van Beek Lianne, van Klinken Jan B, Pronk Amanda C M, van Dam Andrea D, Dirven Eline, Rensen Patrick C N, Koning Frits, Willems van Dijk Ko, van Harmelen Vanessa
Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, PO Box 9600, 2300 RC, Leiden, the Netherlands.
Diabetologia. 2015 Jul;58(7):1601-9. doi: 10.1007/s00125-015-3594-8. Epub 2015 May 12.
AIMS/HYPOTHESIS: White adipose tissue (WAT) consists of various depots with different adipocyte functionality and immune cell composition. Knowledge of WAT-depot-specific differences in expandability and immune cell influx during the development of obesity is limited, therefore we aimed to characterise different WAT depots during the development of obesity in mice.
Gonadal WAT (gWAT), subcutaneous WAT (sWAT) and mesenteric WAT (mWAT) were isolated from male C57Bl/6J mice with different body weights (approximately 25-60 g) and analysed. Linear and non-linear regression models were used to describe the extent of WAT depot expandability and immune cell composition as a function of body weight.
Whereas mouse sWAT and mWAT continued to expand with body weight, gWAT expanded mainly during the initial phase of body weight gain. The expansion diminished after the mice reached a body weight of around 40 g. From this point on, gWAT crown-like structure formation, liver steatosis and insulin resistance occurred. Mouse WAT depots showed major differences in immune cell composition: gWAT consisted mainly of macrophages, whereas sWAT and mWAT primarily contained lymphocytes.
CONCLUSIONS/INTERPRETATION: Marked inter-depot differences exist in WAT immune cell composition and expandability. The limited storage capacity of gWAT seems to direct the development of metabolic disorders in male C57Bl/6J mice.
目的/假设:白色脂肪组织(WAT)由具有不同脂肪细胞功能和免疫细胞组成的多个储存库构成。关于肥胖发展过程中WAT储存库在可扩展性和免疫细胞流入方面的特异性差异的了解有限,因此我们旨在对小鼠肥胖发展过程中的不同WAT储存库进行特征描述。
从不同体重(约25 - 60克)的雄性C57Bl/6J小鼠中分离出性腺WAT(gWAT)、皮下WAT(sWAT)和肠系膜WAT(mWAT)并进行分析。使用线性和非线性回归模型来描述WAT储存库的可扩展性程度和免疫细胞组成随体重的变化情况。
小鼠的sWAT和mWAT随体重持续增长,而gWAT主要在体重增加的初始阶段扩张。小鼠体重达到约40克后,这种扩张减弱。从这一点开始,gWAT出现冠状结构形成、肝脏脂肪变性和胰岛素抵抗。小鼠WAT储存库在免疫细胞组成上存在主要差异:gWAT主要由巨噬细胞组成,而sWAT和mWAT主要含有淋巴细胞。
结论/解读:WAT免疫细胞组成和可扩展性存在明显的储存库间差异。gWAT有限的储存能力似乎主导了雄性C57Bl/6J小鼠代谢紊乱的发展。