Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance.
PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity.
Sex, Age, Time
View SamplesPolyphenolic compounds, such as resveratrol, have recently received widespread interest due to their ability to mimic effects of calorie restriction. The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology and underlying processes. Nine healthy obese men were supplemented with placebo and 150mg/day resveratrol for 30 days, separated by a 4-week washout period. A postprandial abdominal subcutaneous adipose tissue biopsy was collected to assess adipose tissue morphology and gene expression using microarray analysis. Resveratrol significantly decreased adipocyte size, with a shift towards a reduction in the proportion of large and very large adipocytes and an increase in small adipocytes. Microarray analysis revealed downregulation of Wnt, Notch and BMP/TGF- signaling pathways and upregulation of pathways involved in cell cycle after resveratrol supplementation, suggesting enhanced adipogenesis. Furthermore, the lysosomal/phagosomal pathway and the transcription factor EB were upregulated, reflecting an alternative pathway of lipid breakdown by autophagy. These data suggest that adipose tissue is an important target tissue for the effects of resveratrol in humans, but further research is necessary to investigate whether it translates into an improved adipose tissue function.
The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men.
Sex, Age, Specimen part, Disease, Treatment, Race, Subject
View SamplesThe effects of freeze-dried tofu, a traditional Japanese soy food, were compared with those of major active soy components, protein and isoflavone, by observing physiological differences and global transcriptomes in the liver of male rats.
Tofu (soybean curd) lowers serum lipid levels and modulates hepatic gene expression involved in lipogenesis primarily through its protein, not isoflavone, component in rats.
Sex, Specimen part
View SamplesMalignant melanoma is a complex genetic disease and the most aggressive form of skin cancer. Melanoma progression and metastatic dissemination fundamentally relies on the process of angiogenesis. Melanomas produce an array of angiogenic modulators that mediate pathological angiogenesis. Such tumor-associated modulators arbitrate the enhanced proliferative, survival and migratory responses exhibited by endothelial cells, in the hypoxic tumor environment. The current study focuses on melanoma-induced survival of endothelial cells under hypoxic conditions. Melanoma conditioned media were capable of enabling prolonged endothelial cell survival under hypoxia, in contrast with the conditioned media derived from melanocytes, breast and pancreatic tumors. To identify the global changes in gene expression and further characterize the pro-survival pathway induced in endothelial cells, we performed microarray analysis on endothelial cells treated with melanoma conditioned medium under normoxic and hypoxic conditions.
Melanomas prevent endothelial cell death under restrictive culture conditions by signaling through AKT and p38 MAPK/ ERK-1/2 cascades.
Specimen part
View SamplesData accompaning to van Gurp et al. Development 2019. single-cell sequencing of the developing mouse pancreas followed by Seurat analysis to discover genes important for alpha and beta cell differentiation. Overall design: Single-cells from mouse embryonic pancreas at E12.5, E13.5, E14.5, E15.5 and E18.5 were isolated and enriched for MIP-GFP and sorted into 384-well plates. Afterwards, SORT-seq was performed and single-cell transcriptomics profiles were obtained.
A transcriptomic roadmap to α- and β-cell differentiation in the embryonic pancreas.
Subject
View SamplesDorsomorphin is a small molecule inhibitor of type I bone morphogenic protein receptors (BMPRs). We have found that dorsomorphin affects a wide range of T cell function. In order to obtain the bigger picture of the effects of DM in T cell activation. transcriptomic analysis was performed using mouse primary CD25-CD4+ T cells with either DM (4 M) or vehicle in the presence or absence of stimulation by anti-CD3 and -CD28 antibodies.
Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T-cell activation and differentiation.
Specimen part, Treatment
View SamplesInvasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, KISS1 (kisspeptin), and its endogenous receptor, GPR54, has been reported in several cancers, but the significance of the KISS1/GPR54 axis in endometrial cancer metastasis has not been clarified. Metastin-10 is the minimal bioactive sequence of genetic products of KISS1. Clinicopathological analysis of 92 endometrial cancers revealed overall survival is improved in cancers with high expression of GPR54. Through RNAi and mousemodel analyses, metastin-10 was predicted to suppress invasion and metastasis of GPR54-expressing endometrial cancers. These data suggest that metastin-10 may induce genetic changes in the metastatic character of endometrial cancers.
GPR54 is a target for suppression of metastasis in endometrial cancer.
Specimen part, Cell line
View SamplesTo understand organ function it is important to have an inventory of the cell types present in the tissue and of the corresponding markers that identify them. This is a particularly challenging task for human tissues like the pancreas, since reliable markers are limited. Transcriptome-wide studies are typically done on pooled islets of Langerhans, which obscures contributions from rare cell types and/or potential subpopulations. To overcome this challenge, we developed an automated single-cell sequencing platform to sequence the transcriptome of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types. We identify cell type-specific transcription factors, a subpopulation of REG3A-positive acinar cells, and cell surface markers that allow sorting of live alpha and beta cells with high purity. This resource will be useful for developing a deeper understanding of pancreatic biology and pathophysiology of diabetes mellitus. Overall design: Islets of Langerhans were extracted from human cadaveric pancreata and kept in culture until single-cell dispersion and FACS sorting. Single-cell transcriptomics was performed on live cells from this mixture using an automated version of CEL-seq2 on live, FACS sorted cells. The StemID algorithm was used to identify clusters of cells corresponding to the major pancreatic cell types and to mine for novel cell type-specific genes as well as subpopulations within the known pancreatic cell types.
A Single-Cell Transcriptome Atlas of the Human Pancreas.
Specimen part, Subject
View SamplesUsing killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation
Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates.
No sample metadata fields
View SamplesContinuous regeneration of digestive enzyme (zymogen) secreting chief cells is a normal aspect of stomach function that is disrupted in pre-cancerous lesions. Regulation of zymogenic cell (ZC) differentiation is poorly understood. Here we profile Parietal, Pit, and Zymogenic cells for comparison and study.
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1.
Specimen part
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