Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation

Satoru Sugimoto; Hebe Agustina Mena; Brian E. Sansbury; Shio Kobayashi; Tadataka Tsuji; Chih Hao Wang; Xuanzhi Yin; Tian Lian Huang; Joji Kusuyama; Sean D. Kodani; Justin Darcy; Gerson Profeta; Nayara Pereira; Rudolph E. Tanzi; Can Zhang; Thomas Serwold; Efi Kokkotou; Laurie J. Goodyear; Aaron M. Cypess; Luiz Osório Leiria; Matthew Spite; Yu Hua Tseng

doi:10.1038/s42255-022-00590-0

Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation

Satoru Sugimoto, Hebe Agustina Mena, Brian E. Sansbury, Shio Kobayashi, Tadataka Tsuji, Chih Hao Wang, Xuanzhi Yin, Tian Lian Huang, Joji Kusuyama, Sean D. Kodani, Justin Darcy, Gerson Profeta, Nayara Pereira, Rudolph E. Tanzi, Can Zhang, Thomas Serwold, Efi Kokkotou, Laurie J. Goodyear, Aaron M. Cypess, Luiz Osório LeiriaMatthew Spite, Yu Hua Tseng

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	775-790
Number of pages	16
Journal	Nature Metabolism
Volume	4
Issue number	6
DOIs	https://doi.org/10.1038/s42255-022-00590-0
Publication status	Published - 2022 Jun
Externally published	Yes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Physiology (medical)
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s42255-022-00590-0

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Sugimoto, S., Mena, H. A., Sansbury, B. E., Kobayashi, S., Tsuji, T., Wang, C. H., Yin, X., Huang, T. L., Kusuyama, J., Kodani, S. D., Darcy, J., Profeta, G., Pereira, N., Tanzi, R. E., Zhang, C., Serwold, T., Kokkotou, E., Goodyear, L. J., Cypess, A. M., ... Tseng, Y. H. (2022). Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation. Nature Metabolism, 4(6), 775-790. https://doi.org/10.1038/s42255-022-00590-0

Sugimoto, S, Mena, HA, Sansbury, BE, Kobayashi, S, Tsuji, T, Wang, CH, Yin, X, Huang, TL, Kusuyama, J, Kodani, SD, Darcy, J, Profeta, G, Pereira, N, Tanzi, RE, Zhang, C, Serwold, T, Kokkotou, E, Goodyear, LJ, Cypess, AM, Leiria, LO, Spite, M & Tseng, YH 2022, 'Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation', Nature Metabolism, vol. 4, no. 6, pp. 775-790. https://doi.org/10.1038/s42255-022-00590-0

@article{4d9d02ba39a34a608ed635519001dd6b,

title = "Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation",

abstract = "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.",

author = "Satoru Sugimoto and Mena, {Hebe Agustina} and Sansbury, {Brian E.} and Shio Kobayashi and Tadataka Tsuji and Wang, {Chih Hao} and Xuanzhi Yin and Huang, {Tian Lian} and Joji Kusuyama and Kodani, {Sean D.} and Justin Darcy and Gerson Profeta and Nayara Pereira and Tanzi, {Rudolph E.} and Can Zhang and Thomas Serwold and Efi Kokkotou and Goodyear, {Laurie J.} and Cypess, {Aaron M.} and Leiria, {Luiz Os{\'o}rio} and Matthew Spite and Tseng, {Yu Hua}",

note = "Funding Information: This work was supported in part by US National Institutes of Health grants R01DK122808 (to Y.-H.T. and M.S.), R01DK077097 and R01DK102898 (to Y.-H.T.), R01HL106173 (to M.S.), R01DK099511 and R01DK112283 (to L.J.G.), P30DK036836 (to Joslin Diabetes Center{\textquoteright}s Diabetes Research Center) and by US Army Medical Research grant W81XWH-17-1-0428 (to Y.-H.T.). S.S. was supported by the Manpei Suzuki Diabetes Foundation in Japan. G.P. was supported by grant 2019/20554-7 from The Sao Paulo Research Foundation, Sao Paulo Research Foundation. L.O.L. was supported by an American Diabetes Association post-doctoral fellowship (1-16-PDF-063) and by the Sao Paulo Research Foundation grants 2017/02684 and 2019/26008-4. We thank M. Lynes, F. Shamsi and Y. Zhang for providing general technical support and helpful advice. We thank S. Dong for helping with animal work and A. Clermont, A. Dean and M. Halpin of the Joslin Diabetes Research Center Animal Physiology core for assisting with the studies using the diurnal incubators. We thank H. Takahashi for providing helpful advice related to the clinical aspects of this work. We thank the laboratory of B. Hammock for providing the sEH antibody. All the schematics of the experimental design were created with BioRender.com. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2022",

month = jun,

doi = "10.1038/s42255-022-00590-0",

language = "English",

volume = "4",

pages = "775--790",

journal = "Nature Metabolism",

issn = "2522-5812",

publisher = "Springer Berlin",

number = "6",

}

TY - JOUR

T1 - Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation

AU - Sugimoto, Satoru

AU - Mena, Hebe Agustina

AU - Sansbury, Brian E.

AU - Kobayashi, Shio

AU - Tsuji, Tadataka

AU - Wang, Chih Hao

AU - Yin, Xuanzhi

AU - Huang, Tian Lian

AU - Kusuyama, Joji

AU - Kodani, Sean D.

AU - Darcy, Justin

AU - Profeta, Gerson

AU - Pereira, Nayara

AU - Tanzi, Rudolph E.

AU - Zhang, Can

AU - Serwold, Thomas

AU - Kokkotou, Efi

AU - Goodyear, Laurie J.

AU - Cypess, Aaron M.

AU - Leiria, Luiz Osório

AU - Spite, Matthew

AU - Tseng, Yu Hua

N1 - Funding Information: This work was supported in part by US National Institutes of Health grants R01DK122808 (to Y.-H.T. and M.S.), R01DK077097 and R01DK102898 (to Y.-H.T.), R01HL106173 (to M.S.), R01DK099511 and R01DK112283 (to L.J.G.), P30DK036836 (to Joslin Diabetes Center’s Diabetes Research Center) and by US Army Medical Research grant W81XWH-17-1-0428 (to Y.-H.T.). S.S. was supported by the Manpei Suzuki Diabetes Foundation in Japan. G.P. was supported by grant 2019/20554-7 from The Sao Paulo Research Foundation, Sao Paulo Research Foundation. L.O.L. was supported by an American Diabetes Association post-doctoral fellowship (1-16-PDF-063) and by the Sao Paulo Research Foundation grants 2017/02684 and 2019/26008-4. We thank M. Lynes, F. Shamsi and Y. Zhang for providing general technical support and helpful advice. We thank S. Dong for helping with animal work and A. Clermont, A. Dean and M. Halpin of the Joslin Diabetes Research Center Animal Physiology core for assisting with the studies using the diurnal incubators. We thank H. Takahashi for providing helpful advice related to the clinical aspects of this work. We thank the laboratory of B. Hammock for providing the sEH antibody. All the schematics of the experimental design were created with BioRender.com. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

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U2 - 10.1038/s42255-022-00590-0

DO - 10.1038/s42255-022-00590-0

M3 - Article

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AN - SCOPUS:85132960749

SN - 2522-5812

VL - 4

SP - 775

EP - 790

JO - Nature Metabolism

JF - Nature Metabolism

IS - 6

ER -

Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation

Abstract

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