The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARgamma). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARgamma activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARgamma antagonists, suggesting that activation of PPARgamma mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARgamma target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time.

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South polar firn cores spanning the last millennium have been analyzed to determine the nitrate background level of high‐latitude precipitation and its temporal variations. The resulting data reveal no evidence of a positive correlation between solar activity (11‐year solar cycle, low solar activity time periods, and solar proton events) and the NO3 content of south polar snow. These data therefore suggest that NOx production in the upper stratosphere, mesosphere, and thermosphere does not contribute significantly to the antarctic NO3 budget. This study of the NO3 content of high latitude precipitation suggests a major contribution by lightning (from a third to a half of the total) and by NOx produced in the lower stratosphere (approximately a third from N2O oxidation and to a lesser extent galactic cosmic rays) to the NO3 budget of this background atmosphere, the remaining portion being related to the present NOx surface sources of the southern hemisphere. For the first time, our data point to a decrease of NO3 content when very large amounts of sulfuric acid are present in South Pole snow layers. This observation suggests a possible interaction (via the hydroxyl radical) between S‐ and N‐derived species when large quantities of SO2 are injected by volcanic eruptions. Although the deposition mechanism of HNO3 in South Pole snow layers is far from well understood, our data suggest that only a minor amount of this compound is deposited directly on surface snow layers. Finally, the role played by particles (volcanic ash, terrestrial impurities, or ice particles) to enhance the uptake of odd nitrogen from the atmosphere by heteregeneous processes is discussed. In particular, it is suggested that in late winter, under certain meteorological conditions leading to ice particle formation, a significant uptake of HNO3 from the lower stratosphere can occur.

Background: Bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE), used in manufacturing coatings and resins, leach from packaging materials into food. Numerous studies suggested that BPA and BADGE may have adverse effects on human health, including the possibility that exposure to such chemicals can be superimposed on traditional risk factors to initiate or exacerbate the development of obesity. BPA is a suspected obesogen, whereas BADGE, described as a peroxisome proliferator–activated receptor gamma (PPARγ) antagonist, could reduce weight gain.Objectives: We sought to test the adipogenic effects of BADGE in a biologically relevant cell culture model.Methods: We used multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of BADGE and BPA and evaluated their effects on adipogenesis, osteogenesis, gene expression, and nuclear receptor activation.Discussion: BADGE induced adipogenesis in human and mouse MSCs, as well as in mouse 3T3-L1 preadipocytes. In contrast, BPA failed to promote adipogenesis in MSCs, but induced adipogenesis in 3T3-L1 cells. BADGE exposure elicited an adipogenic gene expression profile, and its ability to induce adipogenesis and the expression of adipogenic genes was not blocked by known PPARγ antagonists. Neither BADGE nor BPA activated or antagonized retinoid “X” receptor (RXR) or PPARγ in transient transfection assays.Conclusions: BADGE can induce adipogenic differentiation in both MSCs and in preadipocytes at low nanomolar concentrations comparable to those that have been observed in limited human biomonitoring. BADGE probably acts through a mechanism that is downstream of, or parallel to, PPARγ.

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