ABSTRACT: Leptin deficient mice is an appealing model for studying of metabolic syndromes. In this data, we provide 7 different tissues’ RNA-seq reads for each leptin-deficient mice (ob/ob) and wild type mice.
Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison Leptin deficient (ob/ob) mice were continuously administered leptin over 12-days using central (intracerebroventricular) or peripheral (subcutaneous) route of administration. Liver RNA was extracted and hybridized to Illumina microarrays and gene expression data was analyzed. The global gene expression profiles were compared after the central and peripheral leptin treatments in ob/ob mice and C57BL6 mice were used for the baseline gene expression.
Project description:Ob/ob mice were given 0, 12.5 or 25 ng/hr leptin through an osmotic pump. After 12 days, livers RNA was prepared and illumina microarrays were done. We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma [glucose] and [insulin]. We found that a leptin dose of 12.5 ng/hour significantly lowers blood glucose and that 25 ng/hour of leptin normalizes plasma glucose and insulin without significantly reducing body weight, thus establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 as being regulated by leptin with a similarly high potency. Over-expression of IGFBP2 by an adenovirus reversed diabetes in insulin resistant ob/ob, Ay/a and diet-induced obese mice (DIO), as well as insulin deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a three-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment in ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.
Project description:We hypothesize that gene expression in the lungs of these differentially-treated mice are divergent thus contributing to the disparity in their phenotypes. More specifically, (1) Effects of Leptin-treatment of ob/ob postnatal mice lungs are known to be volume-dependent from 2 to 10 wks of age, and are independent of the hypometabolism associated with leptin deficiency. ; (2) Leptin is critical to postnatal lung remodeling, particularly related to enlarged alveolar surface area. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between lungs of leptin or saline-treated ob/ob postnatal mice. Keywords: leptin, ob, lung
Project description:Ob/ob mice are characterized by a defect in leptin synthesis. In this study, the contribution of leptin deficiency to the deregulation of miRNA expression in ob/ob mice was determined by comparing leptin infused ob/ob mice to saline control.
Project description:We hypothesize that gene expression in the lungs of these differentially-treated mice are divergent thus contributing to the disparity in their phenotypes. More specifically, (1) Effects of Leptin-treatment of ob/ob postnatal mice lungs are known to be volume-dependent from 2 to 10 wks of age, and are independent of the hypometabolism associated with leptin deficiency. ; (2) Leptin is critical to postnatal lung remodeling, particularly related to enlarged alveolar surface area. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between lungs of leptin or saline-treated ob/ob postnatal mice. Experiment Overall Design: This study utilizes microarray analysis to test these hypotheses. Three sets of lungs were harvested from both treatments (Leptin or Saline) at around 1 mo. postnatal. RNA was isolated and used for global gene expression profiling (Affymetrix Mouse 430A array). Statistically significant gene expression was determined as a minimum 6 counts of 9 pairwise comparisons, minimum 1.5-fold change, and p < 0.05.
Project description:Lean or obese C57BL/6JHamSlc-ob/ob (ob/ob) were developed continuous leptin (or vehicle) treatment for 6 weeks. Lung samples were generated from male mice of lean or obese ob/ob on 3 days post infection of mouse-adapted SARS-CoV-2.
Project description:Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis of type 2 diabetes, may be a cause or consequence of altered protein expressions profiles. Proteomics technology offers enormous promise to investigate molecular mechanisms underlying pathologies, however, the analysis of skeletal muscle is challenging. Using a state-of-the-art mass spectrometry (MS) based workflow, we performed a global proteomics analysis of skeletal muscle from leptin-deficient, obese, type 2 diabetic (ob/ob) and lean mice, identifying more than 6,000 proteins with 118 proteins differentially regulated in obesity. This included protein kinases, phosphatases, and secreted and fiber type associated proteins. Enzymes involved in lipid metabolism in skeletal muscle from ob/ob mice were increased, providing evidence against reduced fatty acid oxidation in lipid-induced insulin resistance. Mitochondrial and peroxisomal proteins, as well as components of pyruvate and lactate metabolism were likewise increased. Finally, the skeletal muscle proteome from ob/ob mice displayed a shift towards the ‘slow fiber type’. This detailed characterization of obese rodent models of type 2 diabetes demonstrates an efficient workflow for skeletal muscle proteomics, which may easily be adapted to other complex tissues.
Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison
Project description:Bariatric surgical techniques are known to cause weight loss and diabetes remission to varying degrees in severly obese patients. However, the mechanisms involved in the restoration of beta-cell function remain to be uncovered. In this study, the leptin-deficient ob/ob mouse was used as a model to investigate the effect of EGA bariactric surgery on pancreatic islet gene expression.
Project description:Bariatric surgical techniques are known to cause weight loss and diabetes remission to varying degrees in severly obese patients. However, the mechanisms involved in the restoration of beta-cell function remain to be uncovered. In this study, the leptin-deficient ob/ob mouse was used as a model to investigate the effect of EGA bariactric surgery on pancreatic islet miRNA expression.