Analysis of differential genetic expression by moderate-carbohydrate restriction diet with calorie restriction mimetic multiple phytochemicals (MCDmp) using a transgenic liver cancer model developed by a simple hydrodynamic transfection method.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37762 | GEO | 2012/05/05
SECONDARY ACCESSION(S): PRJNA163323
REPOSITORIES: GEO
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Project description:We performed survival analysis of control and MCD groups, and explored underlying tumor suppression mechanisms after dietary intervention, focused on alterations in the energy-dependent signaling pathways, histone modifications, and global gene expression differences on cDNA microarray study. Five- week- old male C57BL6 mice were randomly divided into two groups and fed control diet (control group, LabDiet, Brentwood, MO, USA) or moderate restriced carbohydrate diet formula (MCD, Treat group) in a specific pathogen free zone. All procedures were approved by the institutional animal use and care committee. Following a preliminary feeding of each diet formula for two week, HrasG12V / shp53 / GFP4 gene containing transposon vector were injected into mouse tail vein by hydrodynamic injection method. After 4 weeks of diet supplementation, all mice were sacrificed. Mouse liver tissue was excised for microarray analysis.
2012-05-04 | E-GEOD-37762 | biostudies-arrayexpress
Project description:We performed survival analysis of control and MCDmp groups, and explored underlying tumor suppression mechanisms after dietary intervention, focused on alterations in the energy-dependent signaling pathways, and global gene expression differences on cDNA microarray study, or histone modification on ChIP-on-chip analysis.
2012-03-21 | GSE36633 | GEO
Project description:Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat.
| S-EPMC4603544 | biostudies-literature
Project description:Study objectivesThis study examined how glucose, glucose regulatory hormones, insulin sensitivity, and lipoprotein subclass particle concentrations and sizes change with sleep restriction during weight loss elicited by calorie restriction.MethodsOverweight or obese adults were randomized into an 8-week calorie restriction intervention alone (CR, n = 12; 75% female; body mass index = 31.4 ± 2.9 kg/m2) or combined with sleep restriction (CR+SR, n = 16; 75% female; body mass index = 34.5 ± 3.1 kg/m2). Participants in both groups were given the same instructions to reduce calorie intake. Those in the CR+SR group were instructed to reduce their habitual time-in-bed by 30-90 minutes 5 days each week with 2 ad libitum sleep days. Fasting venous blood samples were collected at pre- and post-intervention.ResultsDifferential changes were found between the two groups (p = 0.028 for group × time interaction) in glucagon concentration, which decreased in the CR group (p = 0.016) but did not change in CR+SR group. Although changes in mean HDL particle (HDL-P) size and visfatin concentration were not statistically different between groups (p = 0.066 and 0.066 for group×time interaction, respectively), mean HDL-P size decreased only in the CR+SR group (Cohen's d = 0.50, p = 0.022); visfatin concentrations did not change significantly in either group but appeared to decrease in the CR group (Cohen's d = 0.67, p = 0.170) but not in the CR+SR group (Cohen's d = 0.43, p = 0.225).ConclusionThese results suggest that moderate sleep restriction, despite the presence of periodic ad libitum sleep, influences lipoprotein subclass particles and glucose regulation in individuals undergoing calorie restriction.Clinical trial registration: ClinicalTrials.gov (NCT02413866, Weight Outlooks by Restriction of Diet and Sleep).
| S-EPMC7898726 | biostudies-literature
Project description:The impact of moderate calorie restriction on reproductive neuroendocrine function was investigated in young adult male rhesus macaques (Macaca mulatta). The animals were subjected to either 30% calorie restriction (CR; n=5), or were fed a standard control diet (CON; n=5), starting during their peripubertal period. Plasma LH and testosterone concentrations were examined after 7 years of differential dietary treatment, and were found to be similar in both groups, both during the day and during the night. Microarray profiling of pituitary gland and testicular gene expression was performed after 8 years of treatment, using GeneChip® Rhesus Macaque Genome Arrays (Affymetrix), and showed very little effect of caloric restriction. Using a 1.5-fold difference threshold, our microarray analysis revealed differential expression of only 145 probesets in the pituitary gland and 260 in the testes, out of a total of >54,000. Semi-quantitative RT-PCR performed on pituitary gland mRNA corroborated the microarray findings for selected modulated genes, including TSH receptor (TSHR) and sperm-specific antigen 2 (SSFA2). Most notably, significantly lower expression of TSH receptor mRNA was observed in the pituitary of CR compared to CON animals. Also, significantly lower expression of the glycoprotein hormone alpha subunit (CGA) was observed in CR animals, and this finding was further corroborated using quantitative real-time RT-PCR. No significant diet-induced changes were detected in the testis for genes associated with reproduction, circadian clocks, or oxidative stress. There is mounting evidence that CR may promote health and longevity in a wide range of organisms, including nonhuman primates. Importantly, our data suggest that moderate CR has no obvious lasting detrimental effect on the reproductive neuroendocrine axis of long-lived primates, and has only a modest influence on pituitary and testicular gene expression.
| S-EPMC2929798 | biostudies-literature
Project description:BackgroundCalorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional activity of intermittent CR vs continuous CR in metabolic disorders such as diabetes.MethodsIn this study, we analyzed two protocols of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2-5 or 5-9 regimes followed by free eating for 5 or 9 days respectively).ResultsIn the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models.ConclusionsOur study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving glucose homeostasis in db/db mice.
| S-EPMC6714240 | biostudies-literature
Project description:Calorie restriction (CR) enhances health span (the length of time that an organism remains healthy) and increases longevity across species. In mice, these beneficial effects are partly mediated by the lowering of core body temperature that occurs during CR. Conversely, the favorable effects of CR on health span are mitigated by elevating ambient temperature to thermoneutrality (30°C), a condition in which hypothermia is blunted. In this study, we compared the global metabolic response to CR of mice housed at 22°C (the standard housing temperature) or at 30°C and found that thermoneutrality reverted 39 and 78% of total systemic or hypothalamic metabolic variations caused by CR, respectively. Systemic changes included pathways that control fuel use and energy expenditure during CR. Cognitive computing-assisted analysis of these metabolomics results helped to prioritize potential active metabolites that modulated the hypothermic response to CR. Last, we demonstrated with pharmacological approaches that nitric oxide (NO) produced through the citrulline-NO pathway promotes CR-triggered hypothermia and that leucine enkephalin directly controls core body temperature when exogenously injected into the hypothalamus. Because thermoneutrality counteracts CR-enhanced health span, the multiple metabolites and pathways altered by thermoneutrality may represent targets for mimicking CR-associated effects.
| S-EPMC7580877 | biostudies-literature
Project description:BackgroundObesity is a growing global public health problem. It has been associated with diabetes, cardiovascular disease, cancer, and an increased risk of all-cause mortality, as well as infertility. Calorie restriction (CR) is an effective life intervention to defend against obesity. This study aimed to investigate the effects of long-term moderate CR on the reproductive function and underlying mechanisms in a mouse model of obesity.MethodsMale C57BL/6 mice were randomized to two groups receiving either a standard diet (STD) or a high-fat diet (HFD) for 8 weeks to induce obesity. The HFD-induced obesity mice were further randomized into two groups: HFD group and CR group (reduced the mean amount of HFD by 25%). After 12 weeks, the body weight, testicular coefficients, fasting blood glucose (FBG), serum triglyceride (TG), and total cholesterol (TC) were detected and measured. The sperm quality was detected by an automatic sperm quality analyzer (SQA-V). The structure of testicular tissues was examined by hematoxylin and eosin (HE) staining. Testicular cell apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The levels of NAD-dependent deacetylase sirtuin-1 (SIRT1) and antioxidative enzymes were detected in the testes.ResultsCR treatment reduced weight gain and increased testicle coefficients in HFD-induced obese mice. CR reduced the serum level of FBG, TG, and TC, and increased the serum levels of testosterone. Moreover, CR increased sperm count and motility, and sperm normality in obese mice. Furthermore, CR ameliorated the testicular morphological damage and cell apoptosis in obese mice. CR also attenuated the oxidative stress level and increased the protein expressions of SIRT1 in testicular tissues of obese mice.ConclusionsLong-term moderate CR improves obese male fertility, probably by alleviating oxidative stress via activation of SIRT1 signaling.
| S-EPMC8263864 | biostudies-literature
Project description:We previously reported that moderate calorie restriction (CR) has minimal impact on testicular gene expression in young adult rhesus macaques, and no obvious negative impact on semen quality or plasma testosterone levels. We now extend these findings by examining the influence of CR on various aspects of the reproductive axis of older males, including 24-h circulating testosterone levels, testicular gene expression, and testicular morphology. Young adult and old adult male rhesus macaques were subjected to either 30 % CR for 5-7 years, or were fed a standard control diet. Analysis of the 24-h plasma testosterone profiles revealed a significant age-associated decline, but no evidence for CR-induced suppression in either the young or old males. Similarly, expression profiling of key genes associated with testosterone biosynthesis and Leydig cell maintenance showed no significant CR-induced changes in either the young or old animals. The only evidence for CR-associated negative effects on the testis was detected in the old animals at the histological level; when old CR animals were compared with their age-matched controls, there was a modest decrease in seminiferous tubule diameter and epithelium height, with a concomitant increase in the number of depleted germ cell lines. Reassuringly, data from this study and our previous study suggest that moderate CR does not negatively impact 24-h plasma testosterone profiles or testicular gene expression. Although there appear to be some minor CR-induced effects on testicular morphology in old animals, it is unclear if these would significantly compromise fertility.
| S-EPMC3889886 | biostudies-literature
Project description:An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA. We showed before that suppression of LIP in mice, reflecting reduced mTORC1-signaling at the C/EBPβ level, results in CR-type of metabolic improvements. Hence, we aim to find possibilities to pharmacologically down-regulate LIP in order to induce CR-mimetic effects. We engineered a luciferase-based cellular reporter system that acts as a surrogate for C/EBPβ-mRNA translation, emulating uORF-dependent C/EBPβ-LIP expression under different translational conditions. By using the reporter system in a high-throughput screening (HTS) strategy we identified drugs that reduce LIP. The drug Adefovir Dipivoxil passed all counter assays and increases fatty acid β-oxidation in a hepatoma cell line in a LIP-dependent manner. Therefore, these drugs that suppress translation into LIP potentially exhibit CR-mimetic properties.
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