Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA 95616, USA.
J Nutr. 2011 Jun;141(6):1172-80. doi: 10.3945/jn.110.127068. Epub 2011 Apr 20.
In severe obesity, white adipose tissue (WAT) inflammation and macrophage infiltration are thought to contribute to WAT and whole-body insulin resistance. Specific players involved in triggering and maintaining inflammation (i.e. those regulating adipokine release and WAT macrophage recruitment, retention, or function) remain to be fully elaborated, and the degree to which moderate obesity promotes WAT inflammation remains to be clarified further. Therefore, we characterized adiposity and metabolic phenotypes in adult male C57BL/6J mice fed differing levels of dietary fat (10, 45, and 60% of energy) for 12 wk, concurrent with determinations of WAT inflammation markers and mRNA expression of leukocyte-derived integrins (CD11b, CD11c, CD11d) involved in macrophage extravasation and tissue macrophage homing/retention. As expected, a lard-based, very high-fat diet (60% energy) significantly increased adiposity and glucose intolerance compared with 10% fat-fed controls, coincident with higher retroperitoneal (RP) WAT transcript levels for proinflammatory factors and macrophage markers, including TNFα and CD68 mRNA, which were ~3- and ~15-fold of control levels, respectively (P < 0.001). Mice fed the 45% fat diet had more moderate obesity, less glucose intolerance, and lower WAT macrophage/inflammatory marker mRNA abundances compared with 60% fat-fed mice; TNFα and CD68 mRNA levels were ~2- and ~5-fold of control levels (P < 0.01). Relative WAT expression of CD11d was massively induced by obesity to an extent greater than any other inflammatory marker (to >300-fold of controls in the 45 and 60% fat groups) (P < 0.0001) and this induction was WAT specific. Because we found that CD11d expression also increased in RP-WAT of Zucker obese rats and in the subcutaneous WAT of obese adult women, this appears to be a common feature of obesity. Observed correlations of WAT macrophage transcript marker abundances with body weight in lean to modestly obese mice raises an interesting possibility that the activities of at least some WAT macrophages are closely linked to the normal adipose remodeling that is a requisite for changes in WAT energy storage capacity.
在严重肥胖的情况下，人们认为白色脂肪组织 (WAT) 的炎症和巨噬细胞浸润是导致 WAT 和全身胰岛素抵抗的原因。触发和维持炎症的特定参与者（即调节脂肪因子释放和 WAT 巨噬细胞募集、保留或功能的那些）仍有待充分阐述，中度肥胖促进 WAT 炎症的程度仍有待进一步澄清。因此，我们描述了在喂食不同水平的膳食脂肪（10%、45%和 60%的能量）的成年雄性 C57BL/6J 小鼠中脂肪量和代谢表型，同时测定 WAT 炎症标志物和参与巨噬细胞渗出和组织巨噬细胞归巢/保留的白细胞衍生整合素（CD11b、CD11c、CD11d）的 mRNA 表达。正如预期的那样，基于猪油的极高脂肪饮食（60%的能量）与 10%脂肪喂养的对照组相比，显著增加了肥胖和葡萄糖不耐受，同时腹膜后 (RP) WAT 促炎因子和巨噬细胞标志物（包括 TNFα 和 CD68 mRNA）的转录水平升高，分别为对照水平的 3- 和 15 倍（P < 0.001）。与 60%脂肪喂养的小鼠相比，喂食 45%脂肪饮食的小鼠体重更适中，葡萄糖不耐受程度更低，WAT 巨噬细胞/炎症标志物 mRNA 丰度更低；TNFα 和 CD68 mRNA 水平分别为对照水平的 2- 和 5 倍（P < 0.01）。与其他炎症标志物相比，CD11d 的相对 WAT 表达被肥胖强烈诱导（在 45%和 60%脂肪组中>300 倍于对照）（P < 0.0001），这种诱导是 WAT 特异性的。因为我们发现 CD11d 表达在 Zucker 肥胖大鼠的腹膜后 WAT 和肥胖成年女性的皮下 WAT 中也增加，所以这似乎是肥胖的一个共同特征。在从瘦到适度肥胖的小鼠中，WAT 巨噬细胞转录标志物丰度与体重的观察相关性提出了一个有趣的可能性，即至少一些 WAT 巨噬细胞的活性与 WAT 能量储存能力变化所需的正常脂肪重塑密切相关。
