Project description:Transcriptome analysis comparing livers of 10 month old MANFHet mice and WT littermates revealed the induction of genes associated with inflammation, apoptosis, collagen deposition, usually observed in association with liver damage, along with alterations in lipid metabolism.
Project description:To investigate the effects of gene Fmod on affecting brain dysfunction and metabolic disorders by profiling the transcripome in the hypothalamus and liver of male Fmod_KO mice at 13 weeks old.
Project description:To investigate the effects of gene Bgn on affecting brain dysfunction and metabolic disorders by profiling the transcripome in the liver of male Bgn_KO and wild-type (WT, litter mate) mice at 13 weeks old.
Project description:Nonalcoholic fatty liver disease (NAFLD) is becoming a primary cause of liver damage in Western society. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD and may lead to liver cancer. Our previous long-term murine studies have shown the beneficial role of Aquamin, a red marine algae-derived (calcium, magnesium, additional trace elements-rich) supplement, in reducing liver injury and decreasing liver tumor incidence. The main objective of the study was to determine how manifestations and effects of NASH can be mitigated using Aquamin. We hypothesized that mice on a high-fat Western diet (HFWD) with minerals would exhibit less liver injury than mice on a HFWD without minerals. Methods: Two cohorts of MS-NASH mice (8-week-old) were placed on a HFWD with and without minerals for 16 weeks. An additional cohort of MS-NASH mice on the same HFWD was treated with obeticholic acid (OCA). C57BL/6 mice on a regular chow were included as a control. During the in-life phase of the study, weight changes were assessed weekly. At termination, livers were histologically assessed for steatosis and fibrosis by using hematoxylin and eosin, and picrosirius red staining. Liver tissue samples were also subjected to tandem mass tag (TMT) mass-spectroscopic proteomics for protein expression profile in individual mice. Results: Mice on HFWD gained more weight than mice on control diet, but there was no overall change in weight for mice on HFWD, irrespective of interventions. On histological assessment, there was no difference in steatosis between the two high-fat groups, but mice on Aquamin showed reduced picrosirius red staining or collagen deposition as compared to placebo on HFWD mice. Regarding proteomic profile, there was a clear distinction among control and HFWD groups. Placebo (on HFWD) mice were used for comparison. Aquamin intervention altered 91 proteins while OCA altered 84 proteins in liver samples with a 2-fold change. Of these, 57 proteins were common between Aquamin and OCA. Most of the proteins were upregulated. Aquamin upregulated 39 unique pathways (with a p-value <0.05) as assessed by the Reactome database. Some of the pathways significantly impacted by Aquamin were formation of cornified envelope; keratinization; gap junction assembly; type I hemidesmosome assembly; apoptosis-related; plasma lipoprotein assembly, remodeling and clearance; and hedgehog “off” state pathways. Proteins downregulated by OCA are mainly involved in the synthesis of bile acids and bile salts. Conclusion: The addition of dietary minerals may play a protective role in interfering with downstream advancement from steatosis to NASH. Our studies provide mechanistic insight into how mineral supplementation may contribute to the reduction in liver injury and tumor formation (one of the most devastating consequences) of fatty liver disease in the context of HFWD-induced steatosis.
Project description:Analyses of the vascular changes that occur following a chronic nitrate supplementation in old mice at a gene expression level and transcriptional profile have not been elucidated in depth. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of old and old nitrate treated mice, in which age-related vascular dysfunction was confirmed by endothelial dysfunction.
Project description:2-3 month old female C57Bl/6J mice were intravenously infected with 2x10^6 focus forming units of lymphocytic choriomeningitis virus strain Clone-13. Whole liver tissue was harvested in duplicated from uninfected control mice, uninfected 123d old mice, and from infected at 2, 8, 30, 60, and 123 days post infection. Three TMT 6-plex runs were carried out to monitor the changes in liver protein abundance during the entire course of infection. The first run included samples from day 2 and day 8 after infection along with the uninfected controls. Similarly, the second run included uninfected controls and samples from day 30 and day 60 after infection. The third run included samples day 123 after infection, the corresponding age matched control that was left uninfected for 123 days and the uninfected controls used in the other two runs. The uninfected controls were included in all the three runs as an internal control to monitor reproducibility between the runs.
Project description:Werner syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS is believed to be involved in different aspects of transcription, replication, and/or DNA repair. We generated a mouse model with a deletion in the helicase domain of the murine WRN homologue that recapitulates most of the WS phenotypes including an abnormal hyaluronic acid excretion, higher reactive oxygen species (ROS) levels, increased genomic instability and cancer incidence resulting in a 10-15% decreased life span expectancy. In addition, WS patients and Wrn mutant mice show hallmarks of a metabolic syndrome including premature visceral obesity, hypertriglyceridemia, insulin-resistant diabetes type 2 and associated cardiovascular diseases. In this study, we compared the expression profile of liver tissues from 3-month old Wrn mutant mice 3-month old to wild type animals before the mutant animals exhibited any microscopic phenotype.