Lipid Laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden;
Am J Physiol Endocrinol Metab. 2014 Feb;306(3):E267-74. doi: 10.1152/ajpendo.00249.2013. Epub 2013 Dec 10.
Cancer cachexia is associated with pronounced adipose tissue loss due to, at least in part, increased fat cell lipolysis. MicroRNAs (miRNAs) have recently been implicated in controlling several aspects of adipocyte function. To gain insight into the possible impact of miRNAs on adipose lipolysis in cancer cachexia, global miRNA expression was explored in abdominal subcutaneous adipose tissue from gastrointestinal cancer patients with (n = 10) or without (n = 11) cachexia. Effects of miRNA overexpression or inhibition on lipolysis were determined in human in vitro differentiated adipocytes. Out of 116 miRNAs present in adipose tissue, five displayed distinct cachexia-associated expression according to both microarray and RT-qPCR. Four (miR-483-5p/-23a/-744/-99b) were downregulated, whereas one (miR-378) was significantly upregulated in cachexia. Adipose expression of miR-378 associated strongly and positively with catecholamine-stimulated lipolysis in adipocytes. This correlation is most probably causal because overexpression of miR-378 in human adipocytes increased catecholamine-stimulated lipolysis. In addition, inhibition of miR-378 expression attenuated stimulated lipolysis and reduced the expression of LIPE, PLIN1, and PNPLA2, a set of genes encoding key lipolytic regulators. Taken together, increased miR-378 expression could play an etiological role in cancer cachexia-associated adipose tissue loss via effects on adipocyte lipolysis.
癌症恶病质与明显的脂肪组织损失有关，至少部分原因是脂肪细胞脂解增加。microRNAs (miRNAs) 最近被认为在控制脂肪细胞功能的几个方面发挥作用。为了深入了解 miRNAs 对癌症恶病质中脂肪分解的可能影响，研究人员探索了胃肠道癌患者腹部皮下脂肪组织中的整体 miRNA 表达，这些患者中有（n=10）或没有（n=11）恶病质。通过体外分化的人类脂肪细胞确定 miRNA 过表达或抑制对脂肪分解的影响。在脂肪组织中存在的 116 种 miRNA 中，有 5 种根据微阵列和 RT-qPCR 显示出明显的恶病质相关表达。其中 4 种（miR-483-5p/-23a/-744/-99b）下调，而 1 种（miR-378）在恶病质中显著上调。脂肪组织中 miR-378 的表达与脂肪细胞中儿茶酚胺刺激的脂肪分解强烈且呈正相关。这种相关性很可能是因果关系，因为在人类脂肪细胞中过表达 miR-378 增加了儿茶酚胺刺激的脂肪分解。此外，抑制 miR-378 的表达减弱了刺激的脂肪分解，并降低了编码关键脂肪分解调节剂的基因 LIPE、PLIN1 和 PNPLA2 的表达。综上所述，miR-378 的表达增加可能通过对脂肪细胞脂肪分解的影响，在癌症恶病质相关脂肪组织损失中发挥病因作用。
