The effect of long-term exposure to nonylphenol at environmentally relevant levels on mouse liver and adipose tissue

Exposure to the xenoestrogen nonylphenol (NP) during critical windows of development leads to metabolic abnormalities in adult life. However, less is known about NP exposure outside the developmental period on metabolic outcomes. We investigated the effect of prolonged exposure to NP after sexual maturity and at environmentally relevant concentrations below the 'no observable adverse effects level' (0.5 and 2.5 mg/kg/d). Male Swiss mice fed a normal-fat diet exposed to 2.5 mg/kg/d NP showed reduced weight gain and hepatic fat content. In male and female C57BL/6 mice fed a high-fat diet, NP exposure modified the mRNA levels of estrogen receptor α (Esr1) and adipose lineage markers in a sexually dimorphic and adipose depot-dependent pattern. Moreover, in primary female but not male stromal vascular cells from C57BL/6 mouse inguinal WAT induced to differentiate into adipocytes, NP upregulated Fabp4 expression. Low-level exposure to NP outside critical developmental windows may affect the metabolic phenotype distinctly. DATA AVAILABILITY STATEMENT: All data not included in the manuscript, such as raw results, are available upon request and should be addressed to AAA.