Bisphenol A might make you fat

(This is another archival repost, written for the old blog in 2009.)

If you’ll excuse my tabloid headline writer…

A year ago, I wrote Lies, damn lies, and tissue culture, describing some of the reasons why caution and healthy skepticism are required when assessing the conclusions of tissue culture studies. This is especially the case when the tissue culture studies are being used as part of what Ben Goldacre calls the Daily Mail’s great oncological ontology project of sorting all the world’s inanimate objects into those which cause cancer, and the rest, which surely must cure cancer.

One example I used in that item was Bisphenol A (BPA), a biologically active chemical found in the environment (xenobiotic), including in the plastics used for drinks bottles. Specifically, BPA is thought to be an endocrine disruptor, mimicking some of the effects of the hormone estrogen in the body. Estrogen is known to promote some cancers, particularly breast cancers, and so in the great project BPA looks to be headed for the “causes cancer” box, and regulatory bodies around the world have been keeping on eye on BPA research. Of course, estrogen has roles in several other systems, and another where harmful activity of BPA has been suggested is in fat and sugar metabolism.

So far, much of the research into the effects of BPA on metabolism, and related diseases — such as obesity, diabetes, and cardiovascular disease, collectively, the “metabolic syndrome” — have been very limited in the power of the conclusions which can be drawn from them. Some studies have shown disruption of metabolism by BPA in laboratory animals,[1] but there are important differences in this system between laboratory animals and humans.[2] Many additional studies have have shown BPA interfering with signaling pathways in tissue culture, but as previously described, effects seen in tissue culture do not always represent important effects in the human body. A large portion of studies into effects of BPA, either in animals or culture, suffer from the additional limitation that when they do detect such effects, it is at a concentration much higher than would ever be seen in the human body. But the issue is surely one that deserves investigation: though any effect of BPA on the metabolic syndrome is likely to be small compared to diet and exercise, in the current epidemic situation, it could still be important.

A paper from m’colleagues in Cincinnati takes a step towards overcoming the limitations of earlier work and further establishing both the effect of BPA on fat metabolism, and the mechanism for this effect. Eric Hugo et al[3] looked at the effects that physiologically relevant concentrations of BPA on the release of adiponectin, a key metabolism regulating hormone, in human surgical explants of adipose (fat storage) tissue. In the body, adiponectin is secreted into the blood by the adipocyte cells which make up adipose tissue, and the hormone’s blood concentration is inversely correlated with body fat percentage. Indeed, it has been established that adiponectin regulates fat and glucose metabolism, and also affects insulin sensitivity and resistance.[4][5] Adiponectin is therefore a good marker to study as a surrogate measure for body fat percentage, obesity, and diabetes.

So Hugo, et al, took a number of surgical explants from both obese and non-obese patients who had surgery for either breast reduction, abdominoplasty (“tummy tuck”), or gastric bypass. They put small lumps of the fat tissue (sadly, no photographs in the paper) into dishes of culture medium, and then subjected these to various concentrations of either BPA, or for comparison, either the principal form of estrogen (estradiol), or a chemical called ICI which destroys estrogen receptors (the molecules in the cell which BPA and estrogen interact with in order to have downstream effects). After six hours of exposure, the culture media was taken for analysis to see how much adiponectin had been secreted by the tissue.

There are a number of methods by which a specific protein can be detected and quantified in such a sample. The particular method chosen this study was an “Enzyme-Linked ImmunoSorbent Assay” (ELISA). In an ELISA, you take a plastic plate containing an array of mini “test tubes”, or wells, and attach an antibody — a protein which recognises and affixes to a specific other protein, in our case to adiponectin — to the plastic wells. The wells are then filled with the experiment samples, and a second antibody with specificity to the same specific protein, but to a different section of the protein is washed over the wells. That second antibody is attached to a fluorescent chemical, which can later be easily quantified. So to recap, in this case, the adiponectin in each sample would be affixed to its well via the first antibody, and when the second antibody, with its fluorescent flag, is washed over the well, it will also become affixed if it finds an adiponectin to attach itself to, creating an antibody-adiponectin sandwich. Ultimately, the more adiponectin in the sample, the more fluorescent flag in the well.

So what did Hugo et al find? Most importantly, they found that estrogen and BPA both suppressed release of adiponectin from the explants, both of breast and abdominal tissue. Interestingly, this effect was clear for low concentrations of BPA, of the sort that might be commonly found in these tissues in the human body, but it disappeared at much higher concentrations. Indeed, at the most environmentally relevant concentrations, BPA was at least as efficient as estrogen in blocking adiponectin release. In most systems which involve BPA and estrogen, the principal cellular effects of these chemicals occur via activation of the estrogen receptors, so what happened when the tissues were treated with ICI, the chemical which is thought to destroy estrogen receptors? One might assume that ICI would have an opposite effect to the estrogen receptor activators, but intriguingly, it appeared actually to have similar effects of inhibition in several of the patients, highlighting that cell signalling is never the simple story we would like it to be. Perhaps it is not “active” estrogen receptor which is required for suppression of adiponectin release, but “inactive” estrogen receptor which is required to maintain normal levels of secretion? Perhaps the effects are not mediated by estrogen receptors at all, or perhaps it is a more complicated story still.

So, this new work adds weight to the hypothesis that BPA can contribute to disruption of metabolism, obesity, and diabetes. But the work is far from powerful enough to close the case on the issue. Like earlier work, the research reported here suffers from a number of limitations. For each category, less than ten patients were studied, mostly women: this is far too few to make general conclusions. This limitation is emphasised by the fact that in the tissue samples, levels of adiponectin release varied as much as ten-fold between patients — perhaps as a result of genetics, sex, age, lifestyle, or pure chance. Additionally, this study only looks at a surrogate measure — adiponectin release — rather than real issue of disease incidence; and the surgical explants, though more realistic than tissue culture or animal models, are still not a perfect reflection of what happens in the human body. But the work does contribute to a body of evidence which makes the case for taking the research to the next stage: a study that looks for patterns in a population of hundreds of individuals.


  1. Heindel JJ. 2003. Endocrine disruptors and the obesity epidemic. Toxicol Sci 76:247–249. full text
  2. Ben Jonathan N, LaPensee CR, LaPensee EW. 2008. What can we learn from rodents about prolactin in humans? Endocr Rev 29:1–41. doi
  3. Eric R. Hugo, Terry D. Brandebourg, Jessica G. Woo, Jean Loftus, J. Wesley Alexander, Nira Ben-Jonathan (2008). Bisphenol A at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes Environmental Health Perspectives, 116, 1642-1647 DOI: 10.1289/ehp.11537
  4. Ukkola O, Santaniemi M. 2003. Adiponectin: a link between excess adiposity and associated comorbidities? J. Mol. Med. 80 (11): 696–702. doi
  5. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. 2004. Adiponectin and metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 24 (1): 29–33. doi

Declaration of interests: I used to work with three of the authors of the paper, but had nothing to do with this project or paper.

Leave a comment

Your email address will not be published. Required fields are marked *