Y2Y4 receptor double knockout protects against obesity due to a high-fat diet or Y1 receptor deficiency in mice.
Y2Y4 receptor double knockout protects against obesity due to a high-fat diet or Y1 receptor deficiency in mice.
复制标题
Y2Y4 受体双敲除可防止小鼠因高脂肪饮食或 Y1 受体缺乏而导致的肥胖。
DOI：
10.2337/diabetes.55.01.06.db05-0472
复制
发表时间：
2006
期刊：
影响因子：
7.7
通讯作者：
H. Herzog
中科院分区：
文献类型：
--
作者：
A. Sainsbury;H. Bergen;Dana Boey;Darja Bamming;G. Cooney;Shu Lin;M. Couzens;N. Stroth;N. Lee;D. Lindner;N. Singewald;T. Karl;L. Duffy;R. Enriquez;Katy Slack;G. Sperk;H. Herzog
神经肽Y受体是能量稳态的关键调节因子，但Y受体和环境在这一过程中的功能相互作用和相对贡献尚不清楚。我们测量了自由饮食的正常或高脂肪食物对能量平衡的影响，在小鼠与单，双，或三重缺陷的Y1，Y2，或Y4受体。然而野生型小鼠发展了饮食诱导的肥胖，Y2Y4双敲除小鼠没有。相比之下，Y1基因敲除或Y1Y2或Y1Y4受体双敲除小鼠出现了加重的饮食诱导的肥胖综合征。值得注意的是，Y2Y4缺乏的抗肥胖作用比Y1缺乏的致肥胖作用更强，因为Y1Y2Y4三重敲除在高脂肪饮食中不会产生肥胖。Y2Y4基因敲除者对饮食诱导的肥胖的抵抗与在总体力活动没有变化的情况下减少食物摄入和改善葡萄糖耐量有关。粪便中游离脂肪酸浓度显着增加Y2Y4基因敲除与显着减少胆汁酸池和显着改变肠道形态。此外，饮食诱导的肥胖（野生型和Y1受体敲除小鼠）下丘脑阿黑皮素原表达降低，但在高脂饮食喂养的肥胖抗性Y2Y4受体敲除小鼠中则没有。因此，Y2和Y4受体的缺失至少部分地通过食物摄入和下丘脑阿黑皮素原表达的变化协同地防止饮食诱导的肥胖。
Neuropeptide Y receptors are critical regulators of energy homeostasis, but the functional interactions and relative contributions of Y receptors and the environment in this process are unknown. We measured the effects of an ad libitum diet of normal or high-fat food on energy balance in mice with single, double, or triple deficiencies of Y1, Y2, or Y4 receptors. Whereas wild-type mice developed diet-induced obesity, Y2Y4 double knockouts did not. In contrast, Y1 knockout or Y1Y2 or Y1Y4 receptor double knockout mice developed an exacerbated diet-induced obesity syndrome. Remarkably, the antiobesity effect of Y2Y4 deficiency was stronger than the obesogenic effect of Y1 deficiency, since Y1Y2Y4 triple knockouts did not develop obesity on the high-fat diet. Resistance to diet-induced obesity in Y2Y4 knockouts was associated with reduced food intake and improved glucose tolerance in the absence of changes in total physical activity. Fecal concentration of free fatty acids was significantly increased in Y2Y4 knockouts in association with a significantly reduced bile acid pool and marked alterations in intestinal morphology. In addition, hypothalamic proopiomelanocortin expression was decreased in diet-induced obesity (in both wild-type and Y1 receptor knockout mice) but not in obesity-resistant Y2Y4 receptor knockout mice fed a high-fat diet. Therefore, deletion of Y2 and Y4 receptors synergistically protects against diet-induced obesity, at least partially via changes in food intake and hypothalamic proopiomelanocortin expression.
影响因子：
7.7
作者：
Mizuno, TM;Kleopoulos, SP;Mobbs, CV
通讯作者：
Mobbs, CV