biostudies-literatureSugimoto SNIDDK NIH HHSNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases775-790https://www.ebi.ac.uk/biostudies/studies/S-EPMC9792164biostudies-literatureUnknown4(6)Obesity induces chronic inflammation resulting in insulin resistance and metabolic disorders. Cold exposure can improve insulin sensitivity in humans and rodents, but the mechanisms have not been fully elucidated. Here, we find that cold resolves obesity-induced inflammation and insulin resistance and improves glucose tolerance in diet-induced obese mice. The beneficial effects of cold exposure on improving obesity-induced inflammation and insulin resistance depend on brown adipose tissue (BAT) and liver. Using targeted liquid chromatography with tandem mass spectrometry, we discovered that cold and β3-adrenergic stimulation promote BAT to produce maresin 2 (MaR2), a member of the specialized pro-resolving mediators of bioactive lipids that play a role in the resolution of inflammation. Notably, MaR2 reduces inflammation in obesity in part by targeting macrophages in the liver. Thus, BAT-derived MaR2 could contribute to the beneficial effects of BAT activation in resolving obesity-induced inflammation and may inform therapeutic approaches to combat obesity and its complications.Nature metabolismBrown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation.PMC9792164R01 DK112283R01DK102898R01 DK077097R01HL106173R01 HL106173R01DK122808R01DK077097R01DK099511R01 DK099511P30 DK036836R01 DK102898R01 DK122808R01DK112283Yin XTsuji TWang CHSugimoto SSansbury BEKobayashi SPereira NSerwold TSpite MProfeta GCypess AMDarcy JTseng YHKodani SDTanzi REGoodyear LJHuang TLLeiria LOZhang CMena HAKusuyama JKokkotou EfalseBrown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation.Obesity induces chronic inflammation resulting in insulin resistance and metabolic disorders. Cold exposure can improve insulin sensitivity in humans and rodents, but the mechanisms have not been fully elucidated. Here, we find that cold resolves obesity-induced inflammation and insulin resistance and improves glucose tolerance in diet-induced obese mice. The beneficial effects of cold exposure on improving obesity-induced inflammation and insulin resistance depend on brown adipose tissue (BAT) and liver. Using targeted liquid chromatography with tandem mass spectrometry, we discovered that cold and β3-adrenergic stimulation promote BAT to produce maresin 2 (MaR2), a member of the specialized pro-resolving mediators of bioactive lipids that play a role in the resolution of inflammation. Notably, MaR2 reduces inflammation in obesity in part by targeting macrophages in the liver. Thus, BAT-derived MaR2 could contribute to the beneficial effects of BAT activation in resolving obesity-induced inflammation and may inform therapeutic approaches to combat obesity and its complications.2022-01-01T00:00:00Z2022 Jun2025-04-04T12:10:23.848Z2025-02-19T04:43:04.215ZS-EPMC97921643576087210.1038/s42255-022-00590-0