Metabolomics analysis reveals metabolic changes associated with trans-resveratrol treatment in experimental cryptorchidism mice

2021 ◽  
Vol 33 (5) ◽  
pp. 328
Author(s):  
Siqiang Li ◽  
Yun Li ◽  
Fujia Chen ◽  
Yurong Yang ◽  
Li Song ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Immunoblot Analysis ◽  
Untargeted Metabolomics ◽  
Uridine Diphosphate ◽  
Biosynthesis Pathway ◽  
Biochemical Pathways ◽  
Chromatography Tandem Mass Spectrometry ◽  
Hexosamine Biosynthesis ◽  
Liquid Chromatography Tandem Mass ◽  
Hexosamine Biosynthesis Pathway

This study aimed to analyse global metabolomic changes associated with trans-resveratrol (RSV) treatment in mice with cryptorchidism using untargeted metabolomics. Cryptorchidism was established surgically in Kunming mice, which were then treated with 20µg g–1 day–1, s.c., RSV for 35 consecutive days. Typical manifestations of spermatogenesis arrest were seen in mice with cryptorchidism, and RSV treatment for 35 days restored spermatogenesis. Liquid chromatography–tandem mass spectrometry was used to profile the metabolome of testes from mice in the control (non-cryptorchid, untreated), cryptorchid and RSV-treated cryptorchid groups. In all, 1386 and 179 differential metabolites were detected in the positive and negative modes respectively. Seven and six potential biomarkers were screened for spermatogenesis arrest and restoration respectively. Pathway analysis showed changes in 197 metabolic pathways. The hexosamine biosynthesis pathway was inhibited in the cryptorchid group, which probably resulted in a decrease in the end product, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Immunoblot analysis showed that total testicular protein O-linked β-N-acetylglucosamine glycosylation was related to spermatogenesis arrest, further indicating a decrease in UDP-GlcNAc in the cryptorchid group. Thus, untargeted metabolomics revealed the biochemical pathways associated with the restoration of metabolic status in the cryptorchid group following RSV treatment and the findings could be used to monitor the response to RSV treatment. This study provides a meaningful foundation for the future clinical application of RSV in the treatment of spermatogenesis dysfunction.

scholarly journals Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Angela Tolwani ◽  
Magdalena Matusiak ◽  
Nam Bui ◽  
Erna Forgó ◽  
Sushama Varma ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Reprogramming ◽  
Biosynthesis Pathway ◽  
Metastatic Tumors ◽  
Pathway Activation ◽  
Hexosamine Biosynthesis ◽  
Rate Limiting ◽  
Hexosamine Biosynthesis Pathway ◽  
Independent Cohort ◽  
High Metabolic Activity

AbstractMetabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.

Hexosamine biosynthesis pathway flux promotes endoplasmic reticulum stress, lipid accumulation, and inflammatory gene expression in hepatic cells

2010 ◽  
Vol 298 (3) ◽  
pp. E499-E511 ◽  
Author(s):  
Andrew T Sage ◽  
Lisa A Walter ◽  
Yuanyuan Shi ◽  
Mohammad I. Khan ◽  
Hideaki Kaneto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Expression System ◽  
Immunoblot Analysis ◽  
Biosynthesis Pathway ◽  
Hepatic Cells ◽  
Hexosamine Biosynthesis ◽  
Hexosamine Biosynthesis Pathway

There is increasing evidence that endoplasmic reticulum (ER) stress contributes to the development of atherosclerosis in diabetes mellitus. The purpose of this study was to determine the effects of increased hexosamine biosynthesis pathway (HBP) flux on ER stress levels and the complications of ER stress associated with diabetes and atherosclerosis in hepatic cells. Glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme of the HBP, was overexpressed in HepG2 cells by use of an adenoviral expression system. The ER stress response and downstream effects, including activation of lipid and inflammatory pathways, were determined using real-time PCR, immunoblot analysis, and cell staining techniques. GFAT overexpression resulted in increased expression of ER stress markers, including Grp78, Grp94, calreticulin, and GADD153, relative to cells infected with an empty adenoviral vector. In addition, GFAT overexpression promoted lipid, but not cholesterol, accumulation in hepatic cells as well as inflammatory pathway activation. Treatment with 6-diazo-5-oxo-norleucine, a GFAT antagonist, blocked the effects of GFAT overexpression. Consistent with our in vitro data, hyperglycemic mice presented with elevated markers of hepatic ER stress, glucosamine and lipid accumulation. Together, these data suggest that HBP flux-induced ER stress plays a role in the development of hepatic steatosis and atherosclerosis under conditions of hyperglycemia.

266-LB: Evidence for a Hexosamine Biosynthesis Pathway-Mediated Sp1 Cholesterolgenic Response Being an Early Etiological Factor of Insulin Resistance

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 266-LB
Author(s):  
BRIAN A. GRICE ◽  
JACOB D. COVERT ◽  
ALEC M. KREILACH ◽  
MATTHEW THORNBURG ◽  
LIXUAN TACKETT ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Etiological Factor ◽  
Biosynthesis Pathway ◽  
Hexosamine Biosynthesis ◽  
Hexosamine Biosynthesis Pathway

scholarly journals Acute Regulation of Cardiac Metabolism by the Hexosamine Biosynthesis Pathway and Protein O-GlcNAcylation

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18417 ◽  
Author(s):  
Boglárka Laczy ◽  
Norbert Fülöp ◽  
Arzu Onay-Besikci ◽  
Christine Des Rosiers ◽  
John C. Chatham
Keyword(s):  
Cardiac Metabolism ◽  
Biosynthesis Pathway ◽  
Hexosamine Biosynthesis ◽  
Hexosamine Biosynthesis Pathway

scholarly journals Impact of type‐2 diabetes on the hexosamine biosynthesis pathway and protein O‐glycosylation

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Norbert Fülöp ◽  
Peipei Wang ◽  
Richard B Marchase ◽  
John C Chatham
Keyword(s):  
Type 2 Diabetes ◽  
Biosynthesis Pathway ◽  
Hexosamine Biosynthesis ◽  
Hexosamine Biosynthesis Pathway

scholarly journals The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer

2020 ◽  
Vol 2 (12) ◽  
pp. 1401-1412
Author(s):  
Jiyeon Kim ◽  
Hyun Min Lee ◽  
Feng Cai ◽  
Bookyung Ko ◽  
Chendong Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Biosynthesis Pathway ◽  
Hexosamine Biosynthesis ◽  
Hexosamine Biosynthesis Pathway
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