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

被引：0

作者：

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

机构：

[1] Joslin Diabetes Center,Section on Integrative Physiology and Metabolism, Research Division

[2] Harvard Medical School,Department of Anesthesiology, Perioperative and Pain Medicine

[3] Center for Experimental Therapeutics and Reperfusion Injury,Section of Immunobiology

[4] Brigham and Women’s Hospital and Harvard Medical School,Department of Pharmacology, Ribeirão Preto Medical School

[5] Research Division,Genetics and Aging Research Unit

[6] Joslin Diabetes Center,Department of Medicine, Division of Gastroenterology

[7] Harvard Medical School,Diabetes, Endocrinology, and Obesity Branch

[8] University of São Paulo,Harvard Stem Cell Institute

[9] McCance Center for Brain Health,undefined

[10] Department of Neurology,undefined

[11] Massachusetts General Hospital and Harvard Medical School,undefined

[12] Beth Israel Deaconess Medical Center,undefined

[13] Harvard Medical School,undefined

[14] Intramural Research Program,undefined

[15] National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),undefined

[16] NIH,undefined

[17] Harvard University,undefined

来源：

Nature Metabolism | 2022年 / 4卷

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摘要：

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.

引用

页码：775 / 790

页数：15