scholarly journals Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before and after Exercise

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Changzhuan Shao ◽  
Yiming Ren ◽  
Zinan Wang ◽  
Chenzhe Kang ◽  
Hongke Jiang ◽  
...  

Purpose. The aim of the present study was to elucidate the metabolic mechanisms associated with chronic fatigue syndrome (CFS) via an analysis of urine metabolites prior to and following exercise in a rat model. Methods. A rat model of CFS was established using restraint-stress, forced exercise, and crowded and noisy environments over a period of 4 weeks. Behavioral experiments were conducted in order to evaluate the model. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS) in combination with multivariate statistical analysis before and after exercise. Results. A total of 20 metabolites were detected in CFS rats before and after exercise. Three metabolic pathways (TCA cycle; alanine, aspartate, and glutamate metabolism; steroid hormone biosynthesis) were significantly impacted before and after exercise, while sphingolipid metabolism alone exhibited significant alterations after exercise only. Conclusion. In addition to metabolic disturbances involving some energy substances, alterations in steroid hormone biosynthesis and sphingolipid metabolism were detected in CFS rats. Sphingosine and 21-hydroxypregnenolone may be key biomarkers of CFS, potentially offering evidence in support of immune dysfunction and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity in patients with CFS.

Polymers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1269 ◽  
Author(s):  
Changzhuan Shao ◽  
Jing Song ◽  
Shanguang Zhao ◽  
Hongke Jiang ◽  
Baoping Wang ◽  
...  

Ziyang green tea was considered a medicine food homology plant to improve chronic fatigue Ssyndrome (CFS) in China. The aim of this research was to study the therapeutic effect of selenium-polysaccharides (Se-TP) from Ziyang green tea on CFS and explore its metabolic mechanism. A CFS-rats model was established in the present research and Se-TP was administrated to evaluate the therapeutic effect on CFS. Some serum metabolites including blood urea nitrogen (BUN), blood lactate acid (BLA), corticosterone (CORT), and aldosterone (ALD) were checked. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS). Multivariate statistical analysis was also used to check the data. The results selected biomarkers that were entered into the MetPA database to analyze their corresponding metabolic pathways. The results demonstrated that Se-TP markedly improved the level of BUN and CORT in CFS rats. A total of eight differential metabolites were detected in GC-MS analysis, which were benzoic acid, itaconic acid, glutaric acid, 4-acetamidobutyric acid, creatine, 2-hydroxy-3-isopropylbutanedioic acid, l-dopa, and 21-hydroxypregnenolone. These differential metabolites were entered into the MetPA database to search for the corresponding metabolic pathways and three related metabolic pathways were screened out. The first pathway was steroid hormone biosynthesis. The second was tyrosine metabolism, and the third was arginine-proline metabolism. The 21-hydroxypregnenolone level of rats in the CFS group markedly increased after the Se-TP administration. In conclusion, Se-TP treatments on CFS rats improved their condition. Its metabolic mechanism was closely related to that which regulates the steroid hormone biosynthesis.


2008 ◽  
Vol 31 (6) ◽  
pp. 319 ◽  
Author(s):  
Anita A Thambirajah ◽  
Kenna Sleigh ◽  
H. Grant Stiver ◽  
Anthony W Chow

Purpose: Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness. Methods: HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise. Results: Basal HSP27 was higher among CFS patients than in controls (0.54 ± 0.13 vs. 0.19 ± 0.06, mean ± SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 ± 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 ± 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 ± 0.40 vs. 1.32 ± 0.46; P < 0.05), and for HSP90 (0.34 ± 0.09 vs. 0.49 ± 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 ± 0.27) and day 7 (1.24 ± 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 ± 0.06) (P < 0.05, respectively). Conclusion: These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.


2021 ◽  
Vol 5 (1) ◽  
pp. 027-030
Author(s):  
Shah Rajit J

Chronic fatigue syndrome (CFS) is a poorly-understood respiratory condition that affects millions of individuals. Hyperbaric oxygen therapy (HBOT) is a treatment option being considered to address CFS as it is suggested to combat fatigue and increase oxygenation. HBOT provides two opportunities in advancing research of CFS: it may provide data on symptom amelioration and be utilized in the search for a biomarker. By either identifying biomarkers before using HBOT to compare epigenomes of patients before and after treatment or using HBOT to find epigenetic discrepancies between patients with and without treatment, matching epigenetic regulation with symptom amelioration may significantly advance the understanding of the etiology and treatment mechanism for CFS. EPAS1/HIF-2α is a leading candidate for an epigenetic biomarker as it responds differentially to hypoxic and normoxic conditions, which degrades more slowly in hypoxic conditions. Epigenetic regulation of EPAS1/HIF-2α in such differential conditions may be explored in HBOT experiments. In addition to HBOT as a promising treatment option for CFS symptoms, it may aid the identification of biomarkers in CFS. Further research into both outcomes is strongly encouraged.


2022 ◽  
Vol 12 (1) ◽  
pp. 78
Author(s):  
James N. Baraniuk ◽  
Alison Amar ◽  
Haris Pepermitwala ◽  
Stuart D. Washington

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and control subjects underwent fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction. Methods: Activated midbrain nuclei were inferred by a re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI subjects showed greater activation during cognition than ME/CFS in the left pedunculotegmental nucleus. Post exercise, ME/CFS subjects showed greater activation than GWI ones for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI, indicating reciprocal patterns of activation. The controls had no changes. Conclusions: Exercise caused the opposite effects with increased activation in ME/CFS but decreased activation in GWI, indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 905-905
Author(s):  
Abigail Corkum ◽  
Qu Tian ◽  
Luigi Ferrucci

Abstract Red blood cell distribution width (RDW) describes the amount of variation in blood cell volume and size and increases with age. Higher RDW predicts all-cause mortality, metabolic syndrome, diabetes, and markers of glycemic control, such as glycosylated hemoglobin. However, mechanisms that connect high RDW with these health outcomes are unknown. Thus, identification of high risk in these patients cannot be addressed. This study aims to identify metabolites and pathways that are associated with high levels of RDW in community-dwelling older adults. Using data from the Baltimore Longitudinal Study of Aging, we identified 1,004 cognitively normal participants (mean age: 67.1±13, 48% women, 26% black) with concurrent data on RDW and comprehensive targeted plasma metabolites by Biocrates p500. Participants were grouped into RDW quartiles (Q1:14%). Associations of metabolites with quartiles of RDW were examined using multivariable linear regression with Q1 being the reference group. Models were adjusted for age, sex, and race. Compared to Q1, Q4 had higher concentrations of SM(OH)C14:1, PC ae C30:2, and hypoxanthine, and lower concentrations of DHEAS, Cortisol, Tryptophan, and Hex2Cer(d/18:1/24:0) (all p&lt;0.01). These metabolites are critical components of sphingolipid metabolism and steroid hormone biosynthesis pathways. Elevated RDW was associated with metabolites derived from classes of hormones, amino acids, ceramides, sphingomyelins, PCs, and nucleobases. Individuals with elevated RDW (i.e. ≥14%) may have disrupted sphingolipid metabolism and steroid hormone biosynthesis. These pathways can be targeted for prevention.


2021 ◽  
Vol 10 (13) ◽  
pp. 2795
Author(s):  
Sławomir Kujawski ◽  
Anna M. Bach ◽  
Joanna Słomko ◽  
Derek F. H. Pheby ◽  
Modra Murovska ◽  
...  

This study represents a comparison of the functional interrelation of fatigue and cognitive, cardiovascular and autonomic nervous systems in a group of Chronic Fatigue Syndrome (CFS) patients compared with those in healthy individuals at different stages of analysis: at baseline and after changes induced by whole-body cryotherapy (WBC) combined with a static-stretching (SS) program. The study included 32 patients (Fukuda criteria) and 18 healthy controls. Fatigue, cognitive, cardiovascular and autonomic function and arterial stiffness were measured before and after 10 sessions of WBC with SS. In the patients, a disturbance in homeostasis was observed. The network relationship based on differences before and after intervention showed comparatively higher stress and eccentricity in the CFS group: 50.9 ± 56.1 vs. 6.35 ± 8.72, p = 0.002, r = 0.28; and 4.8 ± 0.7 vs. 2.4 ± 1, p < 0.001, r = 0.46, respectively. Before and after intervention, in the CFS group increased fatigue was related to baroreceptor function, and baroreceptor function was in turn related to aortic stiffness, but no such relationships were observed in the control group. Differences in the network structure underlying the interrelation among the four measured criteria were observed in both groups, before the intervention and after ten sessions of whole cryotherapy with a static stretching exercise.


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