Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes, in bone marrow cells (BMC) and spleen (SPL). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison. Following 8 weeks on low fat diet (LFD), high fat diet (HFD) rich in saturated fatty acids (HFD-S), or HFD rich in PUFA (HFD-P), tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT) were mainly affected by HFD per se (both HFD-S and HFD-P). In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. Remarkably, the spleen, showed a major response to HFD-P, but not to HFD-S, whereas the LIV exhibited different responses to both of the HFDs. Further, HFD-P corrected the metabolic phenotype induced by HFD-S. Hence, the quantity and composition of dietary fatty acids affected the transcriptome in a distinct manner. Especially, PUFA prompted a specific regulation of immune related genes in the spleen. Thus, PUFA can regulate immune function by influencing gene expression.
Six Tissue Transcriptomics Reveals Specific Immune Suppression in Spleen by Dietary Polyunsaturated Fatty Acids.
Sex, Specimen part
View SamplesCharacterize the transcriptional response to INO2 and INO4 expression level (INO-level) and efficient factor
Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level (INO2 and INO4) on lipid metabolism in yeast.
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View SamplesTo investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and transcriptome in mice.
Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice.
Sex, Specimen part, Time
View SamplesAlzheimers disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid- peptides (A) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of A associated with AD are A40 and A42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind A toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either A40 or A42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of A42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in A42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that A42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of A40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of A toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-β (Aβ) Toxicity in Yeast.
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View SamplesIn this study we focus on two Saccharomyces cerevisiae strains with varying production of heterologous -amylase and we compare the metabolic fluxes and transcriptional regulation at aerobic and anaerobic conditions, in particular with the objective to identify the final electron acceptor for protein folding.
Anaerobic α-amylase production and secretion with fumarate as the final electron acceptor in Saccharomyces cerevisiae.
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View SamplesThe protein secretory pathway must maintain homoeostasis while producing a wide assortment of proteins in different conditions. It is also used extensively to produce many useful proteins in biotechnology. As such, secretory pathway dysfunction can be highly detrimental to the cell, resulting in the molecular basis for many human diseases, and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging.
Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress.
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View SamplesIn this study we focus on two Saccharomyces cerevisiae (CEN. PK series) strains producing either insulin precursor or amylase and we compare the transcriptional regulation at different dilution rates, in particular with the objective to identify the relationship between cell metabolism and recombinant protein production.
Correlation of cell growth and heterologous protein production by Saccharomyces cerevisiae.
Treatment
View SamplesFatty acid synthesis is closely linked to nutrient availability and cellular energetic status. The committed step in fatty acid synthesis is the acetyl CoA carboxylase. Eukaryotes have two genes encoding acetyl CoA carboxylases, one encoding a cytosolic enzyme and another coding for a mitochondrial enzyme. They catalyze the synthesis of malonyl CoA in the cytosol and the mitochondria, respectively. While cytosolic malonyl CoA is the precursor for fatty acid synthesis, mitochondrial malonyl CoA controls the transfer of fatty acyl group into the mitochondria by inhibiting carnitine/palmitoyl transferase activity and thus, regulates -oxidation. In Saccharomyces cerevisiae, -oxidation is restricted to the peroxisomes, raising the question of the function of the mitochondrial isoform (HFA1). In this study, we replaced the cytosolic Acc1 with Hfa1 expressed in the cytosol by removing the mitochondrial leader peptide, under control of the HFA1 promoter. We studied fatty acid synthesis and transcription profiles in this strain during starvation for carbon or nitrogen, using glucose or ethanol as the carbon source. Under all the conditions studied, the key sensor of energetic status, Snf1, was activated, indicating active inhibition of fatty acid synthesis. The pool size of fatty acids was smaller when Acc1 was replaced with truncated Hfa1 for fatty acid synthesis. Yet, the transcription profiles were similar in both the cases. These results point towards the conclusion that Hfa1 is either catalytically less efficient or it is more sensitive to inhibition by Snf1.
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Treatment
View SamplesMicroorganisms are exposed to large variations in nutrient availability in nature. To cope with these variations and sustain growth, they maximize the utility of the available nutrients and adapt to nutritional deficiencies. We studied the transcriptional and metabolic dynamics in Saccharomyces cerevisiae in response to a gradual transition from glucose-limited growth to ammonia-limited growth under aerobic or anaerobic conditions.
No associated publication
Time
View SamplesReconstructed mutants of yeast by inverse metabolic engineering were characterized by fermentation physiology and tools from systems biology.
Recovery of phenotypes obtained by adaptive evolution through inverse metabolic engineering.
Time
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