Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
Cell Rep. 2020 Jan 28;30(4):949-958.e6. doi: 10.1016/j.celrep.2019.12.089.
Under caloric restriction, bone marrow adipocytes (BM-Ads) do not decrease in size compared to white adipocytes, suggesting they harbor unique metabolic properties. We compare human primary BM-Ads with paired subcutaneous adipocytes (SC-Ads) using proteomic and lipidomic approaches. We find that, although SC-Ads and BM-Ads share similar morphological features, they possess distinct lipid metabolism. Although BM-Ad shows enrichment in proteins involved in cholesterol metabolism, correlating with increased free cholesterol content, proteins involved in lipolysis were downregulated. In particular, monoacylglycerol lipase expression is strongly reduced in BM-Ads, leading to monoacylglycerol accumulation. Consequently, basal and induced lipolytic responses are absent in BM-Ads, affirming their differences in metabolic fitness upon caloric restriction. These specific metabolic features are not recapitulated in vitro using common protocols to differentiate bone marrow mesenchymal stem cells. Thus, contrary to classical SC-Ads, BM-Ads display a specific lipid metabolism, as they are devoid of lipolytic activity and exhibit a cholesterol-orientated metabolism.
在热量限制下,骨髓脂肪细胞(BM-Ads)的大小与白色脂肪细胞相比并没有减小,这表明它们具有独特的代谢特性。我们使用蛋白质组学和脂质组学方法比较了人类原代 BM-Ads 与配对的皮下脂肪细胞(SC-Ads)。我们发现,尽管 SC-Ads 和 BM-Ads 具有相似的形态特征,但它们具有不同的脂质代谢。尽管 BM-Ad 显示出胆固醇代谢相关蛋白的富集,与游离胆固醇含量增加相关,但参与脂肪分解的蛋白被下调。特别是,单酰基甘油脂肪酶的表达在 BM-Ads 中强烈降低,导致单酰基甘油积累。因此,BM-Ads 中不存在基础和诱导性的脂肪分解反应,证实了它们在热量限制下代谢适应性的差异。在使用常见的分化骨髓间充质干细胞的方案进行体外实验时,并没有重现这些特定的代谢特征。因此,与经典的 SC-Ads 不同,BM-Ads 表现出特定的脂质代谢,因为它们缺乏脂肪分解活性,并表现出胆固醇导向的代谢。