The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue
| Autor: | James S. V. Lally, Gregory R. Steinberg, Andrew G. McArthur, Evangelia E. Tsakiridis, Brennan K. Smith, Michael G. Wade, Katherine M. Morrison, Julian M. Yabut, Bo Wang, Shuman Zhang, Krishna A Srinivasan, Jagdish Suresh Patel, Alison C. Holloway, Shingo Kajimura, Eric M. Desjardins, Amogelang R. Raphenya, Emily A. Day, Alex E. Green, Andrea Llanos, Jianhan Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Science General Physics and Astronomy 030209 endocrinology & metabolism Food Contamination Biology Diet induced thermogenesis p38 Mitogen-Activated Protein Kinases General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Insulin resistance AMP-Activated Protein Kinase Kinases Adipose Tissue Brown Internal medicine Mitophagy Brown adipose tissue medicine Cyclic AMP Animals Humans Obesity Pesticides Uncoupling Protein 1 030304 developmental biology 0303 health sciences Multidisciplinary Organophosphate AMPK Thermogenesis General Chemistry medicine.disease Thermogenin Mice Inbred C57BL Endocrinology medicine.anatomical_structure chemistry Chlorpyrifos Energy Metabolism Protein Kinases |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discover that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impairs BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This is associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic. Chlorpyrifos is a widely-used pesticide and a common residue on vegetables and fruits. Here the authors show that at non-neurotoxic doses, chlorpyrifos reduces energy expenditure, by inhibiting diet induced thermogenesis, and promotes obesity and insulin resistance. |
| Databáze: | OpenAIRE |
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