BPA and a common phthalate may contribute to obesity, predicts a cell test.

Sep 15, 2010

Wang, Y.-F., H-R. Chao, C-H. Wu, C-H Tseng, Y-T Kuo and T-C Tsou. 2010. A recombinant peroxisome proliferator response element-driven luciferase assay for evaluation of potential environmental obesogens.  Biotechnology Letters http://dx.doi.org/10.1007/s10529-010-0359-9.

Synopsis by Laura Vandenberg

Two widely used chemicals are implicated in obesity after they reacted with specially-made cells and influenced fat cell development and fat storage – two underlying factors in weight gain.

Chemicals that can influence obesity may now be easier to identify, thanks to a new cell test that can pinpoint the guilty compounds. Using the test, researchers identified two common environmental chemicals – bisphenol A and benzyl butyl phthalate – that can modulate the signals controlling the number of fat cells produced and the uptake and storage of fats in those cells.

Both of these conditions – more fat cells and fatter cells – underlie weight gain in people. Until now, there was no easy way to predict if a chemical could alter cell function to cause obesity. The newly developed cell line may be helpful for screening large numbers of environmental chemicals that could be selected for future study or to identify heavily-used chemicals that need stricter regulation.

Obesity is increasing around the world, leading some researchers and public health officials to call it an epidemic. As a health issue, obesity can lead to a wide variety of life threatening conditions, including diabetes and heart disease. Most scientists and medical experts would agree that eating habits and decreased exercise have contributed to this alarming trend. But, chemicals in the environment can also induce obesity, according to a growing body of research that implicates components of plastics, pesticides and flame retardants. These chemicals are called obesogens.

To test for chemicals that might influence weight gain, the researchers created an indicator cell containing a specific type of molecule called a peroxisome proliferator-activated receptor (PPAR). A chemical could be an obesogen if it binds to PPAR because PPAR controls how cells use and store energy. Normally, PPAR signals cells to 1) develop into a fat cell, 2) start storing fat and/or 3) stop breaking down the fat it has already stored.

Interactions between PPAR and the chemicals were determined by measuring the amount of light that passed through the indicator cells. More light meant the chemical may be an obesogen because it bound and activated the PPAR.

Five environmental chemicals were tested with the indicator cells to determine if they interacted with PPAR. They included the compounds benzyl butyl phthalate (BBP), dipropyl phthalate (DPP) and bisphenol A (BPA); the poisonous herbicide dioxin (or TCDD); and a product of cooking oil fumes, tt-DDE. These chemicals were chosen because humans are widely exposed to them. They were also previously identified as endocrine disruptors – chemicals that can alter the way the body handles hormones, including hormones that control body weight.

Two of these chemicals, BPA and BBP, bound to PPAR and produced a significant reaction, suggesting that they may be obesogens. The other three did not bind PPAR.

The next step was to determine if BBP and BPA could actually change fat metabolism. Cells called 3T3-L1 cells – which can become a fat cell under the right conditions – were exposed to either BPA or BBP. After exposure, fat droplets started to accumulate in the 3T3-L1 cells. This suggests that these chemicals can induce the development of fat cells.

BBP was used previously in children's toys and continues to be used in flooring materials. Phthalate exposure has been linked to a host of problems in exposed infants, including altered development of the male reproductive tract, susceptibility to allergies and asthma, changes in birth weight, and altered behaviors, including hyperactivity. The European Union and the United States banned BBP from children's products.

BPA is found in a variety of consumer products, including some polycarbonate baby bottles, most carbonless paper receipts and the linings of food and beverage cans. Exposure to small amounts of this chemical has been implicated in a large number of developmental problems, including altered development of the brain and behaviors, malformations of the male and female reproductive tract, and altered metabolism and body weight. Regulations to limit its use in some children's products are being considered in several U.S. states and limited bans have passed in Minnesota, Connecticut and Canada.