Dataset Information

The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes.

ABSTRACT: Obesogens are chemicals that predispose exposed individuals to weight gain and obesity by increasing the number of fat cells, storage of fats into existing cells, altering metabolic rates, or disturbing the regulation of appetite and satiety. Tributyltin exposure causes differentiation of multipotent stromal stem cells (MSCs) into adipocytes; prenatal TBT exposure leads to epigenetic changes in the stem cell compartment that favor the production of adipocytes at the expense of bone, in vivo. While it is known that TBT acts through peroxisome proliferator activated receptor gamma to induce adipogenesis in MSCs, the data in 3T3-L1 preadipocytes are controversial. Here we show that TBT can activate the RXR-PPAR? heterodimer even in the presence of the PPAR? antagonist GW9662. We found that GW9662 has a 10-fold shorter half-life in cell culture than do PPAR? activators such as rosiglitazone (ROSI), accounting for previous observations that GW9662 did not inhibit TBT-mediated adipogenesis. When the culture conditions are adjusted to compensate for the short half-life of GW9662, we found that TBT induces adipogenesis, triglyceride storage and the expression of adipogenic marker genes in 3T3-L1 cells in a PPAR?-dependent manner. Our results are broadly applicable to the study of obesogen action and indicate that ligand stability is an important consideration in the design and interpretation of adipogenesis assays.

SUBMITTER: Li X

PROVIDER: S-EPMC3281769 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes.

Li Xia X Ycaza John J Blumberg Bruce B

The Journal of steroid biochemistry and molecular biology 20110321 1-2

Obesogens are chemicals that predispose exposed individuals to weight gain and obesity by increasing the number of fat cells, storage of fats into existing cells, altering metabolic rates, or disturbing the regulation of appetite and satiety. Tributyltin exposure causes differentiation of multipotent stromal stem cells (MSCs) into adipocytes; prenatal TBT exposure leads to epigenetic changes in the stem cell compartment that favor the production of adipocytes at the expense of bone, in vivo. Whi ...[more]

PMID: 21397693

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Project description:Obesogenic compounds are chemicals that might have an influence on obesity development through in utero or chronic lifetime exposure. Tributyltin (TBT) is one of the most studied obesogenic compounds, inducing adipogenesis in vitro and increasing body fat after in utero exposure of mice. This study was designed to unravel the molecular mechanisms of TBT, using microarray analysis, and to evaluate the use of toxicogenomics for obesogen screening. The murine 3T3-L1 cell line was used to study TBT induced adipogenesis. Lipid staining as well as gene expression measurements of an adipocyte specific marker gene were performed to select relevant concentrations (10 nM, 50 nM) and time points (day1, day10) for microarray analysis. Additionally, solvent control and positive control (MDI) treated 3T3-L1 cells were included in the analysis. The microarray results were analysed using GO enrichment and Pathway analysis tools, which revealed enrichment of several GO terms involved in energy and fat metabolism after 10 days of TBT exposure. Pathway analysis unveiled PPAR signalling pathway as the sole pathway significantly enriched after 1 day and the most significantly enriched pathway after 10 days of exposure. By examination of effects on both cell physiological and gene expression level we provide a detailed overview of TBT induced obesogenic mechanisms. To our knowledge, this is the first study delivering an in depth mechanistic outline of the mode of action of TBT as an obesogen. Furthermore, our results show that combining omics with 3T3-L1 cells is promising for screening of potential obesogenic compounds. A separate v+2 A-optimal hybridization design was used for each time-point. Using this design each exposure condition is represented by three biological replicates, with each biological replicate analysed in technical duplicate while applying the dye swap principle to correct for dye bias. Two concentrations of TBT (10 nM, 50 nM), DMSO and MDI (positive control, adipogenic hormone cocktail) were the conditions tested, at two time-points (day 1 and day10).

Dataset Information

The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes.

Publications

The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes.

Similar Datasets

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