ABSTRACT: Peripheral blood mononuclear cells gene expression reflects adaptive response and metabolic damage associated to the intake of diets with an unbalanced proportion of macronutrients
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.
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.
Project description:Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy men ingested saturated (SFA) or poly unsaturated (PUFA) fat-rich diets for six weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with PUFA. In mice, eucaloric feeding of human PUFA and SFA diets lowered hepatic triacylglycerol content compared to low-fat fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.
Project description:in vivo microarray study of transcriptional changes in porcine peripheral blood mononuclear cells (PBMCs) due to dietary intake of phosphor
Project description:in vivo microarray study of transcriptional changes in porcine peripheral blood mononuclear cells (PBMCs) due to variable dietary intake of calcium and phosphorus
Project description:Adequate intake of protein among older adults is associated with better health outcomes, but conflicting results makes it difficult to define the optimal intake. To further understand the impact of protein intake on metabolic processes we studied genome-wide gene expression changes in peripheral blood mononuclear cells (PBMCs) in home-dwelling old subjects after increased protein intake for 12 weeks.
Project description:In the end-stage of MM (PD9), malignant PCs appeared in the patient's peripheral blood (PB), the proportion of which reached 10%. Her PB mononuclear cells (PBMC) were used for scRNA-seq.
2021-12-03 | GSE188632 | GEO
Project description:The response of gut microbiota to unbalanced diets
Project description:During kidney transplantation, ischemia reperfusion injury (IRI) is inevitable and leads to oxidative stress and inflammation. We investigated the role of macronutrients in the effects of dietary restriction on both a phenotypical and transcriptional level, thereby comparing protective and nonprotective diets in search for pathways and regulators involved in the protection against IRI.
Project description:This study aimed to explore the molecular basis of peripheral immune cells and the features of adaptive immune repertoire at a single cell level. We profiled 36,849 peripheral blood mononuclear cells from AD patients with amyloid-positive status and normal controls with amyloid-negative status by 5' single-cell transcriptome and immune repertoire sequencing using the cell ranger standard analysis procedure. We revealed five immune cell subsets, CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes-macrophages cells, and disentangled the characteristic alterations of cell subset proportion and gene expression patterns in AD. Thirty-one cell type-specific key genes, comprising abundant human leukocyte antigen genes, and multiple immune-related pathways were identified by protein-protein interaction network and pathway enrichment analysis. We also found high-frequency amplification clonotypes in T cells and B cells and decreased diversity in T cells in AD. As clone amplification suggested the activation of an adaptive immune response against specific antigens, we speculated that the peripheral adaptive immune response, especially mediated by T cells, may have a role in the pathogenesis of AD. This finding may also contribute to further research regarding disease mechanism and the development of immune-related biomarkers or therapy.
