德国汉堡大学埃彭多夫医学中心Joerg Heeren研究组宣布他们发现内皮细胞溶酶体脂蛋白加工途径介导了脂肪组织的热适应性。该研究成果于2020年12月22日在线发表在国际学术期刊《细胞-代谢》杂志上。

在本研究中，研究人员表明在小鼠遇冷刺激后，脂肪组织中的血管内皮细胞会内吞大量完整的富含甘油三酯的脂蛋白（TRL）颗粒。这些脂蛋白随后通过内体-溶酶体途径，并在溶酶体中被酸性脂肪酶（LAL）加工。内皮细胞特异性LAL缺失会导致褐色和棕色/米色脂肪细胞招募减少，从而导致产热能力受损。从机制上讲，内皮细胞和脂肪细胞前体LAL诱导的TRL加工通过β-氧化产生活性氧，其反过来刺激缺氧诱导因子1α依赖的增殖反应。总而言之，这项研究证明了TRL颗粒被棕色脂肪组织（BAT）和白色脂肪组织（WAT）吸收的生理作用，并揭示了内皮细胞脂蛋白加工途径是热适应过程中脂肪组织重塑的重要决定因素。

据介绍，为了应对冷刺激，毛细血管腔内BAT和WAT中脂蛋白脂肪酶介导的TRL水解后，产热脂肪细胞将内吞大量脂肪酸。

附：英文原文

Title: Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation

Author: Alexander W. Fischer, Michelle Y. Jaeckstein, Kristina Gottschling, Markus Heine, Frederike Sass, Nils Mangels, Christian Schlein, Anna Worthmann, Oliver T. Bruns, Yucheng Yuan, Hua Zhu, Ou Chen, Harald Ittrich, Stefan K. Nilsson, Patrik Stefanicka, Jozef Ukropec, Miroslav Balaz, Hua Dong, Wenfei Sun, Rudolf Reimer, Ludger Scheja, Joerg Heeren

Issue&Volume: 2020-12-22

Abstract: In response to cold exposure, thermogenic adipocytes internalize large amounts offatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins(TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue(WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adiposetissues endocytose substantial amounts of entire TRL particles. These lipoproteinssubsequently follow the endosomal-lysosomal pathway, where they undergo lysosomalacid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency resultsin impaired thermogenic capacity as a consequence of reduced recruitment of brownand brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferationof endothelial cells and adipocyte precursors via beta-oxidation-dependent productionof reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependentproliferative responses. In conclusion, this study demonstrates a physiological rolefor TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processingas an important determinant of adipose tissue remodeling during thermogenic adaptation.

DOI: 10.1016/j.cmet.2020.12.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30656-2