyperandrogenism, obesity, and metabolic disorders in PCOS.…”

Section: Introductionmentioning

confidence: 94%

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Marrow adipose tissue is increased in overweight and obese women with PCOS independently of hyperandrogenism related obesity and metabolic disorders

Min

et al. 2023

Front. Endocrinol.

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PurposeThis study aimed to investigate the increase in bone marrow adipose tissue (BMAT) in overweight and obese women with polycystic ovary syndrome (PCOS) and its relationship with hyperandrogenism, obesity, and metabolic disorders.MethodsThe study included 87 overweight or obese women with PCOS (mean age 29 ± 4 years), as well as 87 age-matched controls recruited from a separate population study. All PCOS patients were measured for anthropometric features, abdominal adipose tissue areas, BMAT, biochemistry, and sex hormones. BMAT was compared between the PCOS patients and controls. In PCOS patients, subgroup comparisons of BMAT and its associations with body adiposity indices, biochemistry, and sex hormones were analyzed. The odds ratios (ORs) of elevated BMAT (defined as BMAT ≥ 38%) were calculated.ResultsOn average BMAT was increased by 5.6% ( ± 11.3%) in PCOS patients compared to controls. BMAT were significantly higher in the upper tertiles of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). BMAT was not correlated with abdominal adiposity indices or biochemistry except for LDL-C (r = 0.253—0.263, p = 0.014—0.018). LDL-C was not significantly different between the normal and abnormal androgen PCOS subgroups (p = 0.10-0.887). LDL-C, follicle stimulating hormone (FSH), and total testosterone (TT) were risk factors for elevated BMAT, with ORs of 1.899 (p = 0.038-0.040), 1.369 (p = 0.030-0.042), and 1.002 (p = 0.040-0.044) for each unit increase, respectively.ConclusionBMAT was increased in overweight and obese PCOS patients, but the increase in BMAT was not associated with the hyperandrogenism related obesity or metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Marrow adipose tissue is increased in overweight and obese women with PCOS independently of hyperandrogenism related obesity and metabolic disorders

Min

et al. 2023

Front. Endocrinol.

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“…5,6 Recent research in rat models of PCOS has shown that BAT activity is significantly reduced compared to normal rats and that BAT transplantation alleviates the metabolic and reproductive defects of PCOS animals, while dihydroepiandrosterone (DHEA) contributes to increased insulin resistance, and influences the expression of adipokines in DHEA-induced PCOS mice. 7,8 Bile acids (BAs) are produced from cholesterol, 9 and the composition of the BA pool is altered by the gut microbiota, which transform primary BAs into secondary BAs through dehydrogenation and dihydroxylation. 10 BAs stimulate Takeda G-protein-coupled receptor 5 (TGR5), which increases BAT and WAT browning by activating the UCP1 signaling pathway to regulate thermogenesis and energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electroacupuncture improves metabolic and ovarian function in a rat model of polycystic ovary syndrome by decreasing white adipose tissue, increasing brown adipose tissue, and modulating the gut microbiota

Zhang

Tong

et al. 2021

Acupunct Med

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Background: Polycystic ovary syndrome (PCOS) affects 8%–15% of reproductive-age women and is associated with reproductive disorders, abdominal obesity, hyperinsulinemia, insulin resistance, type 2 diabetes, and cardiovascular diseases. Acupuncture, as a traditional physical therapy method, could affect various metabolic disorders such as obesity, hyperplasia, gout, and cardiovascular and cerebrovascular diseases in clinical practice. Moreover, electroacupuncture (EA) has been shown to decrease body weight in rats with PCOS; however, the mechanism of weight loss and the relationship between adipose tissue and gut microbiota remain unclear. Objective: To explore the effect and mechanism of EA on white and brown adipose tissues and gut microbiota, and its follow-up effect on reproductive function, in a rat model of PCOS. Methods: Daily EA treatment was administered at ST29 and SP6 in a dihydrotestosterone (DHT)-induced PCOS-like rat model (PCOS + EA group). Effects of EA on in vivo and in vitro adipose volume and weight, organ weight coefficients, body weight, hormonal profiles, and estrous cyclicity were measured, and compared with untreated PCOS model rats (PCOS group) and healthy rats (control group). Microbial DNA was extracted from the fecal samples to analyze group abundance and diversity. Results: EA improved estrous cyclicity, decreased body weight, decreased visceral and subcutaneous fat content, and increased brown adipose tissue weight. EA also normalized serum DHT and progesterone levels and improved glucose tolerance. There were few significant differences in the composition or diversity of the gut microbiota between control, PCOS, and PCOS + EA groups, except for the relative abundances of Tenericutes at the phylum level and Prevotella_9 at the genus level, which were significantly different in the PCOS group before and after EA treatment. Both are important microflora, strongly related to body weight. Conclusion: EA regulated the metabolic disorders and improved reproductive function in this PCOS-like rat model by adjusting visceral fat and brown fat, as well as intestinal flora.

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Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS

Hong,

Xiao,

Diao

et al. 2024

Cell. Mol. Life Sci.

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Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.

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White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice

Cited by 4 publications

References 31 publications

Marrow adipose tissue is increased in overweight and obese women with PCOS independently of hyperandrogenism related obesity and metabolic disorders

Marrow adipose tissue is increased in overweight and obese women with PCOS independently of hyperandrogenism related obesity and metabolic disorders

Electroacupuncture improves metabolic and ovarian function in a rat model of polycystic ovary syndrome by decreasing white adipose tissue, increasing brown adipose tissue, and modulating the gut microbiota

Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS

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