Project description:Tissue inflammation is a key factor underlying insulin resistance in established obesity. Several models of immuno-compromised mice are protected from obesity-induced insulin resistance. However, it is unanswered whether inflammation triggers systemic insulin resistance or vice versa in obesity. The purpose of this study was to assess these questions. 8-week-old C57BL/6J male mice was treated with 60% HFD for 0 day (NCD), 3 days, and 7 days. Eipididymal fat was fractionated. Each groups have three replicates.
Project description:How autoimmunity is initiated in Multiple Sclerosis (MS) is unknown, but both genetic and environmental factors have been implicated. Female physiology is associated with a three times higher risk of MS and the ratio of woman to men diagnosed with MS has been increasing over time, suggesting that environmental factors are interacting with female sex to initiate this disease. One MS risk factor that has been increasing that interacts with female sex is obesity. Being overweight or obese as an adolescent increases one’s risk of MS by 2-fold and this risk increases if one is female. To explore how obesity and female sex interact to control T helper autoimmunity, we conducted a proteomic screen on the serum of male and female healthy weight and obese participants that were affected or not affected by MS. We found that obese individuals, regardless of disease status, exhibited a prominent upregulation of proteins in pathways associated with the damage-associated S100 protein pathway, T helper 1 (Th1), IL-17 pathways and RIG-I/Interferon pathways and that this increase was more prominent in women. To explore the mechanisms of how female sex interacts with increased adiposity to regulate CNS autoimmunity, we modeled a diet-induced overweight (DIO) state in mice by placing animals on high fat diet for 4 weeks and then inducing experimental autoimmune encephalomyelitis (EAE), a model of MS. We found that DIO enhanced EAE severity in mice of both sexes compared to controls and this effect was more pronounced in female mice. The increased severity in the female DIO mice associated with a greater accumulation of pathogenic IFN-+IL-17+ CD4+ cells in the CNS and more severe tissue damage. Further studies of mice at steady-state revealed that DIO increased the frequency of CD44hiCD4+ T cells and enhanced the potential of naïve CD4+ T cells to produce IFN-This phenotype of higher T cell IFN-was also observed in female humans who were overweight. Furthermore, IFN-α was detected at significantly increased levels in the serum of the DIO-female compared to DIO-male or sex-matched control mice. Loss of IFN-α receptor in T cells negated the increases in Th1 inflammation and EAE severity caused by DIO in female mice. These results highlight that an overweight state may interact with female sex to selectively enhance Th1 responses and CNS autoimmunity by increasing type I and type I IFN signalling in T cells.
Project description:Our research is helpful to understand the physiological and pathological level changes caused on the macrophages of islet in HFD conditional, to find the different mechanism or signaling pathway compared with NCD
Project description:C57BL/6 male mice were fed a standardized NCD or HFD after weaning (4 weeks of age) over a course of 12 weeks. Normal chow diet (NCD) fed animals served as Controls
Project description:C57BL/6 male mice were fed a standardized NCD or HFD after weaning (4 weeks of age) over a course of 12 weeks. Normal chow diet (NCD) fed animals served as Controls Biotin-labeled cDNA was synthesized using GeneChip Whole Transcript Sense Labeling Assay (Affymetrix) according to vendor’s instructions. After fragmentation, cDNAs were hybridized for 17h at 45°C on Affymetrix Mouse Gene 1.0 ST Arrays. The Arrays were washed and stained in the GeneChip Fluidics Station 450 and scanned on a GeneChip Scanner 3000 7G (Affymetrix). Data intensities were log transformed and normalized with a quantile normalization method using Affymetrix Power Tools. Differentially expressed genes were identified according to statistical evidence indicated by Student's t-test and fold change statistics
Project description:To identify novel neurocircuits activated upon short-term HFD feeding, we employed phosphoribotrap-profiling, which allows for the unbiased identification of alterations in neuronal activation via immunoprecipitation of phosphorylated S6 ribosomal protein-tagged ribosomes from hypothalamic extracts of mice exposed to either 3 days of normal chow diet or HFD-feeding. We have analyzed mRNA selectively expressed in hypothalamic cells activated by a either normal chow diet (NCD)-feeding for 3 days or high fat diet (HFD)-feeding for 3 days. 10-week-old male C57/BL6N mice were put either on a normal chow diet or a high fat diet for 3 days. Afterwards, mice were sacrificed by cervical dislocation. The hypothalamus was rapidly dissected using a stainless steel brain matrix and immediately frozen in liquid nitrogen. Hypothalamic tissues were pooled (8 per IP).
Project description:To understand the fibrotic response in the CDA-HFD induced NASH fibrosis model, we performed RNA-seq on liver samples collected from mice fed with normal chow (week 0) or CDA-HFD chow (weeks 8 and 16).