Lin X, Chavez M R, Bruch R C, Kilroy G E, Simmons L A, Lin L, Braymer H D, Bray G A, York D A
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
J Nutr. 1998 Oct;128(10):1606-13. doi: 10.1093/jn/128.10.1606.
Osborne-Mendel (OM) and S5B/Pl rats differ in their sensitivity to develop obesity when fed a high fat (HF) diet; OM rats become obese, whereas S5B/Pl rats remain thin. We have investigated the possibilities that either an impaired leptin response or resistance to leptin action underlies the sensitivity to this form of obesity in OM rats. In Experiment 1, OM and S5B/Pl rats fed a nonpurified diet were killed at d 0 or were fed either a HF (56% fat energy) or a low fat (LF, 10% fat energy) diet for 2 or 7 d. The HF diet increased serum leptin significantly by d 2 to levels that were similar in both rat strains. At 7 d, leptin levels were lower than at d 2 but remained higher than levels in the d 0 control groups. The leptin mRNA:18S RNA ratio in epididymal adipose tissue increased to higher levels in HF-fed OM rats than in S5B/Pl rats fed that diet. However, although the LF diet had no effect in S5B/Pl rats, it increased leptin mRNA levels in epididymal adipose tissue of OM rats compared with the controls fed the nonpurified diet. In Experiment 2, OM and S5B/Pl rats were fed HF or LF diets for 5 wk. At that time, their feeding response to a range of leptin doses (0, 1, 5 or 10 microgram) given intracerebroventricularly was tested after overnight food deprivation. There was a similar dose-dependent reduction in energy intake in response to leptin in both OM and S5B/Pl rats. These responses were independent of the diet. The data suggest that the susceptibility of OM rats to HF diet-induced obesity is not related to either a loss of central sensitivity to leptin or a failure to enhance leptin production acutely, although the failure to maintain chronically increased levels of serum leptin could contribute to the obesity.
奥斯本-孟德尔（OM）大鼠和S5B/Pl大鼠在喂食高脂（HF）饮食时，发生肥胖的敏感性存在差异；OM大鼠会肥胖，而S5B/Pl大鼠则保持消瘦。我们研究了OM大鼠对这种形式的肥胖敏感性的潜在原因，即瘦素反应受损或对瘦素作用产生抵抗。在实验1中，喂食非纯化饮食的OM和S5B/Pl大鼠在第0天被处死，或者喂食HF（56%脂肪能量）或低脂（LF，10%脂肪能量）饮食2天或7天。到第2天，HF饮食使血清瘦素显著升高，两种大鼠品系的血清瘦素水平相似。在第7天，瘦素水平低于第2天，但仍高于第0天对照组的水平。与喂食该饮食的S5B/Pl大鼠相比，喂食HF的OM大鼠附睾脂肪组织中的瘦素mRNA:18S RNA比值升高到更高水平。然而，尽管LF饮食对S5B/Pl大鼠没有影响，但与喂食非纯化饮食的对照组相比，它增加了OM大鼠附睾脂肪组织中的瘦素mRNA水平。在实验2中，OM和S5B/Pl大鼠喂食HF或LF饮食5周。那时，在过夜禁食后，测试它们对一系列脑室内注射的瘦素剂量（0、1、5或10微克）的进食反应。OM和S5B/Pl大鼠对瘦素的反应均有类似的剂量依赖性能量摄入减少。这些反应与饮食无关。数据表明，OM大鼠对HF饮食诱导的肥胖的易感性既不与对瘦素的中枢敏感性丧失有关，也不与急性瘦素产生增强失败有关，尽管血清瘦素水平未能长期维持升高可能导致肥胖。
