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.
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.
Irigaray
Philippe
P
JE2482 Lipidomix, Institut National Polytechnique de Lorraine, Vandoeuvre-lès-Nancy, France.
Ogier
Virginie
V
Jacquenet
Sandrine
S
Notet
Véronique
V
Sibille
Pierre
P
Méjean
Luc
L
Bihain
Bernard E
BE
Yen
Frances T
FT
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000494:pharmacology; D015992:Body Mass Index; D001835:Body Weight; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005506:Food Contamination; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015430:Weight Gain
D000318:Adrenergic beta-Agonists; D005230:Fatty Acids, Nonesterified; D011943:Receptors, Adrenergic, beta; D001564:Benzo(a)pyrene; D004837:Epinephrine