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FEBS J. 2006 Apr;273(7):1362-72.

Benzo[a]pyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant.

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1
JE2482 Lipidomix, Institut National Polytechnique de Lorraine, Vandoeuvre-lès-Nancy, France.

Abstract

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 microm). Lipolysis induced by beta(1)-, beta(2)- and beta(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 microm). 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.

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