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

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

• Document type: Journal article
• Source: NATURE METABOLISM; v. 4, n. 6, p. 28-pg., 2022-06-01.

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 beta 3-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. Sugimoto et al. show that maresin 2, a specialized pro-resolving mediator that is secreted from brown adipose tissue upon cold exposure, contributes to amelioration of obesity-induced inflammation. (AU)

• FAPESP's process: 19/26008-4 - Adipocyte-secreted lipids as messengers linking insulin resistance to hyperinsulinemia in obesity
• Grantee: Luiz Osório Silveira Leiria
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/20554-7 - Investigation of mechanisms of miRNA biogenesis activation by the beta-adrenergic pathway
• Grantee: Gerson Profeta de Souza
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate