Project description:Diet-induced obesity (DIO) is associated with a decreased oral fat detection in rodents. This blunted gustatory detection has been explained by an impairment of the lipid-mediated signaling in taste bud cells (TBC). However, factors responsible for this defect remain elusive. To better understand the mechanisms involved, circumvallate papillae from Lean, DIO and former DIO mice were analyzed with a transcriptomic approach. [using Agilent Sureprint G3 Mouse microarrays (8x60K, design 028005)]
Project description:Gene expression profiling by microarray analysis of tumors formed from inoculation of the established human breast cancer cell line MDA-MB-468 in two groups of mice: lean control and DIO mice.
Project description:Given that celastrol?s leptin-sensitizing effect requires high levels of circulating leptin, but lean mice have low levels of circulating leptin so that celastrol has no effect on lean mice. Analysis celastrol-induced hypothalamic gene expression profile change in lean mice will also be serving as negative control for DIO mice analysis.
Project description:Introduction: Obestatin is a controversial gastrointestinal peptide purported to have metabolic actions. Objectives: This study investigated whether treatment with a stable obestatin analogue (PEG-OB(Cys10, Cys13) changed plasma metabolite levels firstly in lean and subsequently in diet-induced obesity (DIO) C57BL6/J mice. Method: Untargeted LC-HRMS metabolomics experiments were carried out in ESI+ mode with plasma extracts from both groups of animals. Data were normalised, multivariate and univariate statistical analysis performed and metabolites of interest putatively identified. Result: In lean mice, 39 metabolites were significantly changed by obestatin treatment and the majority of these were increased, including various C16 and C18 moieties of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and monoacylglycerol, along with vitamin A, vitamin D3, tyrosine, acetylcarnitine and 2alpha-(hydroxymethyl)-5alpha-androstane-3beta,17beta-diol. Decreased concentrations of glycolithocholic acid, 3-dehydroteasterone and various phospholipids were observed. In DIO mice, 25 metabolites were significantly affected and strikingly, the magnitudes of changes here were generally much greater in DIO mice than in lean mice, and in contrast, the majority of metabolite changes were decreases. Four metabolites affected in both groups included glycolithocholic acid, and three different long-chain (C18) phospholipid molecules (phosphatidylethanolamine, platelet activating factor (PAF), and monoacylglycerol). Metabolites exclusively affected in DIO mice included various phosphatidylcholines, lysophosphatidylcholines and fatty acyls, as well as creatine and oxidised glutathione. Conclusion: This investigation demonstrates that obestatin treatment affects phospholipid turnover and influences lipid homeostasis, whilst providing convincing evidence that obestatin may be acting to ameliorate diet-induced impairments in lipid metabolism, and it may influence steroid, bile acid, PAF and glutathione metabolism.
Project description:We compared gene expression pattern of hepatocytes isolated from lean and diet-induced obesity (DIO) mice. Genes increased >2-fold in DIO mice were further filtered based on >2-fold change between hepatic gene expression from DIO mice treated with anti-VLA-4 and those with IgG