Benzo[ a ]pyrene impairs β‐adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice

Benzo[ a ]pyrene (B[ a ]P) is a common food pollutant that causes DNA adduct formation and is carcinogenic. The report of a positive correlation between human plasma B[ a ]P levels and body mass index, together with B[ a ]P's lipophilicity, led us to test for possible adverse effects of B[ a ]P on adipose tissue. In ex vivo experiments using primary murine adipocytes, B[ a ]P rapidly (within minutes) and directly inhibited epinephrine‐induced lipolysis (up to 75%) in a dose‐dependent manner. Half‐maximum inhibition was obtained with a B[ a ]P concentration of 0.9 mg·L −1 (3.5 µ m ). Lipolysis induced by β 1 ‐, β 2 ‐ and β 3 ‐adrenoreceptor‐specific agonists, as well as ACTH, were also significantly inhibited by B[ a ]P, whereas forskolin‐induced lipolysis was not B[ a ]P‐sensitive. Similar inhibition of catecholamine‐induced lipolysis by B[ a ]P was also seen in isolated human adipocytes; half‐maximum inhibition of lipolysis was achieved with a B[ a ]P concentration of 0.02 mg·L −1 (0.08 µ m ). In vivo treatment of C57Bl/6J mice with 0.4 mg·kg −1 B[ a ]P inhibited epinephrine‐induced release of free fatty acids by 70%. Chronic exposure of mice to B[ a ]P (0.5 mg·kg −1 injected i.p. every 48 h) for 15 days also decreased lipolytic response to epinephrine and induced a 43% higher weight gain compared with controls (B[ a ]P: 2.23 ± 0.12 g versus control: 1.56 ± 0.18 g, P  < 0.01) due to increased fat mass. The weight gain occurred consistently without detectable changes in food intake. These results reveal a novel molecular mechanism of toxicity for the environmental pollutant B[ a ]P and introduce the notion that chronic exposure of human population to B[ a ]P and possibly other polycyclic aromatic hydrocarbons could have an impact on metabolic disorders, such as obesity.