The obesogen hypothesis: a shift of focus from the periphery to the hypothalamus.

The obesogen concept proposes that environmental contaminants may be contributing to the epidemic of obesity and its related pathology, metabolic disorder. The first references to such a notion appeared at the beginning of the current decade, with the hypothesis that the correlation between increasing incidence of obesity and enhanced industrial chemical production was not simply coincidental, but potentially causally related. The next event was the introduction of the term "obesogen" as representing an environmental pollutant that adversely affects various aspects of adipose tissue functions. More recently, the concept was extended to include substances that may modify metabolic balance at the central, hypothalamic level. The actions of two prime candidate obesogens, tributyltin (TBT) and tetrabromobisphenol A (TBBPA), acting at the central level are the main focus of this review. Having discussed the evidence for contaminant accumulation in the environment and in human tissues and the potential mechanisms of action, data are provided showing that these two widespread pollutants modify hypothalamic gene regulations. Our studies are based on maternal exposure and measurement of effects in the progeny, mainly based on in vivo gene reporter assays. Such models are obviously pertinent to testing current hypotheses that propose that early exposure might exert effects on later development and physiological functions. The potential molecular mechanisms involved are discussed, as are the broader physiological consequences of these hypothalamic dysregulations.