Nonhormonal therapy for endometriosis based on energy metabolism regulation

Kobayashi, Hiroshi; Shinmoto, Hiroshi; Imanaka, Shogo

doi:10.1530/raf-21-0053

Cited by 22 publications

(32 citation statements)

References 90 publications

(242 reference statements)

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“…Endometriotic cells convert significant amounts of glucose into energy to undergo growth in hypoxic milieus. 7 Recent studies suggest that reprogramming of energy metabolism is a hallmark of endometriosis development. 6 , 11 , 12 , 13 First, we focus on how endometriotic cells dynamically reconstruct signaling pathways that regulate glucose metabolism in the maintenance of energy homeostasis and summarize the underlying key regulators.…”

Section: Resultsmentioning

confidence: 99%

“…Changing environmental conditions are reported to accelerate a cellular metabolic switch from glycolysis to mitochondrial oxidative phosphorylation or vice versa. 7 …”

Section: Resultsmentioning

confidence: 99%

“…In addition, like cancer, endometriosis requires the fuel to adapt and grow in hypoxic and harsh environments. 6 , 7 Several molecular similarities between cancer and endometriosis have been reported in terms of the reprogramming of energy metabolism. 8 , 9 , 10 Human cell utilizes glucose as a primary source of energy, and adenosine triphosphate (ATP) is generated from glucose via glycolysis and mitochondrial oxidative phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

“… 6 , 11 , 12 , 13 A review article focusing on the unique aspect of metabolic reprogramming of endometriosis has been reported. 7 The cellular metabolic shift from oxidative phosphorylation to glycolysis suppresses endometriotic cell death through decreasing the level of mitochondrial reactive oxygen species (ROS) generation. Changing the specific metabolic switch toward oxidative phosphorylation leads to cell death by causing increased ROS production and severe oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review

Kobayashi

Imanaka

2022

Reprod Medicine & Biology

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Background Endometriosis is an estrogen‐dependent disease and causes pelvic pain and infertility. The limits of current pharmacotherapy in women who desire to become pregnant prompt the development of various targeted molecules for more effective treatment. A review article focused on the unique aspect of cellular metabolic reprogramming of endometriotic cells has been reported. The cellular metabolic pathways are reprogrammed to adapt to a variety of environmental stresses (e.g., nutrient starvation or glucose deprivation, hypoxic stress, excessive reactive oxygen species generation, and other environmental factors). This review aims to summarize macrophage polarization and metabolic reprogramming in endometriosis. Methods A literature search was performed between January 2000 and March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. Results Macrophage cellular metabolism has a marked influence on its phenotype and function. Preclinical studies showed that metabolic conversion toward glycolysis or oxidative phosphorylation drives macrophage polarization to M1 or M2 phenotype, respectively. Such cellular metabolic rewiring can offer new therapeutic opportunities. Conclusion A better understanding of metabolic reprogramming biology in endometriosis‐associated macrophages is essential in considering novel therapeutic approach for endometriosis. However, there are currently no detailed studies on therapeutic strategies targeting the cellular metabolic properties of endometriosis‐associated macrophages.

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Section: Resultsmentioning

confidence: 99%

“…Changing environmental conditions are reported to accelerate a cellular metabolic switch from glycolysis to mitochondrial oxidative phosphorylation or vice versa. 7 …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review

Kobayashi

Imanaka

2022

Reprod Medicine & Biology

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“…A review by Viganò et al (2012) showed that BMI is reduced in women with endometriosis [ 5 ]. A possibility of non-hormonal therapy of endometriosis based on the regulation of energy metabolism is being studied [ 6 , 7 ]. However, the factors of energy metabolism in PF and their role in the development of endometriosis remain underestimated.…”

Section: Introductionmentioning

confidence: 99%

The Levels of Ghrelin, Glucagon, Visfatin and Glp-1 Are Decreased in the Peritoneal Fluid of Women with Endometriosis along with the Increased Expression of the CD10 Protease by the Macrophages

Krasnyi

Sadekova

Smolnova

et al. 2022

IJMS

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The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (p = 0.007, p = 0.009, p = 0.002, p = 0.008, respectively). At the same time, there was a noted increase in the CD10 protease expression by peritoneal macrophages (p = 0.044). Correlation analysis showed a positive correlation of ghrelin and GLP-1 levels with CD86 macrophage expression (p = 0.044, p = 0.022, respectively) in the study group; a positive correlation was also found between the levels of GLP-1, glucagon, and visfatin with CD26 macrophage expression (p = 0.041, p = 0.048, p = 0.015, respectively) in PF. No correlations were found in the control group. These results indicate that a decrease in the levels of ghrelin, GLP-1, glucagon, and visfatin in PF may contribute to endometriosis development through their impact on the expression of pro-inflammatory markers of PF macrophages.

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Establishment of a novel glycolysis-immune-related diagnosis gene signature for endometriosis by machine learning

Chen

Jiao

Yin

et al. 2023

J Assist Reprod Genet

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Purpose The objective of this study was to investigate the key glycolysis-related genes linked to immune cell infiltration in endometriosis and to develop a new endometriosis (EMS) predictive model. Methods A training set and a test set were created from the Gene Expression Omnibus (GEO) public database. We identified five glycolysis-related genes using least absolute shrinkage and selection operator (LASSO) regression and the random forest method. Then, we developed and tested a prediction model for EMS diagnosis. The CIBERSORT method was used to compare the infiltration of 22 different immune cells. We examined the relationship between key glycolysis-related genes and immune factors in the eutopic endometrium of women with endometriosis. In addition, Gene Ontology (GO)-based semantic similarity and logistic regression model analyses were used to investigate core genes. Reverse real-time quantitative PCR (RT-qPCR) of 5 target genes was analysed. Results The five glycolysis-related hub genes (CHPF, CITED2, GPC3, PDK3, ADH6) were used to establish a predictive model for EMS. In the training and test sets, the area under the curve (AUC) of the receiver operating characteristic curve (ROC) prediction model was 0.777, 0.824, and 0.774. Additionally, there was a remarkable difference in the immune environment between the EMS and control groups. Eventually, the five target genes were verified by RT-qPCR. Conclusion The glycolysis-immune-based predictive model was established to forecast EMS patients’ diagnosis, and a detailed comprehension of the interactions between endometriosis, glycolysis, and the immune system may be vital for the recognition of potential novel therapeutic approaches and targets for EMS patients.

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Nonhormonal therapy for endometriosis based on energy metabolism regulation

Cited by 22 publications

References 90 publications

Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review

Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review

The Levels of Ghrelin, Glucagon, Visfatin and Glp-1 Are Decreased in the Peritoneal Fluid of Women with Endometriosis along with the Increased Expression of the CD10 Protease by the Macrophages

Establishment of a novel glycolysis-immune-related diagnosis gene signature for endometriosis by machine learning

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