Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice
Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice
复制标题
DOI：
10.1007/s00418-011-0847-6
复制
发表时间：
2011-10-01
影响因子：
2.3
通讯作者：
Gotow, Takahiro
中科院分区：
文献类型：
--
作者：
Shiozaki, Motoko;Hayakawa, Naoya;Gotow, Takahiro
白藜芦醇已被广泛研究，因为它在延缓与年龄有关的疾病，从而延长寿命的有益效果，可能是模仿热量限制。在这项研究中，使用细胞生物学技术来研究白藜芦醇如何影响35至55周龄的加速衰老小鼠P10（SAMP10）中的肝细胞，特别强调线粒体和脂滴之间的关系。SAMP10的存活率、体重和摄食量在对照组和白藜芦醇治疗组之间没有显著差异。与对照组相比，经处理的肝脏发生了显著变化，如下所示。肝细胞中脂滴减少，线粒体数量增加。乙酰辅酶A羧化酶的磷酸化和线粒体ATP合成酶β亚基和锰超氧化物歧化酶（SOD 2）的表达增加。线粒体，表达更多的SOD 2，更紧密地与脂滴，这表明通过激活线粒体功能的脂解增强。组织蛋白酶D在肝细胞中表达较少，但在枯否细胞中表达增强，枯否细胞的数量和大小增加，具有更多的溶酶体相关特征。总之，白藜芦醇可以激活线粒体，导致消耗脂质，并且还可以激活枯否细胞，通过枯否细胞可以为肝细胞创造有益的环境。两者都可能与肝脏功能的改善有关，肝脏是代谢调节的核心器官。
Resveratrol has been extensively investigated because of its beneficial effects in delaying age-related diseases, thus extending the lifespan, possibly by mimicking calorie restriction. For this study, cell biological techniques were used to examine how resveratrol influenced hepatocytes in a senescence-accelerated mouse P10 (SAMP10), treated from 35 to 55 weeks of age, with special emphasis on the relationship between mitochondria and lipid droplets. Survival ratio, body weight and food intake of SAMP10 did not differ significantly between the control and resveratrol-treated groups. Compared with the control, the treated livers were altered significantly, as follows. Lipid droplets were reduced and mitochondria were increased in number in hepatocytes. Phosphorylation of acetyl-CoA carboxylase and the expression of both the mitochondrial ATP synthase beta subunit and Mn superoxide dismutase (SOD2) were increased. Mitochondria, expressing more SOD2, were more tightly associated with lipid droplets, suggesting the enhancement of lipolysis through the activation of mitochondrial functions. Cathepsin D expression was less in hepatocytes but enhanced in Kupffer cells, which were increased in number and size with more numerous lysosome-related profiles. Together, resveratrol may activate mitochondria resulting in consuming lipids, and may also activate Kupffer cells by which a beneficial milieu for hepatocytes may be created. Both might be related to improvement in the functioning of the liver, which is the organ that is central to metabolic regulation.