Morin C L, Eckel R H, Marcel T, Pagliassotti M J
University of Colorado Health Sciences Center, Department of Medicine, Denver 80262, USA.
Endocrinology. 1997 Nov;138(11):4665-71. doi: 10.1210/endo.138.11.5519.
Adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) has been associated with genetic models of insulin resistance and obesity. It is presently unknown if secreted AT-TNF protein is bioactive or whether it can be increased by environmentally induced obesity. In this study, male Wistar rats were fed either a low fat (LF; 12% of energy from corn oil) or a high fat (HF; 45% of energy from corn oil) diet for 5 weeks. From previous data, it is known that after 3 weeks, HF fed animals are obese and insulin resistant compared with the LF group. Hence, animals were killed at 1 week of HF feeding, during the acute response to the diet, and at 5 weeks, when differences in body fat are manifest. Weight gain was significantly increased by diet (P = 0.03) and time (P < 0.0001). AT-TNF bioactivity was measured on secreted protein collected from medium of minced, incubated epididymal (EPI), mesenteric (MES), and retroperitoneal (RETRO) fat pads. AT-TNF bioactivity was significantly increased by diet (P = 0.003) in the RETRO pad and tended to increase (P = 0.07) in EPI. AT-TNF activity was unaffected by diet or time in the MES pad. In the RETRO pad, TNF activity correlated negatively with RETRO fat cell number (r = -0.46, P = 0.002). Secreted AT-TNF protein did not correlate with AT-TNF activity but instead decreased in RETRO with time but not diet. In EPI, secreted AT-TNF protein decreased with the HF diet. Thus, these data suggest that high fat diets and obesity can influence AT-TNF bioactivity and secretion but in an apparent fat pad-specific manner.
脂肪组织来源的肿瘤坏死因子-α（AT-TNF）与胰岛素抵抗和肥胖的遗传模型有关。目前尚不清楚分泌的AT-TNF蛋白是否具有生物活性，或者它是否会因环境诱导的肥胖而增加。在本研究中，雄性Wistar大鼠分别喂食低脂（LF；12%的能量来自玉米油）或高脂（HF；45%的能量来自玉米油）饮食5周。根据先前的数据，已知在3周后，与LF组相比，喂食HF的动物肥胖且胰岛素抵抗。因此，在喂食HF 1周时（对饮食的急性反应期间）以及5周时（身体脂肪差异明显时）处死动物。饮食（P = 0.03）和时间（P < 0.0001）均显著增加体重。从切碎并孵育的附睾（EPI）、肠系膜（MES）和腹膜后（RETRO）脂肪垫的培养基中收集分泌蛋白，测定AT-TNF生物活性。RETRO脂肪垫中，饮食显著增加AT-TNF生物活性（P = 0.003），EPI中AT-TNF生物活性有增加趋势（P = 0.07）。MES脂肪垫中，AT-TNF活性不受饮食或时间影响。在RETRO脂肪垫中，TNF活性与RETRO脂肪细胞数量呈负相关（r = -0.46，P = 0.002）。分泌的AT-TNF蛋白与AT-TNF活性不相关，相反，RETRO脂肪垫中其随时间减少而非饮食减少。在EPI中，分泌的AT-TNF蛋白随HF饮食减少。因此，这些数据表明高脂饮食和肥胖可影响AT-TNF生物活性和分泌，但方式明显具有脂肪垫特异性。
