The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue.
AMP-Activated Protein Kinase Kinases
Adipose Tissue, Brown
/ physiopathology
Animals
Chlorpyrifos
/ metabolism
Cyclic AMP
/ metabolism
Energy Metabolism
Food Contamination
/ analysis
Humans
Male
Mice
Mice, Inbred C57BL
Obesity
/ chemically induced
Pesticides
/ metabolism
Protein Kinases
/ genetics
Thermogenesis
/ drug effects
Uncoupling Protein 1
/ genetics
p38 Mitogen-Activated Protein Kinases
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 08 2021
27 08 2021
Historique:
received:
11
08
2020
accepted:
02
08
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
2
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34453052
doi: 10.1038/s41467-021-25384-y
pii: 10.1038/s41467-021-25384-y
pmc: PMC8397754
doi:
Substances chimiques
Pesticides
0
Uncoupling Protein 1
0
Cyclic AMP
E0399OZS9N
Protein Kinases
EC 2.7.-
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
AMP-Activated Protein Kinase Kinases
EC 2.7.11.3
Chlorpyrifos
JCS58I644W
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5163Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM104420
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103324
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125281
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125283
Pays : United States
Informations de copyright
© 2021. The Author(s).
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