Project description:Hepatic transcriptome of junctional adhesion molecule A knockout, F11r–/– mice fed a Western diet (WD) for eight weeks. A cohort of WD-fed mice were treated with IgG or α4β7 mAb for four weeks starting at week four following initiation of the WD.
Project description:Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD) relative to a heart-healthy diet (HHD) on microvessel transcriptomics and metabolomics of the brain temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were randomized to the WD or HHD starting at the age of 4 months and were fed the assigned diet for the following 6 months. The WD and HHD were isocaloric and had the same macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received a statin. Relative to HHD-fed pigs, WD-fed pigs had 2,172 genes differentially expressed (FDR<0.05) by diet, 796 upregulated and 1,376 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD, including cell energetics, neurotransmission, and inflammation resolution pathways. Enrichment in arginine, tyrosine, and lysine was observed in WD-fed pigs and enrichment in ergothioneine and S-adenosyl methionine in HHD-fed pigs. Statin treatment had very modest effects on brain vessel transcriptome. Our study suggests a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration.
Project description:To get further insights into the processes leading to attenuation of early stage atherosclerosis in the bortezomib treated LDLR-KO mice, microarray profiling of gene expression was performed on RNA taken from whole aortae of bortezomib treated LDLR-KO and sham- treated LDLR-KO mice fed a Western diet for 6 weeks and compared the changes in gene expression in both groups to non-atherosclerotic CD animals. Male 10-week-old LDLR-KO mice (B6.129S7-Ldlrtm1Her/J; JAX Mice, Boston) were fed a Western-type diet for 6 weeks ad libitum and received intraperitoneal injections of bortezomib (50 µg/kg body weight; WD+Bor) or saline (WD) twice weekly (n = 4). Mice that were fed normal diet served as chow diet control (CD; n = 4). Gene expression in aortic tissue was measured. Two independent experiments were performed.
Project description:The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of reproductive age adults consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father’s poor nutritional status has been shown to have negative consequences on fetal growth and development and ultimately impact the long-term adult health of the offspring. In this study we examined sperm and seminal plasma mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. Male mice were fed a diet to model either under (low protein diet (LPD)) or over (high fat/sugar (Western) diet (WD)) nutrition, LPD or WD supplemented with methyl-donors or a control diet before mating with age-matched control fed females. Male metabolic health was influenced by WD and MD-WD; with significant changes in serum lipids and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35). In vitro embryo development was revealed all sub-optimal diets with and without methyl-donors increased the rate of embryo development. As embryo development can be directed by sperm and seminal plasma mediated mechanism, we also examined the proteomic profile of the seminal plasma, revealing a significant number of changes in all groups compared to control (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19). Male diet also altered uterine gene expression examined via qPCR, specifically alterations in Cd14 and Ptgs1 were observed in response to male WD matings. Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive factors, which can ultimately alter embryonic development and the post-mating maternal environment. This study highlights potential direct (sperm mediated) and indirect (semen mediated) pathways in which a father's poor diet could shape the long-term health of his offspring.
Project description:To investigate the effect of Cyp2e1 and EtOH on mRNA expression in mouse tissues, we profiled total RNA expression using mouse tissues from Cyp2e1 -/- mice and Cyp2e1 +/+ mice upon EtOH fed mice compared to control. We compare the expression level of RNA and profile circular RNA expression using circular RNA junction.
Project description:miRNA expression was profiled before and during liver regeneration following 2/3 partial hepatectomy (PHx) in chronic ethanol-fed (EtOH) and pair-fed carbohydrate control (CHO) rats. Prior to PHx, EtOH animals were fed a liquid diet containing 36% of the calories from ethanol for 5 weeks. Left lateral and medial (LLM) lobes were removed at time of PHx and used as t = 0 biological controls. Remnant liver tissue (PHx) was harvested 1 h, 6 h, 12 h, and 24 h after PHx. RNA from 4 biological replicates was pooled for profiling miRNA expression on Agilent Rat miRNA Microarrays v1.0.
Project description:Accumulating studies support that the western diet (WD), a diet comprised of saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety, remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) is identified in the hypothalamus, a key brain area involved in both sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the role of the hypothalamic TAS1R3 in WD-induced anxiety using wild-type (WT) and Tas1r3 deficient (Tas1r3-/-) mice fed a normal diet (ND) or WD for 12 weeks. We evaluated anxiety levels with the open field test and the elevated plus maze test. Behavior tests showed WD increased anxiety in WT mice, whereas Tas1r3-/- mice were protected from WD-induced anxiety. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3-/- mice, we found 1,437 genes significantly regulated by Tas1r3 deficiency. In addition, bioinformatic analysis revealed that CREB-mediated maintenance of neuronal regeneration, which can prevent the development of anxiety, was enhanced in WD-fed Tas1r3-/- mice compared to WD-fed WT mice. In addition, in vitro studies further confirmed that Tas1r3 knockdown prevented suppression of CREB caused by high levels of glucose, fructose, and palmitic acid in adult hypothalamic neuronal cells. These results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of the WD on anxiety.
Project description:Poor parental health can influence the development and eventual health outcomes of their offspring. Many studies have detailed the maternal role yet a father’s health requires further examination as his poor nutritional status has also been shown to have negative consequences on fetal development and impact the long-term health of his offspring. The present study examined how preimplantation embryo development was altered by sub-optimal paternal diet, with specific focus on sperm- and seminal plasma-mediated mechanisms. To address this, male mice were fed a diet to model either under (low protein diet (LPD)) or over (high fat/sugar ‘Western’ diet (WD)) nutrition, LPD or WD supplemented with methyl-donors or a control diet (CD) before mating. Embryo development was assessed using in vitro time-lapse imaging of preimplantation embryos which revealed a significant increase in embryo development rates in all experimental groups when compared to CD embryos. Further analysis of the semen revealed a significant number of differentially expressed seminal plasma proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. This study highlights a role for paternal nutritional status influencing embryonic development and the maternal reproductive tract via changes to his metabolic and reproductive health. These findings demonstrate potential direct (sperm-mediated) and indirect (seminal plasma-mediated) pathways in which a father's poor diet could shape the long-term health of his offspring
Project description:To investigate whether taste receptor type 1 member 3 (TAS1R3) might serve as a key modulator of cognitive impairment led by WD-induced obesity, male Tas1r3-wild type (WT) and knockout (KO) mice were randomized to receive either a normal diet (ND) or western diet (WD) for 18 weeks. We performed gene expression profiling analysis using data obtained from RNA-seq of hippocampus of two WT mice fed a WD (WT-WD) and two KO-WD mice.