scholarly journals Comprehensive Evaluation of Caloric Restriction-Induced Changes In The Metabolome Profile of Mice

Author(s):  
Dadi Xie ◽  
Jinxi Huang ◽  
Qiang Zhang ◽  
Shiyuan Zhao ◽  
Hongjia Xue ◽  
...  

Abstract Objects: Caloric restriction (CR) is known to extend lifespan and exert a protective effect on organs, and is thus a low-cost and easily implemented approach to the health maintenance. However, there have been no studies that have systematically evaluated the metabolic changes that occur in the main tissues affected by CR. This study aimed to explore the target tissues metabolomic profile in CR mice.Methods: Male C57BL/6J mice were randomly allocated to the CR group (n = 7) and control group (n = 7). A non-targeted gas chromatography–mass spectrometry (GC–MS) approach and multivariate analysis were used to identify metabolites in the main tissues (serum, heart, liver, kidney, cortex, hippocampus, lung, muscle, and white adipose) in model of CR. Results: We identified 10 metabolites in the heart that showed differential abundance between the 2 groups, along with 9 in kidney, 7 in liver, 6 in lung, 6 in white adipose, 4 in hippocampus, 4 in serum, 3 in cortex, and 2 in muscle. The most significantly altered metabolites were amino acids (AAs) (glycine, aspartic acid, l-isoleucine, l-proline, l-aspartic acid, l-serine, l-hydroxyproline, l-alanine, l-valine, l-threonine, l-glutamic acid, and phenylalanine) and fatty acids (FAs) (palmitic acid, 1-monopalmitin, glycerol monostearate, docosahexaenoic acid, 16-octadecenoic acid, oleic acid, stearic acid, and hexanoic acid). These metabolites were associated with 8 different functional pathways related to the metabolism of AAs, lipids, and energy. Conclusion: Our results provide insight into the specific metabolic changes that are induced by CR and can serve as a reference for physiologic studies on how CR improves health and extends lifespan.

2017 ◽  
Vol 36 (12) ◽  
pp. 1286-1294 ◽  
Author(s):  
J Yu ◽  
H Wu ◽  
Z Lin ◽  
K Su ◽  
J Zhang ◽  
...  

Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg−1 SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography–mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2745
Author(s):  
Peng Du ◽  
Jia Song ◽  
Huirui Qiu ◽  
Haorui Liu ◽  
Li Zhang ◽  
...  

Shanxi-aged vinegar, a traditional Chinese grain-fermented food that is rich in polyphenols, has been shown to have therapeutic effects on a variety of diseases. However, there has been no comprehensive evaluation of the anti-inflammatory activity of polyphenols extracted from Shanxi-aged vinegar (SAVEP) to date. The anti-inflammatory activities of SAVEP, both in RAW 264.7 macrophages and mice, were extensively investigated for the potential application of SAVEP as a novel anti-inflammatory agent. In order to confirm the notion that polyphenols could improve inflammatory symptoms, SAVEP was firstly detected by gas chromatography mass spectrometry (GC-MS). In total, 19 polyphenols were detected, including 12 phenolic acids. The study further investigated the protective effect of SAVEP on lipopolysaccharide-induced inflammation in RAW264.7 macrophages and ICR mice. The results showed that compared with those of the model group, SAVEP could remarkably recover the inflammation of macrophage RAW264.7 and ICR mice. SAVEP can normalise the expression of related proteins via the suppression of MAPK/NF-κB pathway activation, inhibiting the expression of iNOS and COX-2 proteins, and consequently the production of inflammatory factors, thus alleviating inflammatory stress. These results suggest that SAVEP may have a potential function against inflammation.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fried ◽  
V.Y Reddy ◽  
P Neuzil ◽  
R Rosen ◽  
P Sramkova ◽  
...  

Abstract Background/Introduction Obesity and its comorbid conditions (i.e. type II diabetes mellitus, atrial fibrillation, coronary artery disease, hypertension, etc...) is a growing burden globally, however, the current treatments (i.e. bariatric surgery, intragasrtic balloons and/or pharmaceutical therapy) pose substantial risks or are contraindicated for various populations. Transcatheter bariatric embolotherapy of left gastric artery by reducing “hunger” hormones from the gastric fundus is a procedure for weight loss that has been growing in prominence over the last several years, however, to date no randomized-controlled trial has been conducted until our study. We studied TBE in a double-blind, sham procedure, first in human RCT of patients (pts) with obesity. Purpose The purpose of this study was to assess the safety and efficacy of TBE for weight loss in obese patients as well as to evaluate metabolic changes. Methods After IV propofol, eligible pts (age 21–60; BMI 35–50 kg/m2) were randomized 1:1 to Sham (skin nick & 1 hr wait) or TBE. All pts received Lifestyle Therapy (behavioral and diet education). Study staff following the pts were also blinded to treatment. Blood samples for gastrointestinal hormones were collected in EDTA tubes containing a protease inhibitor cocktail and frozen per local laboratory standards. All collected samples were assessed together in two batches at the end of the study. The hormones analyzed included ghrelin, GIP, GLP-1, Visfatin, resistin, PAI-1 (total), Leptin, and C-Peptide. An Oral Glucose Tolerance Test (OGTT) and a diabetes assay was performed at baseline and at 6- and 12-months post-intervention. Note, while diabetes was an exclusion criterion for this study, pre-diabetes was not. Results 44 pts were enrolled, of which 40 pts were randomized equally to the groups, with no major complications in either group. TBE demonstrated superior weight loss over the control group at 6- and 12-months post-intervention in both intention-to-treat and per-protocol analyses. At 6 and 12 months, the TBE group demonstrated a clinically meaningful decrease in glucose 1-hour post-fasting by OGTT. GIP levels in the TBE group increased at a mean of 21%, indicative of an improvement in pre-diabetic milieu. Circulating plasma visfatin levels decreased 20% at 6 months and 26% at 12 months in the TBE group indicating a decrease in body fat. C-Peptide levels were noticeably increased in the TBE group at 6 months possibly indicating improvements in insulin sensitivity and beta-cell function. Conclusion(s) TBE is safe and results in clinically significant weight loss and demonstrated a positive effect on glucose homeostasis in pre-diabetic patients. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Endobar Solutions, LLC


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.


Author(s):  
Maria Gevezova ◽  
Danail Minchev ◽  
Iliana Pacheva ◽  
Yordan Sbirkov ◽  
Ralitsa Yordanova ◽  
...  

Background: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. Introduction: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using peripheral blood mononuclear cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. Method: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children was selected. Bioenergetic and metabolic studies of isolated PBMCs were performed with a Seahorse XFp analyzer. Result: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. Conclusion: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.


PEDIATRICS ◽  
1996 ◽  
Vol 98 (6) ◽  
pp. 1069-1075
Author(s):  
Janet R. Serwint ◽  
Modena E. H. Wilson ◽  
Judith W. Vogelhut ◽  
John T. Repke ◽  
Henry M. Seidel

Background. Prenatal pediatric visits have been recommended by the American Academy of Pediatrics to allow the pediatrician to counsel parents on infant care issues, establish a supportive relationship, and provide pediatric practice information to parents. We hypothesized that prenatal pediatric visits would have an impact on breastfeeding decisions, health care behaviors, health care utilization, and the doctor-patient relationship. Methods. We conducted a randomized controlled trial of prenatal pediatric visits for urban, low-income families to measure the impact on breastfeeding decisions, infant car safety seat use, circumcision, health maintenance, and emergency room visits and the pediatrician's perception that he/she would know the mother better. Pregnant women were recruited prenatally from the obstetrics clinic. Outcomes were measured by maternal interview prenatally and when the infant was 2 months old, in addition to review of the nursery record. Physicians were interviewed after the 2-month visit. Health care utilization was measured by chart review at 7 months. Results. A total of 156 pregnant women were enrolled and randomized, 81 to the intervention group and 75 to the control group. Of mothers who breastfed, 45% in the intervention group changed their mind in favor of breastfeeding after enrollment compared with 14% in the control group. Mothers in the intervention group compared with the control group were more likely to make fewer emergency room visits, 0.58 compared with 1.0. Pediatricians were more likely to think that they knew mothers in the intervention group well, 54% versus 29% in the control group, yet 67% of mothers in both groups agreed their pediatrician knew them well. There were no differences between groups in initiation or duration of breastfeeding at 30 or 60 days, infant car safety seat use, circumcision, or health maintenance visits. Conclusions. Prenatal pediatric visits have potential impact on a variety of health care outcomes. Among urban, low-income mothers, we found beneficial effects on breastfeeding decisions, a decrease in emergency department visits, and an initial impact on the doctor-patient relationship. We suggest urban practices actively promote prenatal pediatric visits.


2017 ◽  
Vol 9 (10) ◽  
pp. 253
Author(s):  
Luciano Fernandes Moura ◽  
Pedro Felipe Sousa Teixeira ◽  
Franklin Aragão Gondim ◽  
Francisco Holanda Nunes Junior ◽  
Rifandreo Monteiro Barbosa ◽  
...  

Biodigesters have been used to convert biomass into biogas and biofertilizers. This energy use has been important for the reduction of solid waste pollution in the environment. This work aims to analyse the viability of the use of pig biofertilizer produced by an Indian biodigester prototype, monitored by a data acquisition system. The biodigester used was an Indian prototype built on a low cost material that is easy to acquire (polyvinyl chloride-PVC). After the biofertilizer production, we tested its efficiency and viability under conditions of vegetation house in the cultivation of sunflower plants. The experimental design was completely randomized in a factorial arrangement with 4 concentrations of biofertilizer (0, 40, 80 and 120 kg N ha-1) × 4 harvest periods (14, 21, 25 and 29 days after sowing). We evaluated biometric and vigor parameters by measurements of stem diameter, height of the aerial part, number of leaves and production of fresh and dry matter of roots, aerial and total parts, as well as the relative chlorophyll content. We performed the experiment with five repetitions using two plants each and we submitted the data to analysis of variance (ANOVA) and polynomial regression using the statistical software Sisvar 5.4. The functional Indian biodigester prototype produced a biofertilizer of excellent quality and viability as a biofertilizer for the initial growth of sunflower plants. The biofertilizer served as a nutritional source in the sunflower crop, since it provided increases in all the growth parameters analyzed in relation to the control group (plants in the absence of biofertilizer), especially in the concentration of 120 kg N ha-1.


2017 ◽  
Vol 72 (3) ◽  
pp. 175-182 ◽  
Author(s):  
Humaira Naureen ◽  
Michel Feussi Tala ◽  
Khaled A. Shaaban ◽  
Mohamed Shaaban ◽  
Anja Schüffler ◽  
...  

Abstract Three new bioactive metabolites, 1,6-dihydroxy- 2-methyl-heptan-4-one (1), 4-hydroxy-1-(2-methyl-oxiranyl)- pentan-2-one (2), and 2-(2-hydroxy-propyl)-4-methylfuran- 3-carboxylic acid amide (3) were isolated from the terrestrial Streptomyces sp. isolate ANK245, along with the new microbial constituent p-vinylanisol (4a) and the known metabolites p-vinyl-phenol (4b) and phenethyl alcohol. Analysis of the nonpolar part of the extract by gas chromatography/mass spectrometry (GC-MS) provided further evidence for tetradecanoic acid, 9-octadecenoic acid, hexadecanoic acid, 2-methoxy-4-vinylphenol (4c), 4-hydroxy-3-methoxy-benzaldehyde, o-hydroxybiphenyl, and 1,5,9-trimethyl-4,8,13-cyclotetradecatrien-1,3-diol (5). Structures 1–3 of the new compounds were elucidated by nuclear magnetic resonance (NMR) and NMR spectroscopy, but mass spectrometry (MS) techniques and their absolute configuration were determined by density functional theory (DFT) calculations and Mosher derivatisation. Their antimicrobial and cytotoxic activities were evaluated in comparison with the crude bacterial extract.


2017 ◽  
Vol 35 (0) ◽  
Author(s):  
A. ALI ◽  
A. JAVAID ◽  
A. SHOAIB

ABSTRACT Sclerotium rolfsii is a soil-borne fungal plant pathogen that causes diseases in more than 500 plant species. Chemical fungicides used to control this disease cause environmental pollution, therefore, plant derived compounds can be used as alternative to synthetic fungicides to reduce environmental pollution. Chenopodium album is a weed of family Chenopodiaceae that is used as food and also has medicinal importance. In the present study, antifungal activity of methanolic root extract of C. album was evaluated against S. rolfsii using six concentrations viz. 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 g 100 mL-1 amended in malt extract as growth medium. All the root extract concentrations significantly reduced fungal biomass by 15-58% over control. Gas chromatography-mass spectrometry (GC-MS) analysis of the methanolic root extract of C. album was performed. Six compounds were identified in methanolic root extract through GC-MS analysis. The most abundant compound was 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester (58.56%) followed by 9-octadecenoic acid (Z)-, methyl ester (12.75%) and 9-octadecenoic acid (Z)-, methyl ester (10.27%), which might be responsible for antifungal activity of methanolic root extract of C. album.


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