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

Author

Listed:
  • Bo Wang

    (McMaster University
    McMaster University
    China Agricultural University)

  • Evangelia E. Tsakiridis

    (McMaster University
    McMaster University)

  • Shuman Zhang

    (McMaster University
    McMaster University)

  • Andrea Llanos

    (McMaster University
    McMaster University)

  • Eric M. Desjardins

    (McMaster University
    McMaster University)

  • Julian M. Yabut

    (McMaster University
    McMaster University)

  • Alexander E. Green

    (McMaster University
    McMaster University)

  • Emily A. Day

    (McMaster University
    McMaster University)

  • Brennan K. Smith

    (McMaster University
    McMaster University)

  • James S. V. Lally

    (McMaster University
    McMaster University)

  • Jianhan Wu

    (McMaster University
    McMaster University)

  • Amogelang R. Raphenya

    (McMaster University
    McMaster University)

  • Krishna A. Srinivasan

    (McMaster University
    McMaster University)

  • Andrew G. McArthur

    (McMaster University
    McMaster University)

  • Shingo Kajimura

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Jagdish Suresh Patel

    (University of Idaho
    University of Idaho)

  • Michael G. Wade

    (Health Canada)

  • Katherine M. Morrison

    (McMaster University
    McMaster University)

  • Alison C. Holloway

    (McMaster University
    McMaster University)

  • Gregory R. Steinberg

    (McMaster University
    McMaster University
    McMaster University)

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.

Suggested Citation

  • 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 & Amogel, 2021. "The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25384-y
    DOI: 10.1038/s41467-021-25384-y
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    Cited by:

    1. Yun Han Kwon & Suhrid Banskota & Huaqing Wang & Laura Rossi & Jensine A. Grondin & Saad A. Syed & Yeganeh Yousefi & Jonathan D. Schertzer & Katherine M. Morrison & Michael G. Wade & Alison C. Holloway, 2022. "Chronic exposure to synthetic food colorant Allura Red AC promotes susceptibility to experimental colitis via intestinal serotonin in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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