肥胖與自主神經系統的失衡有關，會造成交感神經功能低下與副交感神經功能亢進。然而，文獻較少提及副交感神經膽鹼性受體如何影響能量代謝。因此，本研究欲藉由探討膽鹼性受體在脂肪或肌肉組織中所扮演的角色，來了解肥胖形成原因。首先，以西方點墨法觀察到三種的膽鹼性受體亞型(M1、M2及M3)都存在於脂肪和肌肉組織中。接著，乙醯膽鹼會增加Wistar雄性大白鼠肌肉組織的葡萄糖攝取(glucose uptake)的能力，並呈現劑量相關性。然而，在副睪脂肪細胞中卻會抑制胰島素所刺激的葡萄糖攝取作用。進ㄧ步，利用不同的特異性受體阻斷劑，結果指出肌肉組織藉由M1膽鹼性受體來調控，而脂肪細胞是透過M3膽鹼性受體來調控。此外，利用細胞內訊息的阻斷劑來確認膽鹼性受體，藉由PLC-PKC路徑對脂肪細胞進行調控。最後，離體的脂肪組織在給予乙醯膽鹼刺激，會抑制游離脂肪酸的釋放。若給予bethanechol刺激膽鹼性受體，亦會促進3T3-L1脂肪細胞內脂肪油滴的生成及增加BALB/c小鼠的食慾。綜合上述結果，副交感神經的過度活化確實可以透過膽鹼性受體的訊息來調控身體能量的代謝。

It has been documented that obesity is related to the imbalance of autonomic nervous system, and leads to reduce the sympathetic tone and increase the cholinergic activity. However, little is known how the cholinergic nerves affect the energy metabolism via muscarinic cholinoceptor. The present study aimed at the role of muscarinic cholinoceptor in the adipose tissue and muscle to investigate the possible mechanisms of pathology for obesity. First, the Western blotting analysis appears that all muscarinic cholinoceptor subtypes (M1, M2, M3) were expressed in white adipose tissue (WAT) and muscle in Wistar rats. Moreover, acetylcholine (ACh) increases glucose uptake into isolated muscle in a concentration-dependent manner. However, ACh stimulation attenuates insulin-stimulated glucose uptake into isolated WAT. To use specific muscarinic antagonists, our results also indicate that these effects act in muscles through M1 and in adipocytes through M3 receptor. Adipocytes were pretreated with signal transduction inhibitors to clarify the role of ACh in WAT. Results showed that attenuation of the glucose uptake evoked by ACh is mainly due to the activation of muscarinic M3 receptors in WAT through PLC-PKC pathway. Otherwise, ACh reduced the release of glycerol from WAT in a concentration-dependent manner. Finally, bethanechol, a muscarinic agonist, induces adipogensis in 3T3-L1 cells and increases food intake of BALB/c mice. These results demonstrate that the cholinergic hyperactivity may involve in the altered energy metabolism via an activation of the muscarinic cholinoceptor.

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