短鏈脂肪酸對棕櫚酸誘發之C2C12肌肉細胞發炎反應及胰島素阻抗之影響

長期西式飲食型態及靜態生活方式，使體重增加，影響胰島素的敏感性，研究資料證實，胰島素阻抗是罹患代謝性症候群及糖尿病的危險因子，雖然肥胖造成胰島素阻抗機轉不是很清楚，但與血漿過多的游離脂肪酸及發炎反應有密切的關係。短鏈脂肪酸 —丙酸、丁酸，為人體腸道細菌發酵代謝纖維質的產物，可以調節腸道免疫功能、降低膽固醇及抗發炎反應。本研究目的，主要探討短鏈脂肪酸對飽和棕櫚酸誘發C2C12肌肉細胞發炎反應及胰島素阻抗之影響。實驗結果顯示，給予C2C12肌肉細胞丙酸及丁酸，可以降低棕櫚酸誘發的磷酸化protein kinase c-θ、extracellular-regulated protein kinase 1/2及P38 mitogen-activated kinase，減少轉錄因子nuclear factor-κB活性，降低促發炎反應物質cyclooxygenase-2、interleukin-6、tumor necrosis factor-α表現。在基礎狀態下，丙酸及丁酸可恢復棕櫚酸降低磷酸化AMP-activated protein kinase 及Akt substrate of 160 kDa。此外，肌肉細胞給予棕櫚酸，明顯降低胰島素誘發的磷酸化Akt及減少肌肉細胞對葡萄糖的攝取，造成胰島素阻抗，處理丙酸及丁酸，可以恢復棕櫚酸抑制磷酸化Akt，增加肌肉細胞對葡萄糖的攝取。經由本研究證實，短鏈脂肪酸在C2C12肌肉細胞，具有抑制棕櫚酸誘發的發炎反應及改善胰島素阻抗之功效。

The western style dietary pattern and inactive lifestyle have been shown to increase insulin resistance and to be a risk factor for developing metabolic syndrome and diabetes. It was reported that elevated plasma free fatty acid is response to the inflammation and insulin resistance in diabetic patients and nondiabetic subjects. Propionate (PrA) and butyrate (BuA) short chain fatty acids (SCFAs) are metabolic products of fiber by intestinal bacteria fermentation, SCFAs could regulate immune function and inflammation. Here, the effects of SCFAs on palmitate (PA) -induced inflammation and insulin resistance in C2C12 skeletal muscle cells were examined. Exposure of C2C12 cells to PA enhanced phosphylation of protein kinase c-θ, mitogen-activated protein kinase. Moreover, PA increased activity of transcription factor nuclear factor-κB and production of proinflammatory mediators, such as, cyclooxygenase-2, interleukin-6 and tumor necrosis factor-α. PrA and BuA reversed palmitate down-regulated of phosphorylation of AMP-activated protein kinase and Akt substrate of 160 kDa in basal state. PA-induced insulin resistance as the evidence by decrease phosphylation of Akt activation and glucose uptake in insulin stimulated C2C12 cells. Co-incubation of C2C12 cells with PA, PrA and BuA reversed PA induced inflammatory events and insulin resistance. These data demonstrated that SCFAs are effective in inhibition of PA-induced inflammation and insulin resistance in C2C12 skeletal muscle cells.