Potential Obesogen Identified: Fungicide Triflumizole Is Associated with Increased Adipogenesis in Mice. Valerie Brown Environmental Health Perspectives Dec 3, 2012 http://ehp.niehs.nih.gov/2012/12/120-a474a/[Excerpted] Obesogens are chemicals that increase either the number of fat cells in an organism or the amount of fat stored in those cells. Obesogens may also act indirectly on obesity by modulating appetite, satiety, or metabolism. Now researchers have identified a common agricultural chemical that appears to qualify as an obesogen because it nudges gene expression and stem cell differentiation toward becoming a fat cell [EHP 120(12):1720–1726; Li et al.].
In the current study, investigators exposed human and mouse mesenchymal stem cells (MSCs) and preadipocytes to triflumizole (TFZ), a fungicide widely used on food and ornamental crops. MSCs can differentiate into bone, cartilage, or fat cells; preadipocytes are precursor fat cells that mature into adipocytes in response to environmental cues. The investigators found that expression of obesity-related genes increased in treated cells from both species, and that lipid accumulation and expression of obesity-related genes increased in treated cells from both species.
The team then exposed three groups of pregnant mice to three different doses of TFZ and examined fat tissues and gene expression profiles of the offspring.... The lowest dose was 400 times lower than the established no-observed-adverse-effect level for TFZ exposure in rodents.
The authors observed that induced cultured MSCs from the exposed offspring appeared to be more likely to become fat cells than bone cells....
Triflumizole Is an Obesogen in Mice that Acts through Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Xia Li, Hang T. Pham, Amanda S. Janesick, and Bruce BlumbergEnviron Health Perspect 120:1720–1726 (2012). http://ehp.niehs.nih.gov/2012/12/1205383/
Objectives: We sought to test the ability of TFZ to activate PPARγ and promote adipogenesis in vitro and in vivo.
Methods: We used transient transfection to test the ability of TFZ to activate PPARγ, and we used 3T3-L1 preadipocytes and human multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of TFZ in culture. We treated pregnant mice with three doses of TFZ and evaluated the effects on body weight, adipose depot weight, and MSC programming in the prenatally exposed offspring.
Discussion: TFZ induced adipogenesis in MSCs and in mouse 3T3-L1 preadipocytes. Prenatal exposure to levels of TFZ at approximately 400-fold below the reported no observed adverse effect level increased adipose depot weight. All doses of TFZ tested increased adipogenic gene expression in MSCs while inhibiting expression of osteogenic genes.
Conclusions: TFZ acts through a PPARγ-dependent mechanism to induce adipogenic differentiation in MSCs and preadipocytes at low nanomolar concentrations. Prenatal TFZ exposure increases adipose depot weight and diverts MSC fate toward the adipocyte lineage; therefore, we conclude that TFZ is an obesogen in vivo.