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.

肥胖会诱发慢性炎症，导致胰岛素抵抗和代谢紊乱。寒冷暴露可以提高人类和啮齿动物的胰岛素敏感性，但其机制尚未完全阐明。在这里，我们发现寒冷解决了肥胖引起的炎症和胰岛素抵抗，并改善了饮食引起的肥胖小鼠的葡萄糖耐量。寒冷暴露对改善肥胖引起的炎症和胰岛素抵抗的有益作用取决于棕色脂肪组织 (BAT) 和肝脏。使用靶向液相色谱和串联质谱法，我们发现冷刺激和 β3-肾上腺素能刺激促进 BAT 产生 maresin 2 (MaR2)，这是一种在炎症消退中发挥作用的生物活性脂质的特殊促分解介质。尤其，MaR2 部分通过靶向肝脏中的巨噬细胞来减少肥胖引起的炎症。因此，BAT 衍生的 MaR2 可能有助于 BAT 激活在解决肥胖引起的炎症方面的有益作用，并可能为对抗肥胖及其并发症的治疗方法提供信息。