Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: reversal upon weight loss
Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: reversal upon weight loss
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DOI：
10.1038/sj.ijo.0802640
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发表时间：
2004-07-01
影响因子：
4.9
通讯作者：
Stricker-Krongrad, A
中科院分区：
文献类型：
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作者：
Perreault, M;Istrate, N;Stricker-Krongrad, A
背景：生长激素释放肽是生长激素促分泌素受体 (GHS-R) 的内源性配体，已知可以增加瘦人和啮齿动物的食物摄入量。此外，在瘦啮齿类动物中，饥饿素水平会因禁食而增加，而在人类中，饥饿素水平会在餐前升高，这表明饥饿素在进餐开始中发挥着重要作用。然而，在肥胖人群中，与瘦人相比，循环胃饥饿素水平显着降低。 目的：评估肥胖个体的循环胃饥饿素水平以及胃饥饿素敏感性是否降低，以限制其对食物摄入的影响。设计：使用饲喂饲料、低脂饮食 (LFD) 或高脂饮食 (HFD) 的瘦 C57BL/6J 小鼠来测定生长素释放肽调节和分泌以及生长素释放肽敏感性。 测量：测量低脂和高脂喂养小鼠的血浆生长素释放肽水平。在粗粮、低脂和高脂喂养的小鼠中测量了胃饥饿素诱导的食物摄入量。结果：我们测量了分别以 LFD 或 HFD 喂养的瘦小鼠和饮食诱导的肥胖小鼠的胃饥饿素水平。我们观察到，肥胖小鼠的生长素释放肽分泌不仅减少，而且其昼夜调节也丧失。此外，我们未能观察到禁食和重新进食后生长素释放肽分泌的任何变化。此外，我们观察到，与喂食食物或 LFD 的瘦小鼠相比，肥胖小鼠对外源性生长素释放肽的促食欲作用的敏感性降低。肥胖小鼠对生长素释放肽的不敏感性在减肥后得到改善。结论：总之，这些结果表明，饮食诱导的肥胖小鼠生长素释放肽的分泌和调节受到损害，并表明抑制生长素释放肽可以防止减肥后体重反弹。
BACKGROUND: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), is known to increase food intake in lean humans and rodents. In addition, ghrelin levels are increased by fasting in lean rodents and are elevated before meals in humans, suggesting an important role for ghrelin in meal initiation. However, in obese human, circulating ghrelin levels were found to be significantly reduced as compared to lean individuals.OBJECTIVES: To evaluate whether circulating ghrelin levels, as well as ghrelin sensitivity, are decreased in obese individuals in order to limit its effect on food intake. DESIGN: Lean C57BL/6J mice fed a chow, a low- (LFD) or a high-fat diet (HFD) were used to determine ghrelin regulation and secretion as well as ghrelin sensitivity.MEASUREMENTS: Plasma ghrelin levels were measured in low- and high-fat fed mice. Ghrelin-induced food intake was measured in chow, low- and high-fat fed mice.RESULTS: We measured ghrelin levels in lean and diet-induced obese mice, fed on an LFD or an HFD, respectively. We observed that not only ghrelin secretion was reduced in obese mice but its diurnal regulation was also lost. In addition, we failed to observe any change in ghrelin secretion upon fasting and refeeding. Moreover, we observed that the sensitivity to the orexigenic effects of exogenous ghrelin was reduced in obese mice when compared to lean mice fed a chow or a LFD. The insensitivity of obese mice to ghrelin was improved upon weigh loss.CONCLUSION: Altogether, these results indicate that ghrelin secretion and regulation is impaired in dietary-induced obesity in mice and suggest that ghrelin inhibition could prevent weight regain after weight loss.