N-Oleoylglycine-Induced Hyperphagia Is Associated with the Activation of Agouti-Related Protein (AgRP) Neuron by Cannabinoid Receptor Type 1 (CB1R)
N-Oleoylglycine-Induced Hyperphagia Is Associated with the Activation of Agouti-Related Protein (AgRP) Neuron by Cannabinoid Receptor Type 1 (CB1R)
复制标题
N-油酰甘氨酸诱导的食欲亢进与 1 型大麻素受体 (CB1R) 激活刺豚鼠相关蛋白 (AgRP) 神经元有关。
DOI：
10.1021/acs.jafc.6b05281
复制
发表时间：
2017-02-08
影响因子：
6.1
通讯作者：
Shu, Gang
中科院分区：
文献类型：
--
作者：
Wu, Junguo;Zhu, Canjun;Shu, Gang
N-酰基氨基酸（NAAA）是动物源性食品中常见的脂肪酸和氨基酸的共轭产物。我们比较了N-花生四烯酰甘氨酸（NAGly）、N-花生四烯酰丝氨酸（NASer）和N-油酰甘氨酸（OLGly）对体内食物摄入和体外Agouti相关蛋白（AgRP）神经元[Ca 2 +]i的影响，以确定这些化合物在能量稳态中的作用。下丘脑神经肽的表达和焦虑行为响应OLGly也进行了测试。为了进一步确定OLGly对食物摄入的潜在机制，我们首先检测了潜在OLGly受体的表达水平。将大麻素受体1型（CB 1 R）拮抗剂与OLGly共处理，分析AgRP神经元的激活，包括[Ca 2 +]i，PKA，CREB和c-Fos的表达水平，以及神经肽的分泌。结果表明，仅腹腔注射OLGly（6 mg/kg）可引起大鼠摄食过多，而不改变下丘脑神经肽的表达和焦虑样行为。此外，20 μM OLGly可显著增强AgRP神经元中[Ca 2 +]i、c-Fos蛋白表达以及培养基中AgRP含量。OLGly诱导的AgRP神经元的激活被CB 1 R特异性拮抗剂AM 251完全消除。总之，本研究首次证明了OLGly诱导的摄食过多与CB 1 R激活AgRP神经元的相关性。这些发现为OLGly调节能量稳态的研究和应用开辟了途径。
N-Acyl amino acids (NAAAs) are conjugate products of fatty acids and amino acids, which are available in animal-derived food. We compared the effects of N-arachidonoylglycine (NAGly), N-arachidonoylserine (NASer), and N-oleoylglycine (OLGly) on in vivo food intake and in vitro [Ca2+]i of Agouti-related protein (AgRP) neurons to identify the role of these compounds in energy homeostasis. Hypothalamic neuropeptide expression and anxiety behavior in response to OLGly were also tested. To further identify the underlying mechanism of OLGly on food intake, we first detected the expression level of potential OLGly receptors. The cannabinoid receptor type 1 (CB1R) antagonist was cotreated with OLGly to analyze the activation of AgRP neuron, including [Ca2+]i, expression levels of PKA, CREB, and c-Fos, and neuropeptide secretion. Results demonstrated that only OLGly (intrapertioneal injection of 6 mg/kg) can induce hyperphagia without changing the expression of hypothalamic neuropeptides and anxiety-like behavior. Moreover, 20 μM OLGly robustly enhances [Ca2+]i, c-Fos protein expression in AgRP neuron, and AgRP content in the culture medium. OLGly-induced activation of AgRP neuron was completely abolished by the CB1R-specific antagonist, AM251. In summary, this study is the first to demonstrate the association of OLGly-induced hyperphagia with activation of the AgRP neuron by CB1R. These findings open avenues for investigation and application of OLGly to modulate energy homeostasis.