Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial.
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ABSTRACT:
SUBMITTER: Kip P
PROVIDER: S-EPMC8621550 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR).BackgroundLifelong 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 reveal the pathways that are modulated by short-term CR, which are associated with protection of the mouse heart from ischemia.MethodsMale 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 for 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. At d8, the left ventricles (LV) of AL and CR mice were collected for Western blot, mRNA and microRNA (miR) analyses to identify cardioprotective gene expression signatures. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI.ResultsThis 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). mRNA 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). CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.
| S-EPMC4476723 | biostudies-literature
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: Not available
| S-EPMC9842083 | biostudies-literature
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: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.
2015-12-31 | GSE60596 | GEO
Project description:White adipose tissue (WAT) hypertrophy is an essential hallmark of obesity and is associated with the activation of resident immune cells. While the benefits of caloric restriction (CR) on health span are generally accepted, its effects on WAT physiology are not well understood. We previously demonstrated that short-term CR reverses obesity in male rhesus macaques exposed to a high-fat Western-style diet (WSD). Here, we analyzed subcutaneous WAT biopsies collected from this cohort of animals before and after WSD and following CR. This analysis showed that WSD induced adipocyte hypertrophy and inhibited ?-adrenergic-simulated lipolysis. CR reversed adipocyte hypertrophy, but WAT remained insensitive to ?-adrenergic agonist stimulation. Whole-genome transcriptional analysis revealed that ?3-adrenergic receptor and de novo lipogenesis genes were downregulated by WSD and remained downregulated after CR. In contrast, WSD-induced pro-inflammatory gene expression was effectively reversed by CR. Furthermore, peripheral blood monocytes isolated during the CR period exhibited a significant reduction in the production of pro-inflammatory cytokines compared to those obtained after WSD. Collectively, this study demonstrates that short-term CR eliminates an obesity-induced pro-inflammatory response in WAT and peripheral monocytes.
| S-EPMC7071433 | biostudies-literature
Project description:While weight loss is highly recommended for obesity, promoting inflammation resolution, >80% of those who lose weight will regain it back, resulting in worsening of disease outcomes (including cardiovascular disease), relative to never having lost weight. However, how weight loss and regain directly influence atherosclerotic inflammation was unknown and investigated in this stud. Using short-term caloric restriction (stCR) in obese mice, we found that weight loss promotes atherosclerosis resolution, independently of plasma cholesterol. Mechanistically, we found that this is partly attributed to a unique subset of macrophage, distinguished by high expression of the antibody receptor Fcgr4, that accumulated in epididymal adipose tissue and plaques with stCR and help to clear necrotic cores. Interestingly, our data suggest that eWAT-derived Fcgr4 macrophages contribute to the clearance of plaque necrotic cores. On the other hand, weight regain achieved by ab libitum feeding following the stCR phase resulted in acceleration of atherosclerosis progression and disappearance of Fcgr4 macrophages from both adipose and plaques. Furthermore, weight regain caused inflammatory reprogramming of bone marrow immune progenitors, retaining hyper-inflammatory capabilities for long periods thereafter.
2024-02-09 | GSE225077 | GEO
Project description:Obesity is highly prevalent, causing substantial cardiovascular and mental health morbidity. Women show increased risk for mental health disorders, that is multiplied in obesity and related to cellular and psychological stress that can be targeted by non-pharmacological interventions. A total of 43 women underwent two weeks of caloric restriction, half of which also received 7 h of individualized clinical psychological intervention including psychoeducation, mindfulness, and heart-rate-variability biofeedback. Effects on body mass index (BMI), fatty liver index (FLI), bioimpedance measures, serum parameters, perceived stress (PSS), burn-out susceptibility (burn out diagnostic inventory) and dimensional psychiatric symptom load (brief symptom inventory, BSI) were analyzed with linear mixed effects models. Caloric restriction led to a reduction in BMI, body fat and FLI, decreased serum concentrations of leptin, PSS score, BSI dimensions and global severity index (all p ≤ 0.0001, withstanding Bonferroni-Holm correction). Benefits of add-on biofeedback were observed for BMI reduction (p = 0.041). Caloric restriction was effective in ameliorating both psychological wellbeing and metabolic functions following a BMI reduction. Biofeedback boosted effects on BMI reduction and the combinative therapy may be protective against common progression to mental health and cardiovascular disorders in overweight women while comparing favorably to pharmacological interventions in terms of side-effects and acceptability.
| S-EPMC8623687 | biostudies-literature
Project description:BackgroundAn ageing population has resulted in a rise in the number of hip and knee replacement surgeries in the UK. The pre-operative pathway is plagued with issues causing long delays and cancellations. Virtual healthcare technologies have a growing evidence base to help solve these issues. One problem of implementing these technologies is the resistance to change mentality from healthcare professionals. By getting their opinions on the place of these technologies within the pre-operative pathway, a united front can be formed to help deliver change.MethodsSixteen semi-structured interviews were conducted with key stakeholders within the orthopaedic pre-operative pathway at Imperial College Healthcare NHS Trust. General topics included the different technologies that could be used within the pathway, their uses and associated benefits and problems. Interviews were audio-recorded, before being manually transcribed and then analysed to form categories and themes.ResultsVarious uses, benefits and problems were identified by healthcare professionals for each modality of technology. E-forms were seen as a high reward, low-risk intervention. Remote patient monitoring and teleconsultations had their bonuses, but feasibility was a primary concern. Web-based interventions were seen as an intervention of the past, whereas virtual reality was seen as perhaps being ahead of its time. M-health was very positively viewed due to its all-encompassing nature. Digital illiteracy emerged as a consistent problem for most technologies.ConclusionsCurrent literature, the results from this study and technology trends within society highlight both M-health and E-forms as the 2 most promising virtual healthcare technologies for use in the pre-operative pathway for orthopaedics. Areas such as pre-operative assessment, triaging and prehabilitation are prime candidates for virtual intervention. Future research should also consider including patient opinions on any proposed interventions, as well as taking into account barriers to implementation.
| S-EPMC7667783 | biostudies-literature