Hyperleptinemia is required for the development of leptin resistance.
Hyperleptinemia is required for the development of leptin resistance.
复制标题
DOI：
10.1371/journal.pone.0011376
复制
发表时间：
2010-06-29
期刊：
影响因子：
3.7
通讯作者：
Friedman JM
中科院分区：
文献类型：
--
作者：
Knight ZA;Hannan KS;Greenberg ML;Friedman JM
瘦素通过向大脑发出储存为脂肪的能量的信号来调节体重。在大多数肥胖者中，这种负反馈循环会被扰乱，导致一种称为瘦素抵抗的状态。瘦素抵抗的生理原因仍然知之甚少。在这里，我们测试了这样的假设，即高瘦素血症是饮食诱导的肥胖小鼠发生瘦素抵抗所必需的。我们发现，血浆瘦素水平被限制在瘦素水平的小鼠会因高脂肪饮食而发生肥胖，而这种肥胖的程度与野生型对照组没有什么区别。然而，这些血浆瘦素水平持续较低的肥胖动物，即使在长期接触高脂肪饮食后，仍对外源瘦素高度敏感。这表明，单靠饮食脂肪不足以阻止瘦素的反应。数据还表明，高瘦素血症本身可能通过下调细胞对瘦素的反应而导致瘦素抵抗，就像其他激素所显示的那样。
Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones.
登录
查看更多内容
影响因子：
15.9
作者：
Bjornholm, Marie;Munzberg, Heike;Myers, Martin G., Jr.
通讯作者：
Myers, Martin G., Jr.
影响因子：
56.9
作者：
Bouret, SG;Draper, SJ;Simerly, RB
通讯作者：
Simerly, RB
影响因子：
4.8
作者：
Münzberg, H;Flier, JS;Bjorbæk, C
通讯作者：
Bjorbæk, C
影响因子：
82.9
作者：
Howard, JK;Cave, BJ;Flier, JS
通讯作者：
Flier, JS
影响因子：
29
作者：
Hedbacker, Kristina;Birsoy, Kivanc;Friedman, Jeffrey M.
通讯作者：
Friedman, Jeffrey M.