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DOI	10.1038/s41467-021-25384-y
	The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue
	Wang B.; Tsakiridis E.E.; Zhang S.; Llanos A.; Desjardins E.M.; Yabut J.M.; Green A.E.; Day E.A.; Smith B.K.; Lally J.S.V.; Wu J.; Raphenya A.R.; Srinivasan K.A.; McArthur A.G.; Kajimura S.; Patel J.S.; Wade M.G.; Morrison K.M.; Holloway A.C.; Steinberg G.R.
发表日期	2021
ISSN	2041-1723
卷号	12 期号:1
英文摘要	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. © 2021, The Author(s).
语种	英语
scopus关键词	acetylcholinesterase; chlorpyrifos; cyanopindolol; cyclic AMP; cytochrome c oxidase; fat droplet; hormone sensitive lipase; hydroxymethylglutaryl coenzyme A reductase kinase; insulin; isoprenaline; messenger RNA; mitogen activated protein kinase p38; propranolol; protein kinase; triacylglycerol; uncoupling protein 1; AMP-activated protein kinase kinase; chlorpyrifos; cyclic AMP; mitogen activated protein kinase p38; pesticide; protein kinase; uncoupling protein 1; chlorpyrifos; concentration (composition); inhibition; muscle; obesity; organophosphate; protein; rodent; animal cell; animal experiment; animal model; Article; basal metabolic rate; body mass; body weight gain; brown adipocyte; brown adipose tissue; caloric intake; controlled study; energy expenditure; enzyme activation; enzyme activity; fasting; fat mass; fatty acid blood level; fatty acid oxidation; food intake; glucose intolerance; glucose tolerance; human; human cell; insulin resistance; insulin sensitivity; lipid diet; liver weight; mitochondrial membrane potential; mitochondrial respiration; mitophagy; mouse; nonalcoholic fatty liver; nonhuman; obesity; observation; oxidative phosphorylation uncoupling; oxygen consumption; promoter region; RNA sequencing; thermogenesis; transmission electron microscopy; animal; brown adipose tissue; C57BL mouse; drug effect; energy metabolism; food contamination; genetics; male; metabolism; obesity; pathophysiology; thermogenesis; Rodentia; Adipose Tissue, Brown; Animals; Chlorpyrifos; Cyclic AMP; Energy Metabolism; Food Contamination; Humans; Male; Mice; Mice, Inbred C57BL; Obesity; p38 Mitogen-Activated Protein Kinases; Pesticides; Protein Kinases; Thermogenesis; Uncoupling Protein 1
来源期刊	Nature Communications
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250631
作者单位	Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON, Canada; State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China; Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States; Institute for Modeling Collaboration and Innovation, University of Idaho, Moscow, ID, United States; Department of Biological Sciences, University of Idaho, Moscow, ID, United States; Environmental Health Science & Research Bureau, Health Canada, Ottawa, ON, Canada; Department of Pediatrics, McMaster University, Hamilton, ON, Canada
推荐引用方式 GB/T 7714	Wang B.,Tsakiridis E.E.,Zhang S.,et al. The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue[J],2021,12(1).
APA	Wang B..,Tsakiridis E.E..,Zhang S..,Llanos A..,Desjardins E.M..,...&Steinberg G.R..(2021).The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue.Nature Communications,12(1).
MLA	Wang B.,et al."The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue".Nature Communications 12.1(2021).