Heo Y-R, Claycombe K, Jones B H, Wright P, Truett G E, Zemel M, Banz W, Maher M, Moustaid-Moussa N
University of Tennessee, Department of Nutrition, Knoxville, TN 37996-1920, USA.
Horm Metab Res. 2002 Nov-Dec;34(11-12):686-90. doi: 10.1055/s-2002-38264.
Leptin is an adipocyte-secreted hormone that binds hypothalamic receptors and potently decreases food intake. Leptin receptor defects in homozygous mutant Zucker fatty ( fa/fa) rats lead to massive obesity, hyperphagia, decreased energy expenditure, and insulin resistance, while the phenotype of heterozygous ( Fa/fa) lean rats lies between lean ( Fa/Fa) and obese ( fa/fa) rats. Whether heterezygotes exhibit specific changes in lipid metabolism in a diet-responsive manner is not clear. Thus, the specific aim of this study was to test whether the presence of one fa allele modulates lipid metabolism and leptin, and whether these effects are exacerbated by high-fat diet. We demonstrate that the presence of one fa allele significantly increases lipogenesis in adipose tissue assessed by glycerol-3-phosphate dehydrogenase (GPDH) and fatty acid synthase (FAS) activities. FAS is more responsive to high-fat diets than GPDH in Fa/fa rats. Adipose tissue leptin levels are significantly higher in fat pads of Fa/fa compared to Fa/Fa rats. Moreover, Fa/fa rats fed high-fat diet show an additional two-fold increase in leptin levels compared to wild type rats on the same diet. Collectively, these results indicate that the presence of one fa allele increase adipocyte lipogenic enzyme activities, which results in hyperleptinemia concurrent with increased adiposity.
瘦素是一种由脂肪细胞分泌的激素，它与下丘脑受体结合并能显著减少食物摄入量。纯合突变型 Zucker 肥胖（fa/fa）大鼠的瘦素受体缺陷会导致严重肥胖、食欲亢进、能量消耗减少和胰岛素抵抗，而异合子（Fa/fa）瘦大鼠的表型则介于瘦（Fa/Fa）大鼠和肥胖（fa/fa）大鼠之间。杂合子是否以饮食反应性方式表现出脂质代谢的特定变化尚不清楚。因此，本研究的具体目的是测试一个 fa 等位基因的存在是否会调节脂质代谢和瘦素，以及这些影响是否会因高脂饮食而加剧。我们证明，通过甘油-3-磷酸脱氢酶（GPDH）和脂肪酸合酶（FAS）活性评估，一个 fa 等位基因的存在会显著增加脂肪组织中的脂肪生成。在 Fa/fa 大鼠中，FAS 对高脂饮食的反应比 GPDH 更敏感。与 Fa/Fa 大鼠相比，Fa/fa 大鼠脂肪垫中的脂肪组织瘦素水平显著更高。此外，与相同饮食的野生型大鼠相比，喂食高脂饮食的 Fa/fa 大鼠的瘦素水平额外增加了两倍。总体而言，这些结果表明，一个 fa 等位基因的存在会增加脂肪细胞脂肪生成酶的活性，从而导致高瘦素血症并伴有肥胖增加。
