Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1 and Spp1 in western diet-induced obesity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE133814 | GEO | 2019/07/04
REPOSITORIES: GEO
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Project description:BackgroundEnvironmental factors are critical in the development of age-related cognitive decline and dementia. A western diet (WD) can cause nutrient deficiency and inflammation that could impact cognition directly. It is increasingly recognized that innate immune responses by brain myeloid cells, such as resident microglia, and infiltrating peripheral monocytes/macrophages may represent an essential link between a WD, cognitive decline, and dementia. Our previous data demonstrated that chronic consumption of a WD induced inflammation through brain myeloid cells in aging mice and a mouse model of Alzheimer's disease (AD). However, the subtypes of myeloid cells that contribute to the WD-induced inflammation remain unclear.MethodsC57BL/6J (B6), myeloid cell reporter mice (B6.Ccr2RFP/+Cx3cr1GFP/+), and Ccr2-deficient mice (B6.Ccr2RFP/RFP) were fed a WD or a control chow diet (CD) from 2 to 6 or 12 months of age. CD11b+CD45lo and CD11b+CD45hi cells from WD- and CD-fed B6 or Ccr2-deficient mice were characterized using flow cytometry, RNA-sequencing, and immunofluorescence.ResultsCcr2::RFP expressing myeloid cells were significantly increased in brains of WD- compared to CD-fed mice, but were not elevated in Ccr2-deficient WD-fed mice. The percent of CD11b+CD45hi cells was significantly increased in WD- compared to CD-fed mice. Comparison of RNA-sequencing data with immune cell data in ImmGen supports that CD11b+CD45hi cells from WD-fed mice are enriched for peripheral monocytes and neutrophils. Ingenuity pathway analysis predicted these cells elicit proinflammatory responses that may be damaging to the brain. Using stringent criteria for gene expression levels between CD11b+CD45hi and CD11b+CD45lo cells, we identified approximately 70 genes that we predict are uniquely expressed in infiltrating cells, including Itgal, Trem1, and Spp1 (osteopontin, OPN). Finally, we show a significantly greater number of OPN+IBA1- cells in WD- compared to CD-fed mice that we propose are activated neutrophils based on ImmGen data. OPN+IBA1- cells are not significantly increased in Ccr2-deficient WD-fed mice.ConclusionsThese data further support the model that peripheral myeloid cells enter the brain in response to diet-induced obesity. Elucidating their contribution to age-related cognitive decline and age-related neurodegenerative diseases should offer new avenues for therapeutic intervention in Alzheimer's disease and related dementias, where diet/obesity are major risk factors.
| S-EPMC6700800 | biostudies-literature
Project description:Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1 and Spp1 in western diet-induced obesity
| PRJNA552580 | ENA
Project description:LV hypertrophy is associated with Western diet consumption, while intake of n-3 polyunsaturated fatty acids is associated with anti-hypertrophic effects. We treated rats for 12 weeks with either a Control diet, a Western diet or a Western + DHA diet. For each of the 3 dietary treatments there were 2 pooled samples of heart tissue (with each pooled sample representing 5 rats) for a total of 6 arrays. Microarray analysis identified 66 differentially expressed transcripts. Pathways were identified using Ingenuity and DAVID software. Array results from two pooled samples (5 rats in each pool) for n=10 per treatment group were used for comparisons. Comparisons between Western vs. Control, Western + DHA vs. Control and Western + DHA vs. Western diets was subjected to analysis to generate log fold changes. A dietary treatment of 12 weeks was used in an effort to produce LVH while limiting the development of comorbidities. Microarray analysis was performed on pooled samples, followed by qRT-PCR and Western blot analysis. Groups were Control, Western and Western + DHA. Comparisons between groups are expressed as LogFC (i.e. LogFC_WESvCTRL, LogFC_DHAVCTRL, LogFC_DHAvWES), available in Series supplementary files.
2013-11-22 | E-GEOD-52603 | biostudies-arrayexpress
Project description:LV hypertrophy is associated with Western diet consumption, while intake of n-3 polyunsaturated fatty acids is associated with anti-hypertrophic effects. We treated rats for 12 weeks with either a Control diet, a Western diet or a Western + DHA diet. For each of the 3 dietary treatments there were 2 pooled samples of heart tissue (with each pooled sample representing 5 rats) for a total of 6 arrays. Microarray analysis identified 66 differentially expressed transcripts. Pathways were identified using Ingenuity and DAVID software. Array results from two pooled samples (5 rats in each pool) for n=10 per treatment group were used for comparisons. Comparisons between Western vs. Control, Western + DHA vs. Control and Western + DHA vs. Western diets was subjected to analysis to generate log fold changes.
2013-11-22 | GSE52603 | GEO
Project description:The tongue is a heavily innervated and vascularized striated muscle that plays an important role in vocalization and swallowing. The surface of the tongue is lined with papillae which contain gustatory cells expressing various taste receptors. There is growing evidence to suggest our perceptions of taste and food preference are remodelled following chronic consumption of western diets rich in carbohydrate and fats. Our sensitivity to taste and also metabolism western diets may be a key factor in the rising prevalence of obesity but a systems-wide analysis is lacking. Here, we defined the proteomic landscape of the mouse tongue and quantified changes following chronic consumption of a chow or western diet for 7 months. We observed a dramatic remodelling of the tongue proteome including changes in fatty acid and mitochondrial metabolism. The expression of several receptors, and metabolic enzymes and hormones were also differentially regulated which is exciting as these may serve as novel therapeutic targets to potentially alter taste perception and food preference to combat obesity.
2021-09-10 | PXD025190 | Pride
Project description:To determine the effect of consumption of a quercetin-rich diet on obesity and dysregulated hepatic gene expression, C56BL/6J mice were fed for 20 weeks on control or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Chronic dietary intake of quercetin reduced body weight gain and visceral and liver fat accumulation, and improved hyperglyceamia, hyperinsulinaemia, dyslipidaemia in mice fed a Western-style diet. Feeding a Western-style diet altered expression of genes related to inflammatory responses, lipid metabolism and oxidative phosphorylation in C57BL/6J mice after 20 weeks. The results from exhaustive gene expression analysis showed that quercetin minimally influenced hepatic gene expression in mice fed the Western diet. The gene screening results (GSEA) were consistent with the notion that it did improve mitochondrial function to some extent. Quantitative RT-PCR analysis indicated that quercetin did influence important regulators of fat accumulation and metabolic disorders. Our results suggest that quercetin reduces fat accumulation presumably through decreasing oxidative stress and increasing PPARα expression, and the following improvement of gene expression related to steatosis in the liver. C56BL/6J mice were fed for 20 weeks on AIN93G (con) or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin for 20 weeks.
2012-05-29 | E-GEOD-38141 | biostudies-arrayexpress
Project description:SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (harlan, TD.88137) for 22 weeks, they were resistant to diet induced obesity and hepatic steatosis compared to WT controls. However, their hepatic insulin sensitivity was compromised when assessed with phospho-Akt levels after insulin injection. Therefore, we investigated hepatic gene expression using illumina beadchip array to explore mechanisms underneath the unique liver physiology in SHP-/- mice. Livers were collected from C57Bl/6 wild type and C57Bl/6 SHP-/- mice fed chow or western diet. The 1 microgram of total RNA obtained from individual mouse (n=4 per group) and subjected to illumina beadchip gene expression profiling.
2012-05-16 | E-GEOD-38013 | biostudies-arrayexpress
Project description:Western diet microbiome resilience Raw sequence reads
| PRJNA992061 | ENA
Project description:The study investigates the effect of a heterozygous MYBPC3 mutation combined with Western diet feeding on protein expression in a HCM mouse model. Hypertrophic cardiomyopathy (HCM) is the most common inherited genetic heart disease, characterized by asymmetric left ventricular hypertrophy and diastolic dysfunction. It is generally accepted that HCM is caused by mutations in genes encoding sarcomere proteins (e.g. MYBPC3, MYH7). However, not all mutation carriers will develop HCM and, moreover, phenotypical variation in terms of clinical presentation is large. The phenotypical expression of HCM thus requires additional disease modifiers on top of a sarcomere gene mutation. Clinical reports identify obesity and related comorbidities (diabetes, hyperlipidemia, hypertension) as a major factor contributing to disease expression and severity. We aimed to mimic this situation in a HCM mouse model by feeding a Western diet (8 weeks) to mice carrying a heterozygous mutation in MYBPC3. These heterozygous mice are phenotype negative under normal conditions, but developed cardiac dysfunction and hypertrophy upon Western diet feeding. The main goal of this proteomic screening is to identify clusters of proteins and pathways that are down/upregulated specifically in the left ventricle of mice suffering from a mutation and Western diet feeding. Also, we are interested in protein expression differences caused solely by mutation or Western diet. Group 1 are Wild type mice that received normal chow; group 2 are heterozygous mice that received normal chow; group 3 are Wild type mice that received a Western diet; group 4 are heterozygous mice that received a Western diet.
2023-10-01 | PXD043345 | Pride
Project description:SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (harlan, TD.88137) for 22 weeks, they were resistant to diet induced obesity and hepatic steatosis compared to WT controls. However, their hepatic insulin sensitivity was compromised when assessed with phospho-Akt levels after insulin injection. Therefore, we investigated hepatic gene expression using illumina beadchip array to explore mechanisms underneath the unique liver physiology in SHP-/- mice.
2012-05-17 | GSE38013 | GEO