You eat smartly, you exercise, you ask advice from your doctor. Yet, you still seem to be fighting the battle of the bulge. Sound familiar? I don’t use the f word lightly; but I included it in the title of this post because apparently our battle against fat may be about more than simply calories in versus energy out, more than willpower and sweat. Some of the nation’s top scientists are uncovering chemicals in our environment that have the power to wreck havoc on our metabolism.
One of those top scientists is researcher Christopher Kassotis, PhD, who now works at Duke University. His recent work published in the journal Scientific Reports is helping build upon a body of research that informs the science and medical community about ways of studying this landmark health issue. Here is our conversation about his research:
Q: You are researching how certain substances could be making us fat, and you’re not talking about food. This is a hard concept to grasp. How can this be?
Yes, absolutely. So the endocrine system is intimately important for metabolic health. What researchers have found over the last several years is that there are a group of chemicals (originally termed “obesogens”, now more generally termed “metabolic disruptors”) that can interfere with endocrine signaling as it relates to our metabolism. This can occur through a number of mechanisms. The peroxisome proliferator activated receptor gamma (PPARy) is considered the master regulator of fat cell differentiation in the body, and as it turns out, there are a variety of environmental contaminants (pesticides, flame retardants, plasticizers, etc.) that can bind and turn on this receptor, pushing pre-adipocytes to develop into mature white fat cells and accumulate lipids – increasing both fat cell size and number. Thyroid receptor antagonism, androgen receptor antagonism, retinoid X receptor agonism, glucocorticoid receptor agonism, and other mechanisms are all other pathways through which metabolic health can be disrupted. This is particularly important during critical windows. So exposing animals during gestation to some of these chemicals can permanently alter metabolic health in the offspring – resulting in animals that become overweight even though they may consume the exact same amount of food as non-exposed animals. This can occur through deregulation of insulin signaling, nutrient and fat processing and partitioning, and by influencing feeding and exercise behaviors.
Q: What sort of endocrine disrupting chemicals are you studying? Are these things we are all exposed to, or just people in certain situations?
We are studying a really wide range of endocrine disrupting chemicals. Our lab has done a lot of work in characterizing the wide range of contaminants that are routinely found in indoor house dust. These chemicals leach out of a wide variety of consumer products (electronics, your sofa and other furniture, carpeting/flooring, etc.) and end up accumulating in the dust in your home. We (and other labs) have published a large number of studies now, vacuuming up dust from people’s residential homes and surveying for the presence of large numbers of chemicals (flame retardants, phthalates, phenols, pesticides, perfluorinated chemicals, parabens, etc.) and reporting a large number at a range of concentrations. So when I joined the lab, we knew a variety of these chemicals were able to activate PPARy, and so we suspected they might also cause pre-adipocytes to differentiate into mature fat cells and impact metabolic health of residents. So yes, these are definitely chemicals that everyone is exposed to, for the most part.
Q: Are there certain types of chemicals we can all avoid, just to be on the safe side? Or do we know enough yet about which chemicals could be to blame?
There are certainly ways to influence exposure to these – avoid pesticide use indoors, buy flame retardant free furniture (increasingly easy), purchase a newer TV (the older ones often leach polybrominated diphenyl ethers), opt for wood floors over carpeting, and for more general tips I always suggest that people filter their water with a standard carbon fiber filter (Brita, Pur, other) and always avoid storing and heating food and drink items in plastic wherever possible. Cosmetics can be a large source, though there are a growing number of companies that are being quite transparent about chemicals in their products, etc. There’s still a lot to figure out though, and we’re still working to understand new chemicals that are present in house dust and other commonly encountered environments.
Q: How much more research is needed in this area?
My work focused first on working out a robust method for evaluating potential metabolic disrupting chemicals in a cell model, as we obviously cannot test everything in animals, nor should we. Ideally we want cell models that can screen out chemicals that require further review in higher order systems, and 3T3-L1 cells have proven useful in this regard. So these are mouse embryo cells that are committed to the adipocyte lineage, but are still pre-adipocytes. So they cannot develop into muscle or bone cells, only into fat cells, but they are stuck in a preliminary state and require a push to develop into mature fat cells. So we do this by treating with a known cocktail of chemicals, honed by a variety of researchers over many years, that push these cells essentially right to the edge of differentiation. You can then expose them to your test chemicals and evaluate which ones cause the cells to develop into mature fat cells and accumulate lipids. So my first project, recently published in Scientific Reports: http://www.nature.com/articles/srep42104 evaluated several systems and generally came to the conclusion that many common factors that change between labs really influence the results of this assay to a wide degree. This likely impacts reproducibility of these results between labs, and reinforces that you really need to know your cell system extremely well, and describe it very carefully when you publish papers. My next paper is assessing a wide variety of chemicals that we’ve commonly found in house dust (40+), which is currently under review. Broadly, we found that more than 2/3 of these common chemicals could drive fat cell development at, in some cases, environmentally relevant levels. We’ve gone in a few different directions since then, looking at different classes of contaminants and different mechanisms that might be involved in this process. Ultimately, we’d like to know how these chemicals might impact the metabolic health of residents living in these homes. There’s still a lot to do in this area for sure!
Q: Where can people go to read more about your work?
That’s at http://www.cdkassotis.com.