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
| Autor: | Philippe Irigaray, Virginie Ogier, Sandrine Jacquenet, Pierre Sibille, Veronique Notet, Luc Méjean, Frances T. Yen, Bernard Bihain |
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| Přispěvatelé: | Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Institut National Polytechnique de Lorraine (INPL), Polyclinique de Gentilly |
| Předmět: |
Male
medicine.medical_specialty Epinephrine ADIPOCYTE Population Adipose tissue Food Contamination [SDV.BC]Life Sciences [q-bio]/Cellular Biology Fatty Acids Nonesterified 010501 environmental sciences Weight Gain 01 natural sciences Biochemistry Body Mass Index Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine Receptors Adrenergic beta LIPOLYSE Benzo(a)pyrene medicine Animals Humans Lipolysis Receptor education Molecular Biology Carcinogen 030304 developmental biology 0105 earth and related environmental sciences 2. Zero hunger 0303 health sciences education.field_of_study Chemistry Body Weight Cell Biology Adrenergic beta-Agonists 3. Good health Mice Inbred C57BL Endocrinology Adipose Tissue 13. Climate action Toxicity Ex vivo |
| Zdroj: | HAL FEBS Journal FEBS Journal, Wiley, 2006, 273 (7), pp.1362-1372 |
| ISSN: | 1742-464X 1742-4658 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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