Ankaflavin 對高脂飲食下動物胰島素訊號傳遞及脂質累積之影響

Abstract

本研究以 ankaflavin 配合高脂飲食誘導模式，並同時以腹腔注射 GW9662 (PPAR gamma 拮抗劑)，評估 ankaflavin 對於動物脂肪堆積與胰島素敏感度的調控。結果發現，ankaflavin 能藉由調節PPAR gamma 以降低高脂飲食誘導產生之高血糖及高胰島素症，其降低率分別為 36.6% 及 60%，並可減少血清與肝組織中三酸甘油酯與總膽固醇。在細胞實驗中以 ankaflavin 與另一結構相似之黃色素monascin 處理 3T3-L1 小鼠成熟脂肪細胞，結果顯示 ankaflavin 與 monascin可活化脂肪細胞胰島素訊號傳遞並促進葡萄糖吞噬 (glucose uptake)。此外，本研究首次證實ankaflavin 可藉由PPAR gamma 調節脂肪細胞大小與數目，並減少脂肪細胞平均半徑，提升脂肪細胞生產 adiponectin 並降低 resistin 及 leptin。顯示 ankaflavin 可能藉由調控脂肪組織對胰島素敏感度，並活化 adipokines 下游路徑而達到改善高脂誘導胰島素抗性。

In order to investigate whether ankaflavin can regulate lipid metabolism and insulin sensitivity through PPAR gamma pathways, we fed mice with high-fat diet and ankaflavin and performed i.p. injection of GW9662 (PPAR gamma antagonist) simultaneously. In vitro, we examined the expressions of insulin signaling proteins in differentiated 3T3-L1 cells treated with ankaflavin and another structural similar Monascus yellow pigment—monascin. Results showed that ankaflavin down-regulated triglyceride and total cholesterol in serum and liver tissue. Ankaflavin could also ameliorate hyperglycemia and hyperinsulinemia symptoms elicited by high-fat diet, the decrease ratio was 36.6% and 60% respectively, which might be due to its abilities to improve insulin signaling and glucose uptake in differentiated 3T3-L1 cells. Moreover, we discovered for the first time that ankaflavin could regulate the size and the amount of adipocytes in a PPAR gamma dependent way, and reduce average radius of adipocytes as well. Also, ankaflavin elevate the levels of adiponectin and decrease levels of resistin and leptin via PPAR gamma pathways in vivo and in vitro, which might activate signalings related to lipid metabolism and insulin signaling.