Perinatal exposure to tributyltin affects feeding behavior and expression of hypothalamic neuropeptide Y in the paraventricular nucleus of adult mice

Organotins such as tributyltin chloride (TBT), are highly diffused environmental pollutants, which act as metabolism disrupting chemicals, i.e. may interfere with fat tissue differentiation, as well as with neuroendocrine circuits, thus impairing the control of energetic balance. We have previously demonstrated that adult exposure to TBT altered the expression of neuropeptides in the hypothalamus. In this study, we orally administered daily a solution containing oil, or TBT (0.25, 2.5, or 25 μg/kg body weight/day) to pregnant females from gestational day 8 until birth, and to their pups from day 0 until post‐natal day 21. Our results showed that TBT exposure of female mice during gestation and of pups during lactation permanently altered the feeding efficiency of pups of both sexes and subcutaneous fat distribution in adult males. In addition, the neuropeptide Y system was affected at the level of the paraventricular nucleus, with a decrease in immunoreactivity in both sexes (significant in females for all TBT doses and in males only for intermediate TBT doses), while no effect was observed in other hypothalamic areas (arcuate, ventromedial and dorsomedial nuclei). Metabolic syndrome, as well as obesity and diabetes, which are significant health issues, are considered multifactorial diseases and may be caused by exposure to metabolic disruptors, both in adults and during perinatal life. In addition, our work indicates that TBT doses defined as the tolerably daily intake had a profound and sex‐specific long‐term effect

Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food Intake and Energy Metabolism

The metabolism-disrupting chemicals (MDCs) are molecules (largely belonging to the category of endocrine disrupting chemicals, EDCs) that can cause important diseases as the metabolic syndrome, obesity, Type 2 Diabetes Mellitus or fatty liver. MDCs act on fat tissue and liver, may regulate gut functions (influencing absorption), but they may also alter the hypothalamic peptidergic circuits that control food intake and energy metabolism. These circuits are normally regulated by several factors, including estrogens, therefore those EDCs that are able to bind estrogen receptors may promote metabolic changes through their action on the same hypothalamic circuits. Here, we discuss data showing how the exposure to some MDCs can alter the expression of neuropeptides within the hypothalamic circuits involved in food intake and energy metabolism. In particular, in this review we have described the effects at hypothalamic level of three known EDCs: Genistein, an isoflavone (phytoestrogen) abundant in soy-based food (a possible new not-synthetic MDC), Bisphenol A (compound involved in the manufacturing of many consumer plastic products), and Tributyltin chloride (one of the most dangerous and toxic endocrine disruptor, used in antifouling paint for boats)

Neuroendocrine circuits controlling food intake: a target for endocrine disruptors

Tributyltin (TBT), a pesticide used in antifouling paints, is toxic for aquatic invertebrates. In vertebrates, TBT may act in obesogen- inducing adipogenetic gene transcription for adipocyte differentiation (1). In a previous study, we demonstrated that acute administration of TBT induces c-fos expression in the arcuate nucleus (2). Therefore, in this study, we tested the hypothesis that adult exposure to TBT may alter a part of the nervous pathways controlling animal food intake (3). In particular, we investigated the expression of neuropeptide Y (NPY) immunoreactivity. This neuropeptide forms neural circuits dedicated to food assumption and its action is mediated by Y1 receptors that are widely expressed in the hypothalamic nuclei responsible for the regulation of food intake and energy homeostasis. To this purpose, TBT was orally administered at a dose of 0.025 mg/kg/day/body weight to adult animals [male and female C57BL/6 (Y1-LacZ transgenic mice] for 4 weeks. No differences were found in body weight and fat deposition, but we observed a significant increase in feed efficiency in TBT-treated male mice and a significant decrease in circulating leptin in both sexes. Computerized quantitative analysis of NPY immunoreactivity and Y1-related b-galactosidase activity demonstrated a statistically significant reduction in NPY and Y1 transgene expression in the hypothalamic circuit controlling food intake of treated male mice in comparison with controls. In conclusion, the present results indicate that adult exposure to TBT is profoundly interfering with the nervous circuits involved in the stimulation of food intake