The EDC mixture ‘NeuroMix’ Alters Neuroendocrine Physiology, Fatty Food Preference, and the Central Reward Transcriptome

Obesity prevalence has risen dramatically in recent decades, coincident with increasing human exposures to endocrine-disrupting chemicals (EDCs). Many EDCs act as "obesogens" by promoting adipogenesis and disrupting metabolism; however, little is known about their effects on neural circuits that regulate food reward and motivation. EDCs cause neurobiological and behavioral changes, implicating them in central energy balance regulation. In this experiment, we tested whether developmental exposure to the environmentally relevant EDC mixture NeuroMix (NMX) may have obesogenic-like effects in rats through central mechanisms. Using a dose-response approach, male and female rats were exposed perinatally to NMX (0, 0.1X, 1X, 10X doses) and assessed for adult high-fat food and sucrose preference, thyroid hormones, and transcriptomics in reward and hypothalamic nuclei. Females exposed to the 1X dose exhibited a nonmonotonic increase in fatty food preference and consumption accompanied by appreciable weight gain. Males showed reduced thyroid hormone levels at the highest 10X dose. NMX antagonized thyroid hormone receptor β in vitro, suggesting a potential molecular mechanism underlying the observed neuroendocrine effects. Transcriptomic analyses in 1X rats identified the nucleus accumbens (NAc) as a key neural substrate in both sexes, with spliceosomal complex eigengenes in the NAc acting as correlates of high fat food behaviors, and individual splicing factors emerging as possible neuromolecular mechanisms linking endocrine disruption to obesogenic eating. Together, this research demonstrates that environmentally relevant EDC mixtures exert sex- and dose-specific effects on food choice, thyroid hormones, and gene expression, highlighting neuromolecular reward mechanisms as potential contributors to environmentally mediated obesity risk.