Evidences of Metabolic Disruptor Hypothesis: Phytoestrogens and BPA

STOKER, CORA; RAMOS, J. GUILLERMO; ANDREOLI M. F.

Buenos Aires

Congreso; III Internacional Congress of Translational Medicine; 2016

Obesity poses a major threat to the health of the population of most countries of the world and results from prolonged imbalance between energy intake and energy expenditure. It is a chronic, progressive and multifactorial metabolic disease associated with many diseases that lead to premature disability and mortality. The etiology of obesity involves numerous factors that can be defined as hereditary, congenital, social and cultural. There is growing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent global increase in adult obesity.The brain has emerged as the key regulator of appetite. It receives and integrates a variety of signals to produce an overall response of hunger or satiety. The arcuate nucleus in the hypothalamus is the central area involved in the control of food intake.Estrogens play a fundamental role in the control of energy homeostasis and glucose metabolism in health and metabolic diseases. They act in hypothalamic nuclei to differentially control food intake, energy expenditure, and white adipose tissue distribution. Estrogen actions in skeletal muscle, liver, adipose tissue, and immune cells are involved in insulin sensitivity as well as prevention of lipid accumulation and inflammation. Estrogen deficiency promotes metabolic dysfunction, predisposing one to obesity, metabolic syndrome, and type 2 diabetes.Endocrine disrupting chemicals (EDCs) are a subclass of toxic chemicals that act by altering some aspect of hormone action. Animal and human exposure data show that a variety of EDCs can act as ?obesogens?, during development with exposures during critical periods in organogenesis, around puberty and in adulthood being related to an increase in central fat deposition and function.Our group studies the effects of some EDCs, like phytoestrogens and bisphenol A, in the neuroendocrine mechanisms regulating food intake.Phytoestrogens are nonsteroidal compounds found in many legumes and are particularly abundant in soy products. Phytoestrogens have the capacity to bind both estrogen receptors (ER) α and β and to mimic estrogenic actions. Because both ERs are present in tissues responsible for the regulation of metabolism (hypothalamus, adipose tissue, skeletal muscle, pancreatic β-cells), the implication that phytoestrogens regulate metabolism appears plausible. There is also increasing evidence that phytoestrogens counteract the cellular derangements that are responsible for the development of obesity and metabolic syndrome. We demonstrate that removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen?high fat diet intake.Bisphenol A (BPA) is a compound used in the polymerization of polycarbonate plastics and is an endocrine disrupter. We demonstrate that perinatal exposure to BPA impairs glucose homeostasis, induces obesity and increases food intake in adult life of male rats altering hypothalamic signals. The metabolic disruptor hypothesis proposes that EDCs can act during development predisposing to obesity or metabolic syndrome later in life. Evidences showed in our work support this hypothesis.