Dietary Exposure to the Endocrine Disruptor Tolylfluanid Promotes Global Metabolic Dysfunction in Male Mice

• DOI: 10.1210/en.2014-1668
• Publication Date: 2014-12-23T16:53:44Z
• Authors: Shane M. Regnier; Andrew G. Kirkley; Honggang Ye; Essam El-Hashani; Xiaojie Zhang; Brian A. Neel; Wakanene Kamau; Celeste C. Thomas; Ayanna K. Williams; Emily T. Hayes; Nicole L. Massad; Daniel N. Johnson; Lei Huang; Chunling Zhang; Robert M. Sargis
• Keywords: Endocrine disruptor

Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous vitro ex vivo work has identified it potent disruptor with capacity promote adipocyte differentiation induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings an mouse model dietary TF exposure. After 12 weeks consumption normal chow diet supplemented 100 parts per million TF, mice exhibited increased body weight gain increase total fat mass, specific augmentation visceral adipose depots. This accumulation proposed occur through reduction lipolytic fatty acid oxidation gene expression. Dietary exposure induced glucose intolerance, inflexibility, while also disrupting diurnal rhythms energy expenditure food consumption. Adipose tissue function was impaired serum adiponectin levels. Moreover, adipocytes TF-exposed reduced sensitivity, effect mediated down-regulation substrate-1 expression, mirroring Finally, set enrichment analysis revealed signaling treatment. Taken together, identify novel obesogen mice, leading alterations homeostasis that recapitulate many features syndrome.