Sadler Dawn, Mattacks Christine A, Pond Caroline M
Department of Biological Sciences, The Open University, Milton Keynes, UK.
J Anat. 2005 Dec;207(6):769-81. doi: 10.1111/j.1469-7580.2005.00506.x.
The time course and cellular basis for inflammation-induced hypertrophy of adipose tissue were investigated over 20 weeks in mature male rats. Mild inflammation was induced by subcutaneous injection of 20 microg lipopolysaccharide into one hind-leg three times/week for 4 or 8 weeks, followed by up to 12 weeks 'rest' without intervention. Mean volume and frequency of apoptosis (TUNEL assay) were measured in adipocytes isolated from sites defined by their anatomical relations to lymph nodes, plus numbers of CCL21-stimulated lymph node-derived and adipose tissue-derived dendritic cells. Experimental inflammation increased dendritic cells and adipocyte apoptosis in the locally stimulated popliteal depot and the lymphoid tissue-associated regions of the contralateral popliteal and mesentery and omentum. Responses declined slowly after inflammation ended, but all measurements from the locally stimulated popliteal depot, and the omentum, were still significantly different from controls after 12 weeks rest. The locally stimulated popliteal adipose tissue enlarged by 5% within 4 weeks and remained larger than the control. We conclude that prolonged inflammation induces permanent enlargement, greater adipocyte turnover and increased dendritic cell surveillance in the adjacent adipose tissue and the omentum. The experiment suggests a mechanism for selective hypertrophy of lymphoid tissue-associated adipose tissue in chronic stress and inflammatory disorders, including impaired lymph drainage, Crohn's disease and HIV-associated lipodystrophy, and a link between evolutionary fitness, sexual selection and aesthetically pleasing body symmetry. It would be useful for further study of molecular mechanisms in inflammation-induced local hypertrophy of adipose tissue and development of specific therapies that avoid interference with whole-body lipid metabolism.
在成熟雄性大鼠中，对炎症诱导的脂肪组织肥大的时间进程和细胞基础进行了为期20周的研究。通过每周三次向一条后腿皮下注射20微克脂多糖，持续4周或8周来诱导轻度炎症，随后进行长达12周的无干预“休息”。对从根据其与淋巴结的解剖关系确定的部位分离出的脂肪细胞进行平均体积和凋亡频率（TUNEL检测）测量，同时测量CCL21刺激的淋巴结来源和脂肪组织来源的树突状细胞数量。实验性炎症增加了局部刺激的腘窝脂肪库以及对侧腘窝、肠系膜和网膜的淋巴组织相关区域中的树突状细胞和脂肪细胞凋亡。炎症结束后反应缓慢下降，但在休息12周后，来自局部刺激的腘窝脂肪库和网膜的所有测量值仍与对照组有显著差异。局部刺激的腘窝脂肪组织在4周内增大了5%，并且仍然大于对照组。我们得出结论，长期炎症会导致永久性增大、更高的脂肪细胞更新率以及相邻脂肪组织和网膜中树突状细胞监测增加。该实验提示了慢性应激和炎症性疾病（包括淋巴引流受损、克罗恩病和HIV相关脂肪营养不良）中淋巴组织相关脂肪组织选择性肥大的机制，以及进化适应性、性选择和美观的身体对称性之间的联系。这对于进一步研究炎症诱导的脂肪组织局部肥大的分子机制以及开发避免干扰全身脂质代谢的特异性疗法将是有用的。
