Brown Adipose Transplantation Improves Polycystic Ovary Syndrome-Involved Metabolome Remodeling

Yao, Lihua; Wang, Qin; Zhang, Runjie; Xingyun, Wang; Liu, Yiwen; Di, Fangfang; Song, Liwen; Xu, Siliang

doi:10.3389/fendo.2021.747944

Cited by 12 publications

(5 citation statements)

References 59 publications

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“…Blood phosphatidylcholine can be used as a chemical attractant to recruit immune cells such as macrophages and dendritic cells, thereby improving immune function [ 21 ]. These results were consistent with the conclusion of Yao et al [ 22 ], transplanting the brown adipose tissue in PCOS model mice. GPC/PC was significantly decreased in OB/OW PCOS patients, which was contrary to the conclusion of the previous study [ 18 ].…”

Section: Discussionsupporting

confidence: 93%

Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients

Gan,

Chen,

et al. 2023

International Journal of Endocrinology

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Background. Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age, whose clinical characteristics are hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovary, often accompanied by insulin resistance (IR) and metabolic abnormalities. Glucagon-like peptide (GLP)-1 receptor agonists (GLP-1Ra), such as exenatide, can bind to specific receptors on tissues such as the ovaries to improve the clinical phenotype of PCOS, while insulin-sensitizing agents, such as metformin, can also benefit to metabolic abnormalities in PCOS. Liquid chromatography-mass spectrometry (LC/MS) metabolomics revealed differences between the mechanisms of exenatide and metformin treatment of PCOS to some extent. Methods. In this study, 50 obese subjects with PCOS were randomly divided into the exenatide combined with metformin group (COM group, n = 28) and the metformin group (MF group, n = 22) for 12-week treatment. Before and after, serum samples were subjected to LC/MS analysis. Results. After treatment, there were 153 named differential metabolites in the COM group and 99 in the MF group. Most phosphatidylcholines (PC) and deoxycholic acid 3-glucuronide (DA3G) were significantly upregulated, while most glycerophosphoethanolamine (PE-NMe2), glycerophosphocholine (GPC), and threonine were downregulated in both groups. Only the decrease of neuromedin B, glutamate, and glutamyl groups and the increase of chenodeoxycholic acid sulfate docosadienoate (22: 2n6), and prostaglandin E2 have been observed in the COM group. In addition, salicylic acid and spisulosine increased and decanoylcarnitine decreased in the MF group. Both groups were enriched in glycerophospholipid, choline, and sphingolipid metabolism, while the COM group was especially superior in the glutamine and glutamate, bile secretion, and amino acid metabolism. Conclusion. Compared with metformin alone in the treatment of PCOS, the differential metabolites of the exenatide combined with metformin group are more extensive. The COM group may act on the hypothalamic-pituitary-gonadal axis (HPO) and its bypass, regulate multiple metabolism pathways such as phospholipids, amino acids, fatty acids, carnitine, bile acids, and glucose directly or indirectly in obese PCOS patients.

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Section: Discussionsupporting

confidence: 93%

Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients

Gan,

Chen,

et al. 2023

International Journal of Endocrinology

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“…The ability of hiGC to secret human‐derived natural steroid and convert testosterone to estradiol suggested that transplanting hiGC to PCOS individuals may alleviate PCOS syndrome. Although there is study that suggested cell transplantation as a therapeutic strategy for PCOS, 35 we did not find pre‐existing studies that directly use granulosa cells as transplants for PCOS treatment. Therefore, we established a DHEA‐induced PCOS mouse model as previously described 18 and tested the effect of hiGC transplantation on the polycystic ovaries (Figure 7A).…”

Section: Resultsmentioning

confidence: 99%

FOXL2 and NR5A1 induce human fibroblasts into steroidogenic ovarian granulosa‐like cells

Wen,

Ding,

Wang

et al. 2024

Cell Proliferation

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Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To address this problem, it is necessary to induce functional granulosa cells at different stages in vitro. In this study, we established a reprogramming method to induce early‐ and late‐stage granulosa cells with different steroidogenic abilities. We used an AMH‐fluorescence‐reporter system to screen candidate factors for cellular reprogramming and generated human induced granulosa‐like cells (hiGC) by overexpressing FOXL2 and NR5A1. AMH‐EGFP+ hiGC resembled human cumulus cells in transcriptome profiling and secreted high levels of oestrogen and progesterone, similar to late‐stage granulosa cells at antral or preovulatory stage. Moreover, we identified CD55 as a cell surface marker that can be used to isolate early‐stage granulosa cells. CD55+ AMH‐EGFP‐ hiGC secreted high levels of oestrogen but low levels of progesterone, and their transcriptome profiles were more similar to early‐stage granulosa cells. More importantly, CD55+ hiGC transplantation alleviated polycystic ovary syndrome (PCOS) in a mouse model. Therefore, hiGC provides a cellular model to study the developmental program of human granulosa cells and has potential to treat PCOS.

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“…Polycystic ovary syndrome (PCOS) is a serious clinical condition that is related to metabolic and reproductive dysfunction and is characterized by abnormal menstrual cycles, anovulation, insulin resistance (IR), and hyperandrogenemia (HA) [ 1 ]. HA is the primary cause of anovulatory infertility and affects approximately 5–20% of women of childbearing age [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide-1 receptor agonists decrease hyperinsulinemia and hyperandrogenemia in dehydroepiandrosterone-induced polycystic ovary syndrome mice and are associated with mitigating inflammation and inducing browning of white adipose tissue

Zhang

Lin

et al. 2023

Biology of Reproduction

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Polycystic ovary syndrome (PCOS) is a complicated hormonal and metabolic disorder with hyperandrogenemia, insulin resistance and reproductive dysfunction. The exact pathogenesis of PCOS with high clinical heterology and high morbidity is not clear thus far. Inflammation is involved in the progression of PCOS. In addition, brown adipose tissue (BAT) activity is impaired in PCOS. Interestingly, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been reported to alleviate inflammation and promote browning of white adipose tissue. In this study, the effects of GLP-1RAs on PCOS mice were explored. Twenty-four mice were randomly assigned into four groups: Control, dehydroepiandrosterone (DHEA), DHEA+Liraglutide and DHEA+Semaglutide. The glucose tolerance, insulin tolerance, estrous cycle, sex hormone levels and serum inflammatory cytokine levels were measured after GLP-1RAs intervention for four weeks. qPCR and western blotting were utilized to evaluate the expression of steroidogenic enzymes and BAT marker. Glucose metabolism in PCOS mice was ameliorated by GLP-1RAs, while the reproductive endocrine disorder of PCOS mice was partially reversed. The mRNA levels of steroidogenic enzymes and the expression of inflammatory mediators in serum and ovaries of PCOS mice were improved. Furthermore, toll-like receptor 4 and phosphorylation of nuclear factor-kappa B protein levels were decreased by GLP-1RAs in ovary. Notably, after GLP-1RAs intervention, the expression of BAT marker levels was considerably raised in the white adipose tissue of PCOS mice. In conclusion, the hyperinsulinemia and hyperandrogenemia of PCOS mice were alleviated by GLP-1RAs intervention, which was associated with mitigating inflammation and stimulating adipose tissue browning.

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Brown Adipose Transplantation Improves Polycystic Ovary Syndrome-Involved Metabolome Remodeling

Cited by 12 publications

References 59 publications

Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients

Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients

FOXL2 and NR5A1 induce human fibroblasts into steroidogenic ovarian granulosa‐like cells

Glucagon-like peptide-1 receptor agonists decrease hyperinsulinemia and hyperandrogenemia in dehydroepiandrosterone-induced polycystic ovary syndrome mice and are associated with mitigating inflammation and inducing browning of white adipose tissue

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