Oleoylethanolamide and Human Neural Responses to Food Stimuli in Obesity
Oleoylethanolamide and Human Neural Responses to Food Stimuli in Obesity
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DOI：
10.1001/jamapsychiatry.2014.1215
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发表时间：
2014-11-01
期刊：
影响因子：
25.8
通讯作者：
Leweke, F. Markus
中科院分区：
文献类型：
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作者：
Grosshans, Martin;Schwarz, Emanuel;Leweke, F. Markus
肥胖已成为主要的健康威胁，但其生物学基础仍不清楚，阻碍了寻找新的治疗方法。在这里，我们研究了油脂乙醇酰胺，这是一种天然存在的脂质，显然与动物的体重调节有关。然而，它在人类体重调节和肥胖中的作用仍不清楚。目的：探讨肥胖患者和对照组的血浆油脂乙醇酰胺水平与体重指数（BMI，以体重公斤除以身高米的平方计算）和功能性磁共振成像对食物刺激的反应之间的关系。设计,设置。21名肥胖患者和24名匹配的对照组进行病例对照研究。肥胖被定义为身体质量指数至少为30。参与者的平均年龄为40.8岁，bmi从18.2到47.5不等。主要结局和测量血浆油脂乙醇酰胺水平与肥胖、BMI和对食物刺激的功能性磁共振成像反应之间的相互作用。结果油脂乙醇酰胺与BMI的相关性因个体是否肥胖而有显著差异（P = 0.02）。在肥胖个体中，油脂乙醇酰胺与BMI呈正相关（P = 0.06, rho = 0.42），而在非肥胖对照组中，这种关系呈负相关（P = 0.07, rho = -0.34）。同样，我们发现油基乙醇酰胺水平和肥胖对与食物相关的大脑皮层区奖赏处理和内感受信号激活的显著相互作用（P = 0.009）。具体来说，非肥胖者的高油脂乙醇酰胺水平有更高的岛脑活动（P < 0.001, rho = 0.70）；同样，肥胖患者的相关性呈反比（P = 0.11, rho = -0.36）。这些影响与血浆中瘦素和阿南达明的水平无关，表明油基乙醇酰胺在饥饿相关的内感受信号传导中具有独立作用。在功能性磁共振成像任务中，对食物渴望的分析表明，在非肥胖个体中，已识别的大脑区域可能与抑制喜欢食物的反应有关。结论与相关性本研究提示，油基乙醇酰胺介导的信号在人类对食物渴望和肥胖的享乐调节中起重要作用，因此可能是开发新型抗肥胖药物的有价值靶点。
IMPORTANCE Obesity has emerged as a leading health threat but its biological basis remains insufficiently known, hampering the search for novel treatments. Here, we study oleoylethanolamide, a naturally occurring lipid that has been clearly implicated in weight regulation in animals. However, its role for weight regulation and obesity in humans is still unclear.OBJECTIVE To investigate associations between plasma oleoylethanolamide levels and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and functional magnetic resonance imaging response to food stimuli in obese patients and matched control participants.DESIGN, SETTING. AND PARTICIPANTS Case-control study of 21 obese patients and 24 matched control participants. Obesity was defined as having a BMI of at least 30. The mean age of participants was 40.8 years and BMIs ranged from 18.2 to 47.5.MAIN OUTCOMES AND MEASURES Interactions between plasma oleoylethanolamide levels and obesity on BMI and functional magnetic resonance imaging response to food stimuli.RESULTS Associations between oleoylethanolamide and BMI differed significantly depending on whether individuals were obese or not (P = .02). In obese individuals, oleoylethanolamide showed a trend toward a positive correlation with BMI (P = .06, rho = 0.42), while this relationship was inverse for nonobese control participants (P = .07, rho = -0.34). Similarly, we found significant interactions between oleoylethanolamide levels and obesity on food-related brain activation in cortical areas associated with reward processing and interoceptive signaling (P = .009). Specifically, nonobese individuals with higher oleoylethanolamide levels had higher insular brain activity (P < .001, rho = 0.70); again, the relationship trended to be inverse for obese patients (P = .11, rho = -0.36). These effects were not associated with plasma levels of leptin and anandamide, suggesting an independent role of oleoylethanolamide in hunger-associated interoceptive signaling. Analysis of food craving during the functional magnetic resonance imaging task suggested that the identified brain areas may be involved in suppressing food-liking reactions in nonobese individuals.CONCLUSIONS AND RELEVANCE This study suggests that oleoylethanolamide-mediated signaling plays an important role for hedonic regulation of food craving and obesity in humans and thus may be a valuable target for developing novel antiobesity drugs.