Beneficial Metabolic Effects of Rapamycin are Associated with Enhanced Regulatory Cells in Diet-Induced Obese Mice.
Ontology highlight
ABSTRACT: Analysis of rapamycin effects on white adipose tissue at gene expression level. The hypothesis tested in the present study was that rapamycin could modify immune cell composition and inflammatory state of the adipose tissue of obese mice. Total RNA prepared from the adipose tissue of obese mice treated with rapamycin or its excipient solution (referred as vehicle), compared to adipose tissue of lean mice.
Project description:Analysis of rapamycin effects on white adipose tissue at gene expression level. The hypothesis tested in the present study was that rapamycin could modify immune cell composition and inflammatory state of the adipose tissue of obese mice.
Project description:Rapamycin extends life span in mice, but it remains unclear if this compound also delays mammalian aging. Here, we present results from a comprehensive large-scale assessment of a wide rage of structural and functional aging phenotypes in mice. Rapamycin extended life span but showed few effects on a large number of systemic aging phenotypes, suggesting that rapamycin's effects on aging are largely limited to the regulation of age-related mortality and carcinogenesis. Total RNA obtained from 2-4 male mice of each analysed group (25 weeks old controls, 25 month old controls, 25 month old rapamycin treated)
Project description:Transcriptome analysis of white adipose tissue and bone (femur of the hind limbs) of the AEA001 mutant mouse. ENU generated mouse lines for osteoporosis. The mutation in the Ednra gene causes big ears and a flat short head. Due to a decreased body mass and a trend towards decreased glucose level white adipose tissue was analysed. Total RNA obtained from 4 male mutant mice was compared to 4 controls.
Project description:Gaining understanding of common complex diseases and their treatments are the main drivers for life sciences. As we show here, comprehensive protein set analyses offer new opportunities to decipher functional molecular networks of diseases and assess the efficacy and side-effects of treatments in vivo. Using mass spectrometry, we quantitatively detected several thousands of proteins and observed significant changes in protein pathways that were (dys-) regulated in diet-induced obesity mice. Analysis of the expression and post-translational modifications of proteins in various peripheral metabolic target tissues including adipose, heart, and liver tissue generated functional insights in the regulation of cell and tissue homeostasis during high-fat diet feeding and medication with two antidiabetic compounds. Protein set analyses singled out pathways for functional characterization, and indicated, for example, early-on potential cardiovascular complication of the diabetes drug rosiglitazone. In vivo protein set detection can provide new avenues for monitoring complex disease processes, and for evaluating preclinical drug candidates. Male C57BL/6 mice (age 6 wks) were fed for 12 weeks with high-fat diet (HFD) and than distributed into 3 groups. Mice were than fed over 3 weeks with HFD without compound ('HFD'), HFD with 4 mg/kg/d rosiglitazone ('HFD_RSG') or with 100 mg/kg/d amorfrutin 1 ('HFD_A1'). In parallel, mice were fed for 15 weeks with low-fat diet (LFD) as healthy control subjects. In addition, a group of mice was treated with 37 mg/kg/d amorfrutin 1 during the whole 15 weeks of HFD feeding ('HFD+A1prev'). Finally, visceral white adipose tissue (WAT) was harvested and RNA extracted. --> 2-4 biological replicates (2 mice per each replicate, RNA of 2 mice always pooled).
Project description:Gaining understanding of common complex diseases and their treatments are the main drivers for life sciences. As we show here, comprehensive protein set analyses offer new opportunities to decipher functional molecular networks of diseases and assess the efficacy and side-effects of treatments in vivo. Using mass spectrometry, we quantitatively detected several thousands of proteins and observed significant changes in protein pathways that were (dys-) regulated in diet-induced obesity mice. Analysis of the expression and post-translational modifications of proteins in various peripheral metabolic target tissues including adipose, heart, and liver tissue generated functional insights in the regulation of cell and tissue homeostasis during high-fat diet feeding and medication with two antidiabetic compounds. Protein set analyses singled out pathways for functional characterization, and indicated, for example, early-on potential cardiovascular complication of the diabetes drug rosiglitazone. In vivo protein set detection can provide new avenues for monitoring complex disease processes, and for evaluating preclinical drug candidates. Male C57BL/6 mice (age 6 wks) were fed for 12 weeks with high-fat diet (HFD) and than distributed into 3 groups. Mice were then fed over 3 weeks with HFD without compound ('HFD'), HFD with 4 mg/kg/d rosiglitazone ('HFD_RSG') or with 100 mg/kg/d amorfrutin 1 ('HFD_A1'). Finally, HEART tissue was harvested and RNA extracted. --> 3-4 biological replicates (2 mice per each replicate, RNA of 2 mice always pooled).
Project description:Gaining understanding of common complex diseases and their treatments are the main drivers for life sciences. As we show here, comprehensive protein set analyses offer new opportunities to decipher functional molecular networks of diseases and assess the efficacy and side-effects of treatments in vivo. Using mass spectrometry, we quantitatively detected several thousands of proteins and observed significant changes in protein pathways that were (dys-) regulated in diet-induced obesity mice. Analysis of the expression and post-translational modifications of proteins in various peripheral metabolic target tissues including adipose, heart, and liver tissue generated functional insights in the regulation of cell and tissue homeostasis during high-fat diet feeding and medication with two antidiabetic compounds. Protein set analyses singled out pathways for functional characterization, and indicated, for example, early-on potential cardiovascular complication of the diabetes drug rosiglitazone. In vivo protein set detection can provide new avenues for monitoring complex disease processes, and for evaluating preclinical drug candidates. Male C57BL/6 mice (age 6 wks) were fed for 12 weeks with high-fat diet (HFD) and than distributed into 3 groups. Mice were than fed over 3 weeks with HFD without compound ('HFD'), HFD with 4 mg/kg/d rosiglitazone ('HFD_RSG') or with 100 mg/kg/d amorfrutin 1 ('HFD_A1'). In parallel [GSE38854; Liver B], mice were fed for 15 weeks with low-fat diet (LFD) as healthy control subjects. In addition, a group of mice was treated with 37 mg/kg/d amorfrutin 1 during the whole 15 weeks of HFD feeding ('HFD+A1prev'). Finally, LIVER tissue was harvested and RNA extracted. --> 3-4 biological replicates (2 mice per each replicate, RNA of 2 mice always pooled). liver_HFD_*A and _*B samples are from the same biological source material, but the cRNA preparation and hybridization to Illumina arrays were performed at different days (i.e. technical repeats).
Project description:Gaining understanding of common complex diseases and their treatments are the main drivers for life sciences. As we show here, comprehensive protein set analyses offer new opportunities to decipher functional molecular networks of diseases and assess the efficacy and side-effects of treatments in vivo. Using mass spectrometry, we quantitatively detected several thousands of proteins and observed significant changes in protein pathways that were (dys-) regulated in diet-induced obesity mice. Analysis of the expression and post-translational modifications of proteins in various peripheral metabolic target tissues including adipose, heart, and liver tissue generated functional insights in the regulation of cell and tissue homeostasis during high-fat diet feeding and medication with two antidiabetic compounds. Protein set analyses singled out pathways for functional characterization, and indicated, for example, early-on potential cardiovascular complication of the diabetes drug rosiglitazone. In vivo protein set detection can provide new avenues for monitoring complex disease processes, and for evaluating preclinical drug candidates. Male C57BL/6 mice (age 6 wks) were fed for 12 weeks with high-fat diet (HFD) and than distributed into 3 groups. Mice were than fed over 3 weeks with HFD without compound ('HFD'), HFD with 4 mg/kg/d rosiglitazone ('HFD_RSG') or with 100 mg/kg/d amorfrutin 1 ('HFD_A1') [GSE38853; Liver A]. In parallel, mice were fed for 15 weeks with low-fat diet (LFD) as healthy control subjects. In addition, a group of mice was treated with 37 mg/kg/d amorfrutin 1 during the whole 15 weeks of HFD feeding ('HFD+A1prev'). Finally, LIVER tissue was harvested and RNA extracted. --> 3-4 biological replicates (2 mice per each replicate, RNA of 2 mice always pooled). liver_HFD_*A and _*B samples are from the same biological source material, but the cRNA preparation and hybridization to Illumina arrays were performed at different days (i.e. technical repeats).
Project description:We identify fibroblast growth factor 1 (FGF1) as a critical transducer in adipose tissue remodeling and link its regulation to peroxisome proliferator activated-receptor ? (PPAR?), the adipocyte master regulator and target of the thiazolidinedione (TZD) class of insulin sensitizing drugs. We show that FGF1 is highly induced in adipose tissue in response to high-fat diet (HFD) and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with HFD. Mechanistically, we show that transcription of FGF1 is directly regulated by an adipocyte-selective proximal PPAR response element, and that this PPAR?-FGF1 axis is evolutionarily conserved in mammals. This work describes the first phenotype of the FGF1 knockout mouse and establishes FGF1 as a new member of the NR-FGF axis critical for maintaining metabolic homeostasis and insulin sensitization. Total RNA was obtained from epidydimal white adipose tissue (eWAT) and livers from 6 month old wild-type and FGF1-/- mice after 16 weeks on normal chow or high-fat diets.
Project description:When food was removed for 6 hours, 43 genes, including Angptl4, changed their expression more than two-fold. Food was removed from young rats at 07:30. Six hours later, samples of epididymal adipose tissue was taken for analysis.
Project description:Our hypothesis is that in IBD patients intestinal bacteria translocation into the intra-abdominal fat depots affects adipocyte morphology and gene expression. The study aimed to study adipocyte gene expression of omental (OM) and mesenteric (MES) adipose tissue of ulcerative colitis (UC) and crohn's disease (CD). Total RNA was extracted from isolated adipocytes from omental and mesenteric adipose tissue of CD and UC patients. Microarray experiments were performed in duplicates of 4 different pools of RNAs extracted from adipocytes isolated from OM and MES of UC patients (n=5) and CD patients (n=5) respectively.