Johnson P R, Stern J S, Horwitz B A, Harris R E, Greene S F
Department of Nutrition, University of California at Davis 95616, USA.
Am J Clin Nutr. 1997 Oct;66(4):890-903. doi: 10.1093/ajcn/66.4.890.
Zucker obese (fa/fa) and lean (Fa/Fa) rats were fed a soy protein diet ad libitum under barrier conditions from 4 wk of age until death. Obese rats were also pair fed with lean controls to prevent hyperphagia. Time of death was determined and tissues collected at necropsy for histologic examination. Lean rats had longer 10th percentile survivorship (males 966 compared with 667 d, females 983 compared with 620 d) and maximum life spans (males 1067 compared with 803 d, females 1163 compared with 744 d) than did obese rats. Preventing hyperphagia increased maximum life span in both males (1010 d) and females (975 d). Pathologies in lean rats were similar to those reported for other rodent strains. For obese rats fed ad libitum, end-stage renal disease (ESRD) was the major cause of mortality (males: 91.1%, females: 93.3%). Prevention of hyperphagia decreased deaths attributable to ESRD (males: 64.4%, females: 51.1%). A smaller restriction in energy intake (8-18%) required to prevent hyperphagia compared with the 35-40% in most other studies produced similar increases in longevity, suggesting that obese Zucker rats are particularly sensitive to energy restriction. Amelioration of early onset of renal disease is a likely explanation. Percentage body fat in food-restricted obese rats did not differ from that of animals fed ad libitum; thus, reduced longevity is not the result of obesity per se, but rather is influenced by other metabolic pathologies occurring in this strain of rats homozygous for the fa gene. Because microalbuminuria with progression to ESRD is a complication in human obesity, the Zucker strain offers the opportunity to investigate initiating mechanisms of this pathology.
从4周龄起直至死亡，将Zucker肥胖（fa/fa）大鼠和瘦型（Fa/Fa）大鼠置于屏障环境中，随意喂食大豆蛋白饮食。肥胖大鼠还与瘦型对照大鼠进行配对喂食，以防止过度摄食。确定死亡时间，并在尸检时收集组织进行组织学检查。与肥胖大鼠相比，瘦型大鼠的第10百分位数生存期更长（雄性：966天对667天，雌性：983天对620天），最大寿命也更长（雄性：1067天对803天，雌性：1163天对744天）。防止过度摄食可增加雄性（1010天）和雌性（975天）的最大寿命。瘦型大鼠的病理学表现与其他啮齿动物品系报道的相似。对于随意喂食的肥胖大鼠，终末期肾病（ESRD）是主要死亡原因（雄性：91.1%，雌性：93.3%）。防止过度摄食可降低ESRD导致的死亡（雄性：64.4%，雌性：51.1%）。与大多数其他研究中35 - 40%的能量摄入限制相比，防止过度摄食所需的较小能量摄入限制（8 - 18%）就能产生类似的寿命延长效果，这表明肥胖的Zucker大鼠对能量限制特别敏感。肾病早期发病的改善可能是一个解释。食物限制的肥胖大鼠的体脂百分比与随意喂食的动物没有差异；因此，寿命缩短不是肥胖本身的结果，而是受该fa基因纯合大鼠品系中发生的其他代谢病理学影响。由于微量白蛋白尿进展为ESRD是人类肥胖的一种并发症，Zucker品系为研究这种病理学的起始机制提供了机会。
