Alliance between the thyroid hormone receptor and obesogens: Current apprehensions and emerging perspectives on the endocrine origins of obesity.

Thyroid hormone receptors (THR) are central regulators of metabolic balance, governing lipid and glucose homeostasis, basal metabolic rate, and adipogenesis. Dysregulated thyroid hormone signaling can lead to persistent metabolic consequences. Metabolic-disrupting chemicals (MDCs) are increasingly implicated in metabolic dysfunction and the global rise in obesity. By interfering with hormonal signaling, MDCs disrupt tightly regulated metabolic processes. A distinct subgroup of MDCs, known as obesogens, directly promotes weight gain by altering energy homeostasis, glucose and lipid metabolism, adipocyte differentiation, and intracellular metabolic signaling. These compounds are widely present in food packaging, plastics, cosmetics, pesticides, and food contaminants like dioxins and polychlorinated biphenyls. Exposure to obesogens during critical developmental windows, particularly prenatal and early postnatal life, can induce long-term metabolic reprogramming, increasing susceptibility to obesity later in life. Emerging evidences indicate that obesogens can disrupt the hypothalamic-pituitary-thyroid (HPT) axis and impair THR function. However, the precise pathophysiological mechanisms linking obesogen-induced THR disruption to obesity remain ill-defined. In this review, we discuss current evidence on the role of obesogens in thyroid dysfunction and obesity pathogenesis, emphasizing that THRs are critical molecular targets in environmentally induced metabolic disorders, and explore their potential as strategic points for disease prevention and therapeutic interventions.