菊苣纖維延緩高脂飲食引起大白鼠骨骼肌減少的機轉-調節發炎作用及內質網壓力

高脂飲食 (High fat diet, HFD) 使過多的脂質沉積到骨骼肌中可能會對肌肉功能產生發炎反應，損害骨骼肌的代謝和收縮功能。過去文獻指出菊苣纖維可改善腸道菌相，而改善腸道菌相有助於降低 發炎作用。因此本研究想進一步探討菊苣纖維在 HFD 誘導的動物肥 胖模式中，骨骼肌中的促炎細胞因子是否具改善作用。在本次實驗 架構中，將使用五週齡大鼠，餵食 HFD 誘導肥胖後，於第三週分為 四組:Control 組、HFD 組、HFD+Inulin 組、HFD+Atorvastatin 組， 介入菊苣纖維 19 週，隨後取骨骼肌 (股四頭肌、腓腸肌、脛前肌、 比目魚肌、伸趾長肌) 進行測重。分別取比目魚肌 (I 型肌肉) 、脛 前肌 (II 型肌肉) 進行蛋白分析，結果顯示菊苣纖維介入會使肌細胞 生成素 (Myogenin, MyoG) 表現量明顯增加。菊苣纖維介入使促炎 細胞因子 IL-6、TNF-α、MCP-1 表現量顯著降低及並減少 pNF-κB、 TLR4 蛋白量。菊苣纖維可減少骨骼肌細胞中內質網壓力 (Endoplasmic reticulum stress, ER stress)，降低 IRE1α、GRP78、 PERK、pEIF2α、XBP1s 表現量，菊苣纖維同時減少 Ubiquitin、 PARP、Cleaved-PARP 表現量，顯示細胞凋亡減少，藉此以穩定細胞功能並降低肌少，本研究結果顯示在肥胖個體補充菊苣纖維可降低骨骼肌發炎作用及減少內質網壓力以減緩肌少的風險。

High-fat diet (HFD) causes excessive lipid deposition into skeletal muscles, which may have a negative impact on muscle function and impair the metabolic and contractile functions of skeletal muscles. Previous literature has shown that inulin can improve intestinal flora consequently to reduce inflammation. Therefore, this study was aimed to explore whether inulin can alter pro-inflammatory cytokines in skeletal muscle in HFD-induced obesity. In this experiment, five-week-old rats were fed HFD for 2 weeks to induce obesity, then the obese rats were divided into four groups as the followings, control, HFD, HFD+Inulin, HFD+Atorvastatin. After 19 weeks, skeletal muscles (quadriceps, tibialis anterior, gastrocnemius, soleus, extensor digitorum longus muscle) were measured; the soleus (type I) and tibialis anterior (type II) muscles were carried out the protein analysis. The results showed that inulin significantly increased the expression of myogenin (MyoG); reduced the expression levels of pro-inflammatory cytokines IL-6, TNF-α, and MCP- 1; reduced the protein levels of pNF-κB and TLR4. Inulin reduce the protein levels in endoplasmic reticulum stress (ER stress), including IRE1α, GRP78, PERK, pEIF2α, and XBP1s, in skeletal muscle cells. Inulin reduced the expression of ubiquitin, PARP, and Cleaved-PARP to show the reduction of cell apoptosis, thereby stabilizing cell function and reducing sarcopenia. In the current study, the results show that supplementing inulin in the obese can reduce skeletal muscle inflammation and endoplasmic reticulum stress to mitigate the risk of sarcopenia.