Nieminen, P, P Lindström-Seppä, A-M Mustonen, H Mussalo-Rauhamaa, and JVK Kukkonen. 2002. Bisphenol A Affects Endocrine Physiology and Biotransformation Enzyme Activities of the Field Vole (Microtus agrestis). General and Comparative Endocrinology 126: 183–189.

other work on BPA and weight homeostasis

This paper presents preliminary suggestions that biphenol A may alter circulating levels of ghrelin and leptin in wild mice. The experiment was done in a way that does not allow testing for statistical significance of the results. Hence all that can be concluded is that more attention should focus on the role of compounds like BPA in disrupting the hormonal control of weight regulation.

What did they do? Nieminen et al. exposed sexually mature mice to three different levels of bisphenol A and measured circulating plasma levels of testosterone, ghrelin, leptin, estradiol, cortisol, luteinizing hormone (LH)and thyroid stimulating hormone (TSH); and activity levels of several liver and kidney enzymes. Exposure levels for BPA were 10, 50, 0r 250 mg/kg, injected subcutaneously. The mice were born to parents that had been caught in the wild.

The experiment ran for 5 days, with injections the first 4. On the fifth, the animals were sacrificed and examined. Blood samples and tissue samples were taken immediately and after brief processing, stored in liqud nitrogen.

The serum samples obtained were too small to allow determination of estradiol, LH, TSH, leptin, ghrelin and cortisol for individual animals, so samples were pooled. This prevented statistical testing for differences between treatment and control.

What did they find? While none of the control animals died, 10 of the treated animals did, at least one from each exposure level, indicating that these exposure levels are relatively high.

Hormone measurements suggested trends in response to increases in BPA exposure. Plasma testosterone levels increased significantly. T4 levels did not change. For the hormones whose analysis was based on pooled samples, leptin levels appeared to decrease while ghrelin appeared to increase. TSH did not change.

What does it mean? Very little can be concluded about endocrine disruption from these experiments. The deaths of treated animals at these exposure levels indicate that wild mice of this species are more sensitive to BPA than lab rats, for which comparable exposures would not lead to mortality.

This is the first report (contact me if I am incorrect) of any study examining disruption of either leptin or ghrelin hormone systems. The results are consistent with an impact, but because of the statistical analysis nothing can be concluded. That is unfortunate, because research into factors disrupting weight homeostasis are greatly needed.

The world is experiencing a global epidemic of obesity. Hormonal control of weight homeostasis is a complex process involving a series of hormonal systems. Indications like this that some of these systems may be vulnerable to disruption should be pursued vigorously, particularly on health issues of such global import. One of the recurring lessons of research into endocrine disruption is that virtually all chemically-mediated signaling systems are vulnerable.

Ghrelin and leptin are two of the hormone systems important to weight homeostasis: secreted by the stomach, ghrelin increases food intake and decreases fat breakdown (lipolysis). Leptin is produced by fat cells. Normally more fat leads to more leptin, which then represses appetite and increases basal metabolic rate. The direction of BPA's impact on these two systems (leptin down, ghrelin up) suggested by Nieminen et al.'s work is thus consistent with a pattern that would lead to weight gain. Their experiments ran only a short time, however.

It would make more sense for the initial entry into this research field to focus on in utero exposures at low levels, not high level exposures of adults. Howdeshell's work, for example, on changes in the rate of sexual development following in utero exposure to BPA were conducted at exposure levels 1000-times lower; and indeed she found a significant effect of in utero exposure on pubertal weight: exposed animals were significantly heavier. That study did not examine either ghrelin or leptin levels; indeed ghrelin had not even been discovered.