Transcription profiling of peripheral blood mononuclear cells from over weight human subjects before and after a low calorie diet
Ontology highlight
ABSTRACT:
INSTRUMENT(S): GenePix Personal 4100A [Axon Instruments]
ORGANISM(S): Homo sapiens
SUBMITTER: Javier Margareto
PROVIDER: E-MEXP-1055 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown and the involvement of the TOR and Sirtuin pathways (which regulate aging in lower organisms) remain controversial. Femaleness is a second phenotype generally associated with longevity but the relationship between sex-biased and CR-induced gene expression remains undetermined. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the Sirtuin pathway. Using Western analyses, we confirmed post-translational inhibition of the TOR pathway. Conclusions: Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of the longer-lived female sex. Keywords: Two-class gene expression comparison. Calorie restriction (CR) versus HIGH CALORIE feeding. Design of the experiment is a two-class paired design in which the two classes are HIGH CALORIE and CALORIE RESTRICTION (CR) dietary regimens fed to mice, resulting in 15 HIGH CALORIE microarrays and 8 CR microarrays; 23 total microarrays. Four HIGH CALORIE and 2 CR microarrays were produced using pools of 3 RNA samples for each microarray (6 pools of 3, plus 17 individual samples = 35 individual mouse liver samples, 23 microarrays). Total liver RNA was labeled directly. Reference RNA: Stratagene Universal Mouse Reference RNA.
2008-12-30 | E-GEOD-11244 | biostudies-arrayexpress
Project description:Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Caloric restricted mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed significantly fewer TUNEL-positive staining cells and fewer cleaved caspase-3-positive staining cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 28 proapoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR or staying lean can retard this process by suppressing apoptosis in the inner ear tissue. Experiment Overall Design: To examine the effects of aging, a comparison of cochlea tissues from YC (3 samples) and MC (3 samples) mice was conducted. To examine the effects of calorie restriction (CR), a comparison of cochleae from MC (3 samples) and CR (3 samples) mice was conducted. We examined age-related changes in gene expression in the cochlea and calorie restriction-induced changes in gene expression in the cochlea. We pooled four cochleae from two mice for one sample and used three samples per group (n = 3). Quality control measures were not used. No replicates were done. Dye swap was not used.
2007-11-22 | E-GEOD-4786 | biostudies-arrayexpress
Project description:We wanted to investigate the impact of macronutrient composition on blood gene expression in obese men and relate it to low-grade systemic inflammation and onset of lifestyle diseases. Additionally, we wanted to compare blood cell gene expression pattern with subcutaneous adipose tissue cell gene expression pattern. The current study was designed as a pilot to a more comprehensive main study (manuscript in preparation). We wanted to gain experience to optimize sample size, diet intervention length, tissue for gene expression analysis, and the type of food to be used for diet intervention in the main study. Three final gene expression matrices are provided for this study. The first is a 3 persons x 6 time points blood cell RNA hybridizations (time profiling of blood cell gene expression). The second is blood cell RNA hybridizations normalized and the third is adipose tissue cell RNA hybridizations normalized.
2010-10-15 | E-MEXP-2779 | biostudies-arrayexpress
Project description:Resveratrol has been reported to improve metabolic function in metabolically-abnormal rodents and humans, but has not been studied in non-obese people with normal glucose tolerance. We conducted a randomized, double-blind, placebo-controlled trial to evaluate the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in non-obese, postmenopausal women with normal glucose tolerance. Although resveratrol supplementation was well-tolerated and increased plasma resveratrol concentration without adverse effects, it did not change body composition, resting metabolic rate, plasma lipids, or inflammatory markers. A two-stage hyperinsulinemic-euglycemic clamp procedure, in conjunction with stable isotopically-labeled tracer infusions, demonstrated that resveratrol did not increase liver, skeletal muscle, or adipose tissue insulin sensitivity. Consistent with the absence of in vivo metabolic effects, resveratrol did not affect its putative molecular targets, including AMPK, Sirt1, Nampt, and Pgc-1α, in either skeletal muscle or adipose tissue. These findings demonstrate that resveratrol supplementation does not have metabolic effects in non-obese women. We compared gene expression profile in subcutaneous abdominal adipose tissue and skeletal muscle (vastus lateralis) biopsy samples obtained from non-obese people before and after 1) placebo (PLC), 2) resveratrol (RES), and 3) calorie restriction (CR) intervention.
2013-01-02 | E-GEOD-41168 | biostudies-arrayexpress
Project description:Obesity and associated increased prevalence of non-alcoholic fatty liver (NAFLD) disease is suggested to be positively modulated by a high protein (HP) diet in humans and rodents. The aim was to detect mechanisms by which a HP diet prevents hepatic lipid accumulation by means of transcriptomics. To study the acute and long term effect of a high protein ingestion on hepatic lipid accumulation under both low and high fat (HF) conditions, mice were fed combinations of high (35%) or low (10%) fat and high (50%) or normal (15%) protein diets for 1 or 12 weeks. Body composition, liver fat, VLDL production rate and gene expression were investigated. Differences in metabolic processes and functions in the liver were identified using gene set enrichment analysis on microarray data. Mice fed the HP diets developed less adiposity and decreased hepatic lipid accumulation due a combination of induced processes mainly involved in protein catabolism such as transamination, TCA cycle and oxidative phosphorylation. Feeding a HP diet can successfully prevent the development of NAFLD by using ingested energy for oxidation instead of storage. Wild type mice were fed combinations of high (35%) or low (10%) fat and high (50%) or normal (15%) protein diets for 1 or 12 weeks. After the diet intervention period, the animals were killed and liver tissue was removed. Total RNA was isolated, pooled and subjected to gene expression profiling.
2012-11-21 | E-GEOD-37897 | biostudies-arrayexpress
Project description:The present study was designed to identify determinants that foreshadow successful weight maintenance. More specifically, we examined whether subcutaneous adipose tissue (scAT) gene expression of participants who experience successful weight maintenance following caloric restriction differed from that of participants who regain weight. Forty women followed a dietary protocol consisting of an 8-week low calorie diet (LCD) and a 6-month weight maintenance phase. At the end of the protocol, participants were classified as weight maintainers (WM; 0-10% weight regain) and weight regainers (WR; 50-100% weight regain). Anthropometric measurements, plasma parameters, and scAT biopsies were taken before and after the LCD. Adipose tissue gene expression profiles were studied in all individuals before and after the LCD.
2011-09-29 | E-GEOD-24432 | biostudies-arrayexpress
Project description:Gene expression studies in peripheral blood mononuclear cells (PBMC) can provide knowledge that would be difficult to obtain using other types of biological samples, as these cells can reflect overall response of the body to a specific stimulus, such as diet. Here, we aimed to study the impact of sustained intake of isocaloric diets with an unbalanced macronutrient proportion (rich in fat or protein) on PBMC gene expression in rats using transcriptomics, to better understand the effects of these diets on metabolism and health. Macronutrient diet composition (especially increased protein content) affected PBMC gene expression. An important effect was observed in immune response-related genes. High protein (HP) diet produced an activation of genes mainly related to antigen recognition/presentation, whereas the high fat (HF) diet was more related to a decreased expression of these genes. Key energy homeostasis genes (mainly involved in lipid metabolism) were also affected, reflecting a nutritional adaptive response to the diets. Decreased Dhrs3 and increased Pref-1/Dlk1 expression observed in HP-fed animals reflects a lower lipogenic capacity. In addition, HF diet affected the expression of genes related to insulin resistance/signaling (Msra/Slc9a6, Asb6), hypoxia (Akap12), cardiovascular problems (Ethe1, Lr11), cognitive impairment (Tmcc2) and tumorigenesis (Ddx17, Phb, Rnasen/Drosha, and Tsc2). HP diet also impaired the expression of genes related to glucose metabolism and insulinemia (Glut-4/Slc2a4, Sfxn5, Slc16a1), but positively affected genes involved in liver function (Clec4f and St6galnac3) and cardiovascular protection (Sort1). In conclusion, gene expression analysis in PBMC can provide information that could be useful to detect metabolic deviations and health consequences of diets with an unbalanced macronutrient composition. 2 months-old male Wistar rats received a low fat control diet, or a high fat (HF) diet, or a high protein (HP) diet for 4 months, respectively. At the end of the intervention, prior to the sacrifice of the animals, peripheral blood samples (1.5-2.5 mL) were collected from the safena vein, using heparin in NaCl (0.9%) as anticoagulant. Immediately after blood collection, peripheral blood mononuclear cells (PBMC) were isolated by Ficoll gradient separation. Total RNA was isolated from PBMC, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 4x44K microarrays.
2015-12-07 | E-GEOD-54897 | biostudies-arrayexpress
Project description:Adult female Wistar rats (about 220g) obtained from a breeding colony were mated and fed either a protein sufficient (PS) or protein restricted (PR) diet (n = 6 per dietary group) during F0 pregnancy which provided an increase in energy of approximately 25% compared to the diet fed to the breeding colony (2018S). During lactation dams were fed AIN93G and litters were standardisied to 8 offspring within 24 hours of birth with a bias towards females. Offpsring were weaned onto AIN93M at postnatal day 28 and F1 and F2 females were mated on postnatal day 70 (n = 6 per F0 dietary group). F1 and F2 dams were fed the PS diet during pregnancy and AIN93G during lactation. Offspring were weaned onto AIN93M. On postnatal day 70 unmated female offspring were fasted for 12 hours then sacrificed for hepatic transcritpome analysis by microarray. Expression of 1,684 genes differed by at least 2 fold between adult female F1 offspring of F0 dams from both dietary groups. 1680 genes were altered in F2 offspring and 2,065 genes altered in F3 offspring. Expression of 113 genes was altered in all three generations. Of these, 47% showed directionally opposite differences between generations. Gene ontology analysis revealed clear differences in the pathways altered in each generation. F1 and F2 offspring of F0 dams fed a PR diet showed impaired fasting glucose homeostasis. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) expression was elevated in F1 and F2 offspring from F0 PR dams, but decreased in F3, compared to PS offspring
2011-06-01 | E-MEXP-3205 | biostudies-arrayexpress
Project description:Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems. Keywords: Expression profiling by array Mice received a control diet, or a diet supplemented with 10% dietary fibers for 10 days. After an overnight fast colon was removed, epithelial cells were scraped off, and subjected to gene expression profiling.
2015-05-26 | E-GEOD-59494 | biostudies-arrayexpress
Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cellsâ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways. Gene expression was profiled in peripheral blood mononuclear cells (PBMCs) from young and old men before and after 30% caloric restriction.
2016-10-24 | E-GEOD-63117 | biostudies-arrayexpress