Khan Salmaan Ahmed, Wollaston-Hayden Edith E, Markowski Todd W, Higgins LeeAnn, Mashek Douglas G
Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108.
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455.
J Lipid Res. 2015 Dec;56(12):2260-72. doi: 10.1194/jlr.M056812. Epub 2015 Sep 28.
Hepatic steatosis is characterized by the accumulation of lipid droplets (LDs), which are composed of a neutral lipid core surrounded by a phospholipid monolayer embedded with many proteins. Although the LD-associated proteome has been investigated in multiple tissues and organisms, the dynamic changes in the murine LD-associated proteome in response to obesity and hepatic steatosis have not been studied. We characterized the hepatic LD-associated proteome of C57BL/6J male mouse livers following high-fat feeding using isobaric tagging for relative and absolute quantification. Of the 1,520 proteins identified with a 5% local false discovery rate, we report a total of 48 proteins that were increased and 52 proteins that were decreased on LDs in response to high-fat feeding. Most notably, ribosomal and endoplasmic reticulum proteins were increased and extracellular and cytosolic proteins were decreased in response to high-fat feeding. Additionally, many proteins involved in fatty acid catabolism or xenobiotic metabolism were enriched in the LD fraction following high-fat feeding. In contrast, proteins involved in glucose metabolism and liver X receptor or retinoid X receptor activation were decreased on LDs of high-fat-fed mice. This study provides insights into unique biological functions of hepatic LDs under normal and steatotic conditions.
肝脂肪变性的特征是脂滴（LDs）的积累，脂滴由中性脂质核心组成，周围是嵌入许多蛋白质的磷脂单层。尽管已经在多种组织和生物体中研究了与脂滴相关的蛋白质组，但尚未研究小鼠中与脂滴相关的蛋白质组在肥胖和肝脂肪变性反应中的动态变化。我们使用相对和绝对定量的等压标记法，对高脂喂养后C57BL/6J雄性小鼠肝脏中与肝脂滴相关的蛋白质组进行了表征。在以5%的局部错误发现率鉴定出的1520种蛋白质中，我们报告了总共48种在高脂喂养后脂滴上增加的蛋白质和52种减少的蛋白质。最值得注意的是，核糖体蛋白和内质网蛋白增加，而细胞外蛋白和胞质蛋白在高脂喂养后减少。此外，许多参与脂肪酸分解代谢或异生物质代谢的蛋白质在高脂喂养后在脂滴部分中富集。相反，参与葡萄糖代谢以及肝脏X受体或视黄醇X受体激活的蛋白质在高脂喂养小鼠的脂滴上减少。这项研究为正常和脂肪变性条件下肝脂滴的独特生物学功能提供了见解。
