The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue

Bo Wang, Evangelia E. Tsakiridis, Shuman Zhang, Andrea Llanos, Eric M. Desjardins, Julian M. Yabut, Alexander E. Green, Emily A. Day, Brennan K. Smith, James S. V. Lally, Jianhan Wu, Amogelang R. Raphenya, Krishna A. Srinivasan, Andrew G. McArthur, Shingo Kajimura, Jagdish Suresh Patel, Michael G. Wade, Katherine M. Morrison, Alison C. Holloway and Gregory R. Steinberg ()
Additional contact information
Bo Wang: McMaster University
Evangelia E. Tsakiridis: McMaster University
Shuman Zhang: McMaster University
Andrea Llanos: McMaster University
Eric M. Desjardins: McMaster University
Julian M. Yabut: McMaster University
Alexander E. Green: McMaster University
Emily A. Day: McMaster University
Brennan K. Smith: McMaster University
James S. V. Lally: McMaster University
Jianhan Wu: McMaster University
Amogelang R. Raphenya: McMaster University
Krishna A. Srinivasan: McMaster University
Andrew G. McArthur: McMaster University
Shingo Kajimura: Beth Israel Deaconess Medical Center and Harvard Medical School
Jagdish Suresh Patel: University of Idaho
Michael G. Wade: Health Canada
Katherine M. Morrison: McMaster University
Alison C. Holloway: McMaster University
Gregory R. Steinberg: McMaster University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25384-y

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