The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments

Venkatesh, Varun; Grossmann, Mathis; Zajac, Jeffrey D; Davey, Rachel A

doi:10.1111/obr.13429

Cited by 14 publications

(12 citation statements)

References 353 publications

(467 reference statements)

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“…GO term and pathway enrichment analysis showed that DEGs were highly enriched in the present investigation, which undoubtedly verifies the reliability of our results. Signaling pathways include cytokine signaling in immune system [ [87], CES1 [88], CYP19A1 [89], PLAC8 [90], CD36 [91], GIPR (gastric inhibitory polypeptide receptor) [92], ARG1 [93], MSR1 [94], DOCK2 [95], S1PR1 [96], OXTR (oxytocin receptor) [97], F11R [98], LEPR (leptin receptor) [99], AR (androgen receptor) [100], DKK3 [101], FOXO1 [102], PIK3CB [103], WWP1 [104], PHIP (pleckstrin homology domain interacting protein) [105], MPZL3 [106], FBXO2 [107], GUCY2C [108], ADRA2A [109], CHRNA5 [110], GLP2R [111], SDC3 [112], NFAT5 [113], PON2 [114], PRNP (prion protein) [115], DGKE (diacylglycerol kinase epsilon) [116], ARHGAP21 [117], COQ2 [118], EPHX2 [119] and FAM3C [120] were observed to be associated with the progression of obesity. Vargas-Alarcón et al [121], Frantz et al [122], Bosè et al [123], Gu et al [124], Liu et al [125], Szirák et al [126], Ye et al [127], Alikhah et al [128], Chen et al [129], Mao et al…”

Section: Discussionmentioning

confidence: 99%

“…Signaling pathways include cytokine signaling in immune system [48], extracellular matrix organization [49], diseases of metabolism [50], hemostasis [51], innate immune system [52], metabolism of lipids [53] and metabolism [54] were linked with progression of PCOS. Altered expression of PLA2G5 [55], CASP1 [56], EDNRA (endothelin receptor type A) [57], F2RL1 [58], FOXP3 [59], DRD4 [60], COL6A3 [61], TIMP4 [62], SOCS1 [63], CD74 [64], TGFB1 [65], ATF5 [66], IRF7 [67], IRX3 [68], FOXC2 [69], STX1A [70], IL1RL1 [71], HHIP (hedgehog interacting protein) [72], ELOVL2 [73], BGN (biglycan) [74], POMC (proopiomelanocortin) [75], DOK5 [76], COL1A1 [77], POSTN (periostin) [78], SOD3 [79], ZNF423 [80], FABP5 [81], DDIT4 [82], KCTD15 [83], COL1A2 [84], MGAT2 [85], ENDOG (endonuclease G) [86], HSPA5 [87], CES1 [88], CYP19A1 [89], PLAC8 [90], CD36 [91], GIPR (gastric inhibitory polypeptide receptor) [92], ARG1 [93], MSR1 [94], DOCK2 [95], S1PR1 [96], OXTR (oxytocin receptor) [97], F11R [98], LEPR (leptin receptor) [99], AR (androgen receptor) [100], DKK3 [101], FOXO1 [102], PIK3CB [103], WWP1 [104], PHIP (pleckstrin homology domain interacting protein) [105], MPZL3 [106], FBXO2 [107], GUCY2C [108], ADRA2A [109], CHRNA5 [110], GLP2R [111], SDC3 [112], NFAT5 [113], PON2 [114], PRNP (prion protein) [115], DGKE (diacylglycerol kinase epsilon) [116], ARHGAP21 [117], COQ2 [118], EPHX2 [119] and FAM3C […”

Section: Discussionmentioning

confidence: 99%

“…To explore the moleculer pathogenesis of PCOS and its complications, we constructed PPI network and modules analysis for the reason that the DEGs would be grouped and ordered in the network judging by their interactions. HSPA5 [87] and AR (androgen receptor) [100] have been demonstrated to enhance obesity. Altered expression of HSPA5 [293], AR (androgen receptor) [309] and TCF4 [320] were associated with progression of cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we got hub genes, miRNA and TFs of PCOS and its complications. HSPA5 [87], F2RL1 [58], AR (androgen receptor) [100], SOCS1 [63], RUNX2 [542] and ESR1 [543] were an important participant in obesity. HSPA5 [293], AR (androgen receptor) [309], TCF4 [320], SOCS1 [255], PTN (pleiotrophin) [251], hsa-mir-21-3p [544], SOX2 [545], GATA2 [546], RUNX2 [547], DROSHA [548], ESR1 [549] and PAX3 [550] have been discovered to be involved in the cancer.…”

Section: Discussionmentioning

confidence: 99%

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The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Polycystic ovary syndrome (PCOS) is is associated with infertility, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, cardiovascular problems, neurological and psychological problems and cancer. The specific mechanism of PCOS and its complications remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of PCOS and its complications. The next generation squancing (NGS) datset GSE199225 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using HiPPIE and cytoscape. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed for research. The expression of the hub genes was validated using receiver operating characteristic (ROC) curve analysis. We have identified 957 DEGs in total, including 478 up regulated genes and 479 down regulated gene. GO and REACTOME illustrated that DEGs in PCOS were significantly enriched in regulation of molecular function, developmental process, interferon signaling and platelet activation, signaling and aggregation. Finally, through analyzing the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes HSPA5, PLK1, RIN3, DBN1, CCDC85B, DISC1, AR, MTUS2, LYN and TCF4 by the Cytoscape software. This study uses a series of bioinformatics technologies to obtain hug genes and key pathways related to PCOS and its complications. These analysis results provide us with novel ideas for finding biomarkers and treatment methods for PCOS and its complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

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“…The AR is known to affect the lipid cascade at multiple levels. 2 , 3 Till date, some studies have shown the role of AR in regulating the expression of cellular genes and proteins. Previously, in a study on multiple sclerosis, AR was observed to adversely regulate transcription factors of members of the Transforming growth factor TGFF-β/SMAD pathway.…”

Section: Introductionmentioning

confidence: 99%

Lipid Metabolic Disorders in Neurodegenerative Diseases – Role of Androgen Receptor

Sharma,

Saini,

Dhawan

2024

The Eurasian Journal of Medicine

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The challenge of managing neurodegenerative disorders is a worldwide concern, especially in the aging population. Neurodegenerative diseases are a varied group of disorders that are characterized by progressive degeneration of the structure and function of the nerve cells. Neurodegenerative diseases are increasing at an alarming rate, and hence there is an urgent need for an in-depth analysis of various metabolic malfunctions that alter the proper functioning of a cell. Lipid metabolism is a process that involves the synthesis and simultaneous degradation of lipids and encompasses a balance that is essential to maintain the structural and functional ability of a cell. Androgen receptor (AR) plays a critical role in regulating cellular functions. Recent studies have expanded our knowledge regarding direct or indirect interactions that occur among mitochondria, peroxisome, and androgen receptors, which play a crucial role in lipid homeostasis. Unusual levels of lipids and cholesterol due to receptor excitation or inhibition are associated with multiple diseases and have been a cause of concern. The androgen receptor, along with other receptors and proteins, forms an important metabolic cascade that, if altered, may cause the accumulation of lipids and result in neurodegenerative disorders. In this review, we underscore the role of the androgen receptor in regulating lipid and cholesterol levels during neurodegenerative disorders (Alzheimers, Parkinson’s, multiple sclerosis, and Huntington’s disease).

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How Food Choices Impact on Male Fertility

Pecora,

Sciarra,

Gangitano

et al. 2023

Curr Nutr Rep

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Purpose of Review Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting an association between nutrition and male fertility. Here, we have highlighted the impact of the various food groups on reproductive hormones and on spermatogenesis, and the effects of classical and latest dietary patterns such as Mediterranean diet, Western diet, intermittent fasting, ketogenic diet, and vegan/vegetarian diet on male fertility. Recent Findings Nutrients are the precursors of molecules involved in various body’s reactions; therefore, their balance is essential to ensure the correct regulation of different systems including the endocrine system. Hormones are strongly influenced by the nutritional status of the individual, and their alteration can lead to dysfunctions or diseases like infertility. In addition, nutrients affect sperm production and spermatogenesis, controlling sexual development, and maintaining secondary sexual characteristics and behaviors. Summary The consumption of fruit, vegetables, fish, processed meats, dairy products, sugars, alcohol, and caffeine importantly impact on male fertility. Among dietary patterns, the Mediterranean diet and the Western diet are most strongly associated with the quality of semen. Nutrients, dietary patterns, and hormonal levels have an impact on male infertility. Therefore, understanding how these factors interact with each other is important for strategies to improve male fertility.

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The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments

Cited by 14 publications

References 353 publications

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Lipid Metabolic Disorders in Neurodegenerative Diseases – Role of Androgen Receptor

How Food Choices Impact on Male Fertility

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