中鏈脂肪酸對棕櫚酸所誘發之C2C12肌肉細胞發炎反應之影響

發炎反應（inflammatory response），係指身體組織在面對體內損傷因子如氧化壓力、組織受傷或外來物入侵等狀況時所產生之保護反應，但若損傷因子持續存在於體內，急性發炎則會進展為慢性發炎。先前文獻證實慢性發炎在多種疾病的發展過程中扮演關鍵角色，如糖尿病、脂肪肝及動脈粥狀硬化。研究指出，當給予C2C12肌肉細胞飽和脂肪酸棕櫚酸 (palmitate, 16:0)，會促進發炎物質IL-6及TNF-α分泌，誘發發炎反應，進而造成胰島素阻抗。中鏈飽和脂肪酸其攜帶碳數介於6-14之間，在臨床上常取代長鏈脂肪酸被應用於重症病患的營養介入，增加對脂肪的代謝與利用，但目前仍少有文獻探討中鏈飽和飽和脂肪酸對於發炎反應之影響，故本研究主要目的將探討中鏈飽和脂肪酸－肉豆蔻酸 (mystiric acid，C14:0)和月桂酸 (lauric acid，C12:0)對於palmitate誘發之發炎反應調控。實驗結果發現，單獨給予palmitate下，可促進C2C12肌肉細胞中PKC-θ磷酸化、轉錄因子NF-κB活化、引起發炎物質COX-2、IL-6及TNF-α表現；而同劑量中鏈飽和脂肪酸mystiric acid和lauric acid雖然會稍微誘發發炎物質COX-2、IL-6及TNF-α表現，但誘發程度低於palmitate。mystiric acid和lauric acid可抑制PKC-θ磷酸化、減少IκBα降解、抑制NF-κB活化，進而抑制PA所誘發之COX-2表現。上述結果證實中鏈飽和脂肪酸mystiric acid和lauric acid可能透過抑制PKC-θ/IκBα/NFκB路徑，而進一步調控PA所誘發之COX-2表現。

關鍵字

C2C12肌肉細胞；棕櫚酸；肉豆蔻酸；月桂酸；發炎反應

並列摘要

Inflammatory response refers to the protection of body tissues from appearance of stimulating factor such as injury, foreign object intrusion and oxidative stress. However, chronic inflammation plays an important role in pathogenesis of many diseases, including diabetes, fatty liver and atherosclerosis. It was reported that exposure of C2C12 skeletal muscle cells with the saturated fatty acid palmitate (16:0) could increase expression of proinflammatory cytokines Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) to induce inflammation which may be related to insulin resistance. Medium-chain fatty acids (MCFA) are saturated fatty acids, carrying carbon number between 6-14. It is often used in clinical nutrition intervention for critically ill patients to instead of long chain fatty acids to improve fat utilization for critically ill patients. The effect of MCFA on inflammation still do not understand so in this study, we explore the role of MCFA, lauric acid (C12:0) and mystiric acid (C14:0) in C2C12 Cells. Although the MCFA, lauric acid and mystiric acid slightly induced COX-2, IL-6 and TNF-α expression, but induced lower than palmitate.Moreover, co-incubation of cells with palmitate and lauric acid or mystiric acid reversed palmitate-induced PKC-θ phosphorylation, NF-κB activation and COX-2 expression. These findings may suggest that MCFA lauric acid and mystiric acid could decrease palmitate-induced COX-2 expression through inhibition of PKC-θ/IκBα/NFκB pathway.

並列關鍵字

C2C12 skeletal muscle cell ； palmitate ； lauric acid

參考文獻

24. James T. Wu and Lily L. Wu. (2007) Acute and Chronic Inflammation: Effect of the Risk Factor (s) on the Progression of the Early Inflammatory Response to the Oxidative and Nitrosative Stress.

2. Akito Kadotani, Yo Tsuchiya, Hiroyasu Hatakeyama, Hideki Katagiri, and Makoto Kanzaki. (2009) Different impacts of saturated and unsaturated free fatty acids on COX-2 expression in C2C12 myotubes. Am J Physiol Endocrinol Metab 297: E1291–E1303

3. Albert S. Baldwin. (2001) Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB. J Clin Invest. 107(3): 241–246

4. Andre’C Bach, ScD and Vigen K Babayan. (1982) Medium-chain triglycerides: an update. Am J Clin Nutr 36:950-962

5. Arion Kennedy, Kristina Martinez, Chia-Chi Chuang, Kathy LaPoint, and Michael McIntosh. (2009) Saturated Fatty Acid-Mediated Inflammation and Insulin Resistance in Adipose Tissue: Mechanisms of Action and Implications. American Society for Nutrition. J. Nutr. 139: 1–4

國際替代計量

中鏈脂肪酸對棕櫚酸所誘發之C2C12肌肉細胞發炎反應之影響

全文下載

主題瀏覽