Project description:Prolonged exposure to a high-fat diet (HFD) exacerbates intestinal disease pathology, yet the early events preceding the development of gut inflammation remain poorly understood. Here we show that within 48 hours, HFD impairs intestinal group 3 innate lymphoid cells (ILC3) and their capacity to produce interleukin-22 (IL-22), critical for maintaining gut homeostasis. This loss of function was associated with rapid dysbiosis, increased gut permeability, and reduced production of antimicrobial peptides, mucus, and tight junction proteins. While saturated fatty acids metabolized through oxidation impaired ILC3 function, unsaturated fatty acids sustained IL-22 secretion by ILC3 through the formation of lipid droplets using DGAT enzymes. Upon inflammation, saturated fatty acids significantly impaired IL-22 production by ILC3 and increased the susceptibility of the gut to injury. Our findings reveal the differential acute impact of saturated and unsaturated fatty acids on gut homeostasis through distinct metabolic pathways in ILC3.
Project description:We used microarrays to unveil the gene expression alterations upon short-term HFD administration We found that short-term HFD administration impacts hepatic lipid biosynthesis and redox status
Project description:This SuperSeries is composed of the following subset Series: GSE38839: MicroRNA expression profiling after short-term exposure to TCDD in zebrafish embryos [agilent and exiqon array data] GSE39808: MicroRNA expression profiling after short-term exposure to TCDD in zebrafish embryos [miRNA-Seq data] Refer to individual Series
Project description:Using standardized, semipurified diets is a crucial factor for reproducibility of experimental nutritional studies. For the purpose of comparability and integration of research, two European consortia, Mitofood and BIOCLAIMS, proposed an AIN-93-based standard reference diet, the standardized BIOCLAIMS low-fat diet (LFD) as well as a high-fat diet (HFD). In order to evaluate the BIOCLAIMS LFD and HFD, we performed short-term (5 days) and long-term (12 weeks) feeding experiments using male C57BL/6 mice. The HFD has the same composition as the LFD except the fat content is increased to 40% energy in exchange for carbohydrates. Both diets were accepted by the animals and proof of principle was given that the BIOCLAIMS HFD increases body weight and body fat and affects glucose homeostasis. Short-term feeding trials (5 days) were performed in order to identify metabolic and molecular parameters which can serve as acute predictors for metabolic disorders due to high-fat diet-induced obesity. We analyzed gene expression in gonadal white adipose tissue of short- and long-term fed animals with whole genome microarrays. The BIOCLAIMS HFD strongly influenced gene expression in white adipose tissue after short- and long-term intervention. A total number of 973 and 4678 transcripts were significantly different between both diets after 5 days feeding and 12 weeks feeding, respectively. A total number of 764 transcripts encoding 549 genes were significantly differentially regulated between LF and HF animals after 12 weeks feeding as well as after 5 days feeding. Of these 549 overlapping genes, a substantial number (434 genes) were expressed at a lower level and 115 genes were expressed at a higher level in the HF mice compared to the LF mice. Without exception, all genes were regulated equally. Pathway analysis revealed a prominent role for genes involved in lipid metabolism, carbohydrate metabolism and oxidative phosphorylation. This was confirmed by quantitative real-time reverse transcription PCR. The high predictive value of gene expression changes in our short-term study compared to long-term high fat feeding is a promising step to get well-defined, early biomarkers that could shorten animal trials considerably and allow a more rapid and efficient screening of different compounds. C57BL/6J wildtype male mice, aged 12 weeks, received a low-fat diet or a high-fat diet for 5 days or 12 weeks. After sacrification, white adipose tissue depots were dissected, and immediately snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 4x44K microarrays.
Project description:Mycotoxin citrinin (CTN) is a secondary metabolite of fungi, becoming a contaminant widely found in foods, feeds, and fermented health supplements. CTN is known to disrupt microtubule and chromosome arrangement at high dose (50 - 150 μM), but the toxicological effect of CTN long-term exposure has not been clearly studied. To investigate the molecular mechanisms of genotoxic, clastogenic, and carcinogenic effects of CTN, RNA-seq was performed on HEK293 cells exposed to chronic 20 μM CTN treatment (3 days for short-term and 30 days for long-term). The transcriptomic profile may reveal some underlying mechanisms regarding chronic carcinogenic potential of CTN, providing information for risk assessment of CTN-contaminated grains and its commercial food products.
Project description:Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.
Project description:Using standardized, semipurified diets is a crucial factor for reproducibility of experimental nutritional studies. For the purpose of comparability and integration of research, two European consortia, Mitofood and BIOCLAIMS, proposed an AIN-93-based standard reference diet, the standardized BIOCLAIMS low-fat diet (LFD) as well as a high-fat diet (HFD). In order to evaluate the BIOCLAIMS LFD and HFD, we performed short-term (5 days) and long-term (12 weeks) feeding experiments using male C57BL/6 mice. The HFD has the same composition as the LFD except the fat content is increased to 40% energy in exchange for carbohydrates. Both diets were accepted by the animals and proof of principle was given that the BIOCLAIMS HFD increases body weight and body fat and affects glucose homeostasis. Short-term feeding trials (5 days) were performed in order to identify metabolic and molecular parameters which can serve as acute predictors for metabolic disorders due to high-fat diet-induced obesity. We analyzed gene expression in gonadal white adipose tissue of short- and long-term fed animals with whole genome microarrays. The BIOCLAIMS HFD strongly influenced gene expression in white adipose tissue after short- and long-term intervention. A total number of 973 and 4678 transcripts were significantly different between both diets after 5 days feeding and 12 weeks feeding, respectively. A total number of 764 transcripts encoding 549 genes were significantly differentially regulated between LF and HF animals after 12 weeks feeding as well as after 5 days feeding. Of these 549 overlapping genes, a substantial number (434 genes) were expressed at a lower level and 115 genes were expressed at a higher level in the HF mice compared to the LF mice. Without exception, all genes were regulated equally. Pathway analysis revealed a prominent role for genes involved in lipid metabolism, carbohydrate metabolism and oxidative phosphorylation. This was confirmed by quantitative real-time reverse transcription PCR. The high predictive value of gene expression changes in our short-term study compared to long-term high fat feeding is a promising step to get well-defined, early biomarkers that could shorten animal trials considerably and allow a more rapid and efficient screening of different compounds.