Preference for a high fat diet, but not hyperphagia following activation of mu opioid receptors is blocked in AgRP knockout mice.
Preference for a high fat diet, but not hyperphagia following activation of mu opioid receptors is blocked in AgRP knockout mice.
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DOI：
10.1016/j.brainres.2009.12.051
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发表时间：
2010-03-04
期刊：
影响因子：
2.9
通讯作者：
Bray, George A.
中科院分区：
文献类型：
--
作者：
Barnes, Maria J.;Argyropoulos, George;Bray, George A.
mu阿片受体（MOR）的激活使动物贪食，并选择性地增加它们对高脂肪饮食的偏好，而不依赖于它们的饮食偏好。产氧肽Agouti相关肽（AgRP）也会产生贪食并增加对高脂肪饮食的偏好。在本文中，我们验证了在缺乏促氧肽AgRP的情况下，MOR对摄食行为的影响会减弱的假设。免疫组织化学研究表明，MOR共定位于位于弓形核的AgRP神经元上。这一发现与MOR在介导AgRP释放中的作用一致。我们的数据还表明，野生型（FVB）动物更喜欢高脂肪的饮食，而AgRP敲除（AgRP KO）小鼠则没有。AgRP KO小鼠下丘脑MOR mRNA表达与野生型对照无显著差异。在剂量反应实验中，低剂量（0.025μg）的MOR激动剂DAMGO增加了野生型和AgRP KO小鼠的累积食物摄入量。低、中剂量（0.25μg） DAMGO显著增加了野生型动物的高脂饲料摄取量，但对AgRP KO小鼠的高脂饲料摄取量无显著影响。最高剂量的DAMGO （2.5μg）减少了对照组和AgRP KO小鼠的食物摄入量，可能是由于嗜睡。这些数据表明，在没有AgRP的情况下，MOR刺激后对高脂肪饮食的偏好增加会减弱，但食物摄入量的增加（即贪食）却不会减弱。
Activation of mu opioid receptors (MOR) makes animals hyperphagic and selectively increases their preference for a high fat diet independent of their dietary preference. The orexigenic peptide Agouti Related Peptide (AgRP) also produces hyperphagia and increased the preference for a high fat diet. In this paper, we tested the hypothesis that the effect of MOR on feeding behavior will be attenuated in the absence of the orexigenic peptide AgRP. Immunohistochemical studies demonstrated that MOR are co-localized on AgRP neurons located in the arcuate nucleus. This finding is consistent with a role of MOR in mediating the release of AgRP. Our data also demonstrated that the wild-type (FVB) animals preferred a diet high in fat whereas the AgRP knockout (AgRP KO) mice did not. mRNA expression of MOR in the hypothalamus was not significantly different between AgRP KO mice and their wild-type control. In a dose response experiment, the low dose (0.025μg) of a MOR agonist, DAMGO, increased cumulative food intake in wild-type and AgRP KO mice. The low and middle (0.25μg) dose of DAMGO significantly increased the amount of high fat diet eaten by the wild-type animals, but did not significantly change the amount of high fat diet eaten by the AgRP KO mice. The highest dose of DAMGO (2.5μg) reduced food intake in the control and AgRP KO mice, probably due to somnolence. These data demonstrate that the increased preference for a high fat diet after stimulation of MOR is attenuated in the absence of AgRP, but the increase in food intake (i.e. hyperphagia) is not.
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影响因子：
4.8
作者：
Chen, PL;Li, CE;Smith, MS
通讯作者：
Smith, MS
DOI：
10.1152/ajpregu.2000.279.1.r47
发表时间：
2000-07-01
影响因子：
2.8
作者：
Hagan, MM;Rushing, PA;Seeley, RJ
通讯作者：
Seeley, RJ
影响因子：
3.6
作者：
MARKSKAUFMAN, R
通讯作者：
MARKSKAUFMAN, R
影响因子：
56.9
作者：
Hill, JO;Peters, JC
通讯作者：
Peters, JC
影响因子：
4.8
作者：
Brugman, S;Clegg, DJ;Seeley, RJ
通讯作者：
Seeley, RJ