補充琉璃苣油改善高脂飲食中年小鼠發炎、氧化壓力及胰島素功能之功效

肥胖及老化過程分別皆會造成白色脂肪組織含量增加，並誘使脂質異位沉積於非脂肪組織，經由胰島素阻抗、氧化壓力與發炎反應上調，導致胰島素功能下降。研究發現，老化過程伴隨肥胖易引發肥胖型肌少症(Sarcopenic obesity)，並與第二型糖尿病具有負面的雙向連結。過去文獻指出琉璃苣油中富含的γ-次亞麻油酸(Gamma-Linolenic acid, GLA)可改善氧化壓力、發炎及胰島素功能。本研究探討補充琉璃苣油是否能改善長期高脂飲食中年肥胖小鼠肝臟與骨骼肌氧化壓力、發炎、胰島素功能及肌肉萎縮功效及其相關可能機制。結果顯示，補充琉璃苣油可改善高脂飲食中年肥胖小鼠空腹血糖、葡萄糖耐受性及胰臟β細胞功能(Homeostasis Model Assessment-β cell function, HOMA-%β)。補充琉璃苣油可能經由增加肝臟及骨骼肌單磷酸腺苷活化蛋白激酶(AMP-activated protein kinase, AMPK)、Sirtuin-1 (SIRT1)及過氧化物酶體增殖物活化受體γ-共激活因子1 α (PPARγ coactivator-1 α, PGC-1α)能量代謝訊息傳遞因子表現，改善體內三酸甘油酯(Triglycerides, TG)堆積，以及胰島素接受器受質-1 (Insulin receptor substrate-1, IRS-1)與蛋白激酶B(Protein kinase B, Akt)胰島素訊息傳遞因子表現。此外，補充琉璃苣油顯著改善高脂飲食中年小鼠肝臟與骨骼肌抗氧化力，即NADPH氧化酶4 (NADPH oxidase 4, Nox4)、p22-吞噬細胞氧化酶(p22-phagocyte oxidase, p22phox)、NQO1 [NAD(P)H:Quinone Oxidoreductase 1]、超氧化物歧化酶(Superoxide Dismutase, SOD)、穀胱甘肽過氧化酶(Glutathione Peroxidase, GPx)和穀胱甘肽還原酶(Glutathione Reductase, GR)，與其相關核蛋白Nrf2 (Nuclear factor erythroid 2-related factor 2)。補充琉璃苣油亦降低肝臟與骨骼肌促發炎細胞激素，即腫瘤壞死因子α (Tumor Necrosis Factor-α, TNF-α)、介白素-1β (Interleukin-1β, IL-1β)和介白素-6 (Interleukin-6, IL-6)，與肝臟發炎相關因子，即單核球趨化蛋白-1 (Monocyte Chemoattractant Protein-1, MCP-1/Ccl2)、分化群36 (Cluster of differentiation 36, CD36)、分化群31 (Cluster of differentiation 31, CD31)和NLRP3 (NLR family pyrin domain containing 3)。值得注意的是，補充琉璃苣油改善高脂飲食誘發中年肥胖小鼠骨骼肌發炎與蛋白質異化作用相關因子表現，包括發炎相關蛋白訊息傳遞因子細胞外調節蛋白激酶(Extracellular signal‑regulated kinase 1/2, ERK1/2)、P38、核蛋白核因子-κB (Nuclear Factor-kappa B, NF-κB)與核蛋白C/EBPδ (CCAAT/Enhancer Binding Proteins δ)，肌凝蛋白重鏈(Myosin Heavy Chain, MyHC)，以及泛素-蛋白酶路徑(Ubiquitin-Proteasome pathway, UPP)和自噬-溶酶體路徑(Autophagy-Lysosome pathway, ALP)相關指標Atrogin-1、MuRF-1與Beclin-1。綜合以上結果得知，補充琉璃苣油有助於改善高脂飲食中年肥胖小鼠肝臟與骨骼肌氧化壓力、發炎與胰島素功能，以及骨骼肌肉萎縮。

關鍵字

琉璃苣油；胰島素功能；發炎；氧化壓力；肌肉萎縮

並列摘要

Obesity and aging can increase white adipose tissue mass respectively, and then elicit ectopic fat deposition in non-adipose tissues, which induce insulin dysfunction by enhancing insulin resistance, oxidative stress and inflammation. The studies suggested aging along with obesity would contribute to Sarcoprnic obesity, and had negative bidirectional relationship between type 2 diabetes and sarcopenia obesity. It has been pointed out Borage oil contained high amounts of gamma-linolenic acid (GLA) could improve oxidative stress, inflammation and insulin function. Thus, this study, was conducted to explore the potential effects and mechanisms of borage oil supplementation on improving inflammation, oxidative stress and insulin function in liver and skeletal muscle as well as muscle atrophy in long-term high-fat diet-induced middle-aged obese mice. The results showed that borage oil supplementation significantly ameliorated fasting blood sugar, glucose tolerance and Homeostasis Model Assessment-β cell function (HOMA-%β) in middle-aged obese mice fed with high-fat diet. Treatment with borage oil also improved internal triglycerides (TG) accumulation and insulin signaling fators of serine phosphorylation of insulin receptor substrate-1 (IRS-1) along with protein kinase B (Akt) expression probably through energy metabolism by AMP-activated protein kinase (AMPK), Sirtuin-1 (SIRT1) and PPARγ coactivator-1 α (PGC-1α) signaling transduction. Furthermore, dietary borage oil markedly promoted antioxidant capacity, such as NADPH oxidase 4 (Nox4), p22-phagocyte oxidase (p22phox), NAD(P)H:Quinone Oxidoreductase 1 (NQO1), Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Glutathione Reductase(GR) and nucleoprotein Nuclear factor erythroid 2-related factor 2 (Nrf2) in liver and skeletal muscle. The data also suggested orally administered borage oil significantly reduced inflammatory cytokines [e.g., Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6)] in liver and skeletal muscle, as well as inflammation-related fators triglycerides and inflammation-related factors [e.g. Chemokine (C-C motif) Ligand 2 (MCP-1/Ccl2), Cluster of differentiation 36 (CD36), Cluster of differentiation 31 (CD31) and NLR family pyrin domain containing 3 (NLRP3) in liver. It is noteworthy that consumption of borage oil ameliorated expression of muscle inflammation and atrophy-related factors, such as inflammation-related signaling fators [e.g., Extracellular signal‑regulated kinase 1/2 (ERK1/2), P38, nuclear proteins of Nuclear Factor-kappa B (NF-κB) and CCAAT/Enhancer Binding Proteins δ (C/EBPδ)], Myosin Heavy Chain (MyHC), along with markers of Ubiquitin-Proteasome pathway (UPP) and Autophagy-Lysosome pathway (ALP) (e.g., Atrogin-1, MuRF-1 and Beclin-1) in HFD-induced middle-aged obese mice. In summary, these results suggested that dietary borage oil ameliorated hepatic and skeletal muscle oxidative stress, inflammation and insulin function as well as muscle atrophy in HFD-induced middle-aged obese mice.

並列關鍵字

Borage oil ； Insulin function ； Inflammation ； Oxidative stress ； Muscle atrophy

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