近日，美国哈佛医学院Yu-Hua Tseng及其研究团队揭示，12-脂氧合酶通过从褐色脂肪中产生Omega-3脂类12-HEPE来调节寒冷适应和葡萄糖代谢。2019年10月出版的《细胞—代谢》发表了这项成果。

由于脂氧合酶（LOX）家族在冷适应中的作用仍然难以捉摸，因此研究人员希望了解LOX活性是否需要以及如何用于寒冷适应，并确定LOX产生的脂质产物，可以作为具有治疗潜力的寒冷模拟物对抗糖尿病。

通过在小鼠和人类中利用基于质谱的脂质组学，研究人员证明了寒冷刺激和β3-肾上腺素刺激可以促进棕色脂肪组织的12-LOX代谢产物的生物合成和释放。此外，小鼠棕色脂肪细胞中的12-LOX敲除损害了葡萄糖的摄取和代谢，导致体内对寒冷的适应能力减弱。

研究人员发现寒冷诱导的12-LOX产物12-HEPE是一种通过改善胰岛素样细胞内信号传导途径，促进葡萄糖吸收进入脂肪细胞和骨骼肌而改善葡萄糖代谢的棕色脂肪因子。

据介绍，不同的加氧酶及其脂蛋白产物已被证明通过介导维持体温所需的生理适应性参与产热作用。

附：英文原文

Title: 12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat

Author: Luiz Osório Leiria, Chih-Hao Wang, Matthew D. Lynes, Kunyan Yang, Farnaz Shamsi, Mari Sato, Satoru Sugimoto, Emily Y. Chen, Valerie Bussberg, Niven R. Narain, Brian E. Sansbury, Justin Darcy, Tian Lian Huang, Sean D. Kodani, Masaji Sakaguchi, Andréa L. Rocha, Tim J. Schulz, Alexander Bartelt, Gkhan S. Hotamisligil, Michael F. Hirshman, Klaus van Leyen, Laurie J. Goodyear, Matthias Blüher, Aaron M. Cypess, Michael A. Kiebish, Matthew Spite, Yu-Hua Tseng

Issue&Volume: VOLUME 30, ISSUE 4

Abstract: 

Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain body temperature. Since the role of the lipoxygenase (LOX) family in cold adaptation remains elusive, we aimed to investigate whether, and how, LOX activity is required for cold adaptation and to identify LOX-derived lipid mediators that could serve as putative cold mimetics with therapeutic potential to combat diabetes. By utilizing mass-spectrometry-based lipidomics in mice and humans, we demonstrated that cold and β3-adrenergic stimulation could promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue (BAT). Moreover, 12-LOX ablation in mouse brown adipocytes impaired glucose uptake and metabolism, resulting in blunted adaptation to the cold in vivo. The cold-induced 12-LOX product 12-HEPE was found to be a batokine that improves glucose metabolism by promoting glucose uptake into adipocytes and skeletal muscle through activation of an insulin-like intracellular signaling pathway.

DOI: 10.1016/j.cmet.2019.07.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30374-2