Project description:Obesity-induced inflammation metabolic dysfunction, but the mechanisms remain elusive. Here we showed that the innate immune factor IRF3 is a direct transcriptional regulator of glucose homeostasis through induction of endogenous FAHFA hydrolase Aig1 in adipocytes. Adipocyte-specific knockout IRF3 protects mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.
Project description:Overnutrition leads to metabolic disorders such as obesity and diabetes. Enhanced inflammation has also been shown to be an essential player in the progression of metabolic diseases. However, how immune cells sense nutritional status and contribute to whole-body metabolism remain largely elusive. OGT-catalyzed protein O-GlcNAcylation is thought to be a metabolic sensor that modulates cell signaling. In this study, we show that overnutrition stimulates macrophage O-GlcNAc signaling. O-GlcNAc signaling suppresses macrophage proinflammatory activation and protects against diet-induced obesity and metabolic dysfunction. These findings thus identify macrophage O-GlcNAc signaling as a novel homeostatic regulator at the interface of inflammation and metabolism.
Project description:KDM4B (lysine demethylase 4B) in adipose tissues plays a critical role in energy balance, oxidation, lipolysis and thermogenesis. Loss of KDM4B in mice resulted in obesity associated with reduced energy expenditure and impaired adaptive thermogenesis. Mechanistically, we determined that KDM4B directly controls the expression of multiple metabolic genes.
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other