A ubiquitous organophosphate flame retardant disrupts energy and glucose homeostasis in mice

Organophosphate flame retardants (OPFRs) are used in many consumer products, and their presence in our environment raises concerns about potential health dangers. In humans, exposure to OPFRs, such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is associated with metabolic disorders such as obesity, hyperglycemia, and insulin resistance. Our current study seeks to determine how TDCPP exposure affects body composition, glucose homeostasis, and energy balance in a rodent model. C57Bl/6 J mice were divided into two weight-matched groups and fed purified low phytoestrogen diets containing either 0.1 % DMSO (control) or TDCPP 415 mg/kg resulting in an approximate exposure of 50 mg/kg/day. Both male and female mice were used. Promethion metabolic cages were used to measure the rates of oxygen consumption and CO₂ generation, food intake, and locomotion. Body composition was measured using nuclear magnetic resonance relaxometry. Mice underwent a glucose tolerance test, and hyperinsulinemic euglycemic clamp was used to assess insulin sensitivity. Male TDCPP-treated mice showed higher food intake and energy expenditure without changes in locomotion or energy balance. TDCPP tended to differentially affect respiratory exchange ratio, which was increased in males and decreased in females. Male mice showed impaired glucose tolerance, whereas female mice did not. Hyperinsulinemic clamp revealed no significant decrease in the glucose infusion rate of TDCPP-exposed animals. However, hepatic glucose production during hyperinsulinemia was increased compared to controls signifying liver-specific insulin resistance. This study supports the cause for concern related to detrimental metabolic health effects of TDCPP exposure.