Rapid remodeling of the human gut microbiome in response to short-term animal product restriction
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PROVIDER: PRJEB94951 | ENA |
REPOSITORIES: ENA
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Project description:OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia. METHODS: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1?, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR. . Male 12 wk-old C57Bl/6 mice were obtained from Charles River (Montreal, PQ, Canada) and maintained for at least 2 weeks before experimentation. Animals were randomly assigned to AL, CR and Lira groups with no initial differences in body weights. AL group mice were allowed ad libitum diet. Lira group mice were injected with Liraglutide (Glucagon-like peptide-1 agonist) at a dose of 200 µg/Kg i.p., twice daily for 7 days which is a mild weight-loss inducing dose and had access to ad libitum food and water. CR group mice were put on a Caloric restriction diet (30% less than normal ad libitum caloric intake) for 7 days to induce weight loss comparable to Lira group mice. Mice for CR and AL were individually caged and their food intake was measured everyday between 10-11 am for 1 week to calculate the average daily food intake. CR mice were fed 30% less than the calculated mean daily AL food consumption. CR cages were inspected daily for any remaining food, and transferred to a new cage every day. For CR group, pre-weighed mouse chow pellets were placed in cages between 10-11 am every day. Body weights were recorded between 10-11 am before and after the 7 day study period. For pre-ischemic assessments, animals (n=5/group/assessment) were sacrificed on day-8 (pre-MI), hearts were immediately extracted, washed in sterile phosphate-buffered saline (PBS), with LV free walls dissected, snap frozen in liquid nitrogen and stored at -80o C.
2015-05-08 | E-GEOD-68646 | biostudies-arrayexpress
Project description:OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia. METHODS: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR. .
2015-05-08 | GSE68646 | GEO
Project description:Caloric restriction increases life-span of a number of organisms. The relationship between the increase in life-span and the extent of caloric restriction, however, varies among species. The underlying mechanisms are yet unknown, but appear to be related to changes in metabolism. In order to investigate the metabolic response of caloric restriction of rats, here is presented the first nuclear magnetic resonance (NMR) spectroscopy-based study of how blood metabolite profiles are influenced by graded levels of caloric restriction. The study involved three groups of obese rats exposed to 0, 20, and 40% caloric restriction for five days. Blood serum from each individual was analyzed by 1H NMR and the resulting spectra were subjected to multivariate analysis by unsupervised principal component analysis and supervised orthogonal-partial least square discriminant analysis. The analyzes revealed that a response to caloric restriction was present at 20% caloric restriction. The metabolites that distinguished the profiles at 20% restriction deviated from those at 40% restriction. The changes induced by caloric restriction were most clearly observed as an increased level of 3-hydroxybutyrate, and decreased levels of lipids and pyruvate. The metabolic responses of rats exposed to caloric restriction are in good agreement with a switch in metabolism from anabolic pathways towards fatty acid catabolism and gluconeogenesis, which is consistent with previous observations for mice.
2014-09-05 | MTBLS114 | MetaboLights
Project description:Analysis of the transcriptome in the epididymal fat of young mice (8 months of age) from treatment of dietary restriction, or rapamycin Total RNA extracted from epididymal fat of 8 month old C57BL6/J mice started on ad libitum (AL) , 40% dietary restriction (DR), or 14 ppm rapamycin (Rapa) from 2 months of age on 6 months of treatment. Number of samples total: 24, with 8 samples in AL, 8 samples in DR, and 8 samples in Rapa
2014-08-18 | E-GEOD-52825 | biostudies-arrayexpress
Project description:To provide a robust understanding of a transcriptomic change by short-term CR at body fat of mice, we applied three serial strengths of CR to mice including 15%, 30%, and 45% reduction of carbon source. Using Affymetrix mouse 1.0 ST array platform, we obtained and analyzed the transcriptome data for significantly changed genes in expression. Here, we identified 446 genes and categorized the genes based on their biological roles. We observed gradual down-regulation of several signaling pathways including insulin/insulin-like growth factor (IGF) 1, epidermal growth factor (EGF), transforming growth factor beta (TGF-β) and canonical Wingless-type mouse mammary tumor virus integration site (Wnt) signaling according to the CR strengths. Many genes related to structural feature including extracellular matrix (ECM), cell adhesion and cytoskeleton were also down-regulated with a strong correlation to the serial CR treatments. Furthermore, genes for cell cycle and adipogenesis were down-regulated. According to previous studies, these are target functions of the aforementioned four signaling pathways. On the other hand, the genes for specific metabolic features including tricarboxylic acid (TCA) cycle and electron transport chain (ETC) exhibited a transcriptional increase. In addition, adipose tissue expansion markers such as leptin, Mesoderm specific transcript (Mest) and Secreted frizzled-related sequence protein 5 (Sfrp5), and most genes for transport and immune response showed a down-regulation by CR. Comparing gene expression profiles to understand transcriptomic changes of adipose tissue by serial strength (15%, 30%, and 45%) of short-term (10 weeks) caloric restriction to young age (18 weeks) mice (n=3 in each group).
2015-12-31 | E-GEOD-60596 | biostudies-arrayexpress
Project description:Chronic caloric restriction (CR) and rapamycin inhibit the mechanistic target of rapamycin (mTOR) signaling, thereby regulating metabolism and suppressing protein synthesis. Caloric restriction or rapamycin extends murine lifespan and ameliorates many aging-associated disorders; however, the beneficial effects of shorter treatment on cardiac aging are not as well understood. Using a recently developed deuterated-leucine labeling method, we investigated the effect of short-term (10 weeks) CR or rapamycin on the proteomics turnover and remodeling of the aging mouse heart. Functionally, we observed that short-term CR and rapamycin both reversed the pre-existing age-dependent cardiac hypertrophy and diastolic dysfunction. There was no significant change in the cardiac global proteome (823 proteins) turnover with age, with a median half-life 9.1 days in the 5-month-old hearts and 8.8 days in the 27-month-old hearts. However, proteome half-lives of old hearts significantly increased after short-term CR (30%) or rapamycin (12%). This was accompanied by attenuation of age-dependent protein oxidative damage and ubiquitination. Quantitative proteomics and pathway analysis revealed an age-dependent decreased abundance of proteins involved in mitochondrial function, electron transport chain, citric acid cycle, and fatty acid metabolism as well as increased abundance of proteins involved in glycolysis and oxidative stress response. This age-dependent cardiac proteome remodeling was significantly reversed by short-term CR or rapamycin, demonstrating a concordance with the beneficial effect on cardiac physiology. The metabolic shift induced by rapamycin was confirmed by metabolomic analysis.
| S-EPMC4040127 | biostudies-literature
Project description:Analysis of the transcriptome in the epididymal fat of young mice (8 months of age) from treatment of dietary restriction, or rapamycin
2014-08-18 | GSE52825 | GEO
Project description:Anti-angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit is limited, urging the improvement of combination therapies. We aimed to clarify the effects of vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration of drugs in esophagogastric adenocarcinoma (EAC). Patient-derived xenograft (PDX) models of EAC were subjected to long-term and short-term treatment with anti-VEGFR2 therapy followed by chemotherapy injection or multi-agent dynamic contrast-enhanced (DCE-) MRI and vascular casting. Long-term anti-VEGFR2-treated tumors showed a relatively lower flow and vessel density resulting in reduced chemotherapy uptake. On the contrary, short-term VEGFR2 targeting resulted in relatively higher flow, rapid vasodilation, and improved chemotherapy delivery. Assessment of the extracellular matrix (ECM) revealed that short-term anti-angiogenic treatment drastically remodels the tumor stroma by inducing nitric oxide synthesis and hyaluronan degradation, thereby dilating the vasculature and improving intratumoral chemotherapy delivery. These previously unrecognized beneficial effects could not be maintained by long-term VEGFR2 inhibition. As the identified mechanisms are targetable, they offer direct options to enhance the treatment efficacy of anti-angiogenic therapy combined with chemotherapy in EAC patients.
| S-EPMC7138404 | biostudies-literature