Project description:Gene expression profiles in the liver of 9-week-old wild type and diabetic db/db mice were measured by high-throughput sequencing to detect the differentially expressed genes Gene expression profiles of 9-week-old wild type and diabetic db/db mice were generated by high-throughput sequencing using Illumina Genome Analyzer
Project description:Assembly of HSPGs in the liver is defective in diabetes mellitus. A major consequence is impaired clearance of post-prandial lipoproteins, which ordinarily depends on the binding of these particles to hepatic HSPGs. Impaired clearance leads to prolonged exposure of the arterial wall to these harmful lipoproteins. We pin-pointed suppression of NDST-1 in livers of type 1 diabetic rats as at least a partial explanation for defective HSPG assembly. Dr. Williams' lab examined glycan-related gene expression in the livers of three groups of mice: wild-type, ad-lib-fed type 2 diabetic mice (db/db), and calorically restricted db/db mice (caloric restriction was shown several years ago to correct their clearance of atherogenic post-prandial lipoproteins). The results will indicate the molecular basis for defective HSPG assembly in type 2 diabetes, which is a question of considerable medical importance. RNA preparations from mice livers (wild-type, ad-lib-fed type 2 diabetic mice, and calorically restricted mice) were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.
Project description:Small RNA profiles in the liver of 9-week old wild type and diabetic db/db mice were measured to detect the differentially expressed small RNAs. Small RNA profiles of 9-week old wild type (WT) and diabetic db/db mice were generated by deep sequencing using Illumina Genome Analyzer.
Project description:We reported a 28-day Intermittent fasting (IF) regimen improved cognitive deficits in db/db mice via a microbiota-metabolites-brain axis assessed by behavioral tests and multiple-omics analysis (transciptomics, 16S rRNA sequencing and metabolomics). Here we present transcriptomics data of mice hippocampus. A total of 310.85Gb clean RNA-SEQ reads of all mice with an average depth of 3.86x were obtained and were then mapped against the Mus musculus genome to obtain the gene expression FPKM values for each sample. We detected 27,094 genes (including 1,345 new predicted genes with no annotation) with FPKM value. Among them, 1,181 genes were found to be only highly expressed in db/db-IF mice compared to db/db and db/m mice, using Differentially Expressed Genes (DEG) analysis, most of which enriched in mitochondrial-related GO terms. Besides, IF strongly elevated genes related to KEGG pathway of oxidative phosphorylation (OXPHOS) via up-regulating mitochondrial located genes expression. In consistent with results from RNA-sequencing analysis, the qPCR analysis confirmed that mitochondrial and metabolic genes expressed were upregulated by IF in db/db mice. In conclusion, IF regimen significantly enhanced mitochondrial and energy metabolism related genes expressions in diabetic mice hippocampus.
Project description:In this study, we discovered cytosolic and mitochondrial fragments resulting from tRNA and mt-tRNA cleavage, which may act as new regulators of cellular and metabolic functions. We analyzed hundreds of these fragments in the pancreatic islets of db/db mice and compared them to heterozygous control db/+ mice. At 16 weeks of age, db/db mice exhibit obesity, insulin resistance, and glucose intolerance. In our analysis, we identified 3858 tRFs in the islets of db/db mice, among which 342 exhibited significant changes (≥ 2 fold; adjusted p value ≤ 0.05) compared to controls. Of these, 199 tRFs showed increased levels, while 170 tRFs showed decreased levels in the pre-diabetic mice. Notably, a striking majority (147 out of 170) of the tRFs with reduced abundance in the islets of db/db mice were derived from the cleavage of tRNAs encoded by the mitochondrial genome. Our findings reveal a significant reshaping of mitochondrial tRFs in pre-diabetic conditions, coinciding with a well-established mitochondrial metabolic defect under these conditions. Specifically, we demonstrated that a fragment (named mt-tRF-LeuTAA) resulting from the cleavage of mt-tRNA-LeuTAA, encoded by the mitochondrial genome and found to be reduced in the islets of db/db mice, acts as a key regulator of mitochondrial OXPHOS functions, mitochondrial membrane potential, the insulin secretory capacity of ß-cells, and the insulin sensitivity of myotube muscle cells.