- 學位論文
琉璃苣油改善餵食高脂飲食中年小鼠肝臟與脂肪組織中脂肪代謝與胰島素阻抗之功效
Borage oil improves lipid metabolism and insulin resistance in liver and adipose tissue of middle-aged mice fed a high fat diet
摘要
肥胖及老化皆會造成腹部脂肪的累積，而腹部肥胖是很多慢性疾病的重要危險因子；脂肪細胞會因脂質累積過多誘發低度慢性發炎，是胰島素阻抗和非酒精性脂肪肝病的重要病因。琉璃苣油富含gamma-次亞麻油酸(gamma-linolenic acid，GLA)，研究證實GLA具有抗發炎功效。本研究評估補充琉璃苣油改善餵食高脂飲食小鼠白色脂肪組織量、肝臟及脂肪組織中脂質代謝、胰島素阻抗與發炎之功效及相關機制。結果顯示，補充琉璃苣油可顯著降低高脂飲食誘發小鼠血清中膽固醇、三酸甘油酯、丙胺酸轉胺酶、游離脂肪酸及高敏感度C反應蛋白，亦可顯著減少小鼠副睪脂肪重量與細胞大小。在脂肪組織，補充琉璃苣油可能藉由改善Adipokines (即Leptin、Adiponectin)、發炎相關因子[即TNF-α (Tumor Necrosis Factor-α)、IL-1β (Interleukin-1 beta)、IL-6 (Interleukin-6)、Ccl2 (Monocyte Chemoattractant protein-1)、F4/80、TLR4 (Toll-like receptor 4)、NLRP3 (NLR family pyrin domain containing 3)、p-ERK(Thr202/Tyr204)、p-P38(Thr180/Tyr182)、p-IκBα(Ser32.36)及NFκB p-P65(Ser536)]與訊息傳遞路徑[即SIRT-1 (Sirtuin-1)及PGC-1α (Peroxisome proliferator activated receptor γ coactivator-1α)]表現，改善胰島素訊號路徑[即p-PKCθ(Thr538)、p-IRS1(Ser307) (Phosphate-insulin receptor substrate 1)、p-Akt(Ser473)及GLUT4 (Glucose transporter 4)]與脂肪代謝相關因子[即p-HSL(Ser563) (Hormone-sensitive lipase)、SREBP-1c (Sterol regulatory element binding protein-1c)、SREBF1 (Sterol regulatory element-binding transcription factor 1)及CD36 (Cluster of differentiation 36)]表現。此外在肝臟組織，補充琉璃苣油可顯著減少高脂飲食誘發小鼠肝臟中脂質與三酸甘油酯含量以及纖維化表現。補充琉璃苣油可能藉由改善AMPK (AMP-activated protein kinase)與SIRT-1，及發炎相關因子[即p-ERK(Thr202/Tyr204)、p-JNK(Thr183.185)、p-P38(Thr180/Tyr182)及NLRP3]表現，降低脂質與膽固醇合成因子[即FAS (Fatty acid synthase)、L-FABP (L-type fatty acid binding protein)、SREBP-1c、SREBF1及HMGCR (Hydroxymethylglutaryl-CoA reductase)]表現，增加脂肪分解因子[ACO (Acetyl CoA Oxidase)、CPT-1 (Carnitine palmitoyltransferase-1)及PPARα (Peroxisome proliferator activated receptor α)]與纖維化相關因子[即α-SMA (α-Smooth muscle actin)及Collagen type 1]表現。綜和上述結果可知，補充琉璃苣油有助於改善高脂飲食誘導小鼠發炎反應、脂質代謝與胰島素阻抗。
並列摘要
Obesity and aging both lead to the accumulation of abdominal adipose tissue, and abdominal obesity is an important risk factor for many chronic diseases. Adipocytes induce low-grade chronic inflammation due to excessive lipid accumulation which is associated with insulin resistance and nonalcoholic fatty liver disease (NAFLD). Borage oil is rich in gamma-linolenic acid (GLA), which has been shown to have anti-inflammatory effects. This study evaluated the efficacy and related mechanisms of borage oil supplementation in improving white adipose tissue mass, and lipid metabolism, insulin resistance, and inflammation in liver and adipose tissue in mice fed a high-fat diet. The results showed that borage oil supplementation could significantly reduce serum cholesterol, triglyceride, alanine transaminase (ALT), free fatty acids (FFA) and high-sensitivity C-reactive protein (hsCRP) in mice fed a high-fat diet, and also significantly reduce epididymal white adipose tissue weight and cell size in mice. In adipose tissue, borage oil supplementation may improve adipokines (i.e. Leptin, Adiponectin), inflammation-related factors [i.e. Tumor Necrosis Factor-α (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Monocyte Chemoattractant protein-1 (MCP-1/Ccl2), F4/80, Toll-like receptor 4 (TLR4), NLR family pyrin domain containing 3 (NLRP3), p-ERK(Thr202/Tyr204), p-P38(Thr180/Tyr182), p-IκBα(Ser32.36) and NFκB p-P65(Ser536)] and signaling pathways [i.e. Sirtuin-1 (SIRT-1) and Peroxisome proliferator activated receptor γ coactivator-1α(PGC-1α)] expression, improving insulin signaling pathway [i.e. p-PKCθ(Thr538), Phosphate-insulin receptor substrate 1 (p-IRS1(Ser307)), p-Akt(Ser473) and Glucose transporter 4 (GLUT4)] and lipid metabolism related factors [i.e. Hormone-sensitive lipase (p-HSL(Ser563)), Sterol regulatory element binding protein-1c (SREBP-1c) and Sterol regulatory element-binding transcription factor 1 (SREBF1) and Cluster of differentiation 36 (CD36)] expression. In addition, borage oil supplementation significantly reduced lipid, triglyceride content and fibrosis in the liver of mice fed a high-fat diet. Borage oil supplementation may reduce the expression of lipid and cholesterol synthesis factor [i.e. Fatty acid synthase (FAS), L-type fatty acid binding protein (L-FABP), SREBP-1c, SREBF1 and Hydroxyglutaryl-CoA reductase (HMGCR)] expression ,and increased lipid metabolism factors [i.e. Acetyl CoA Oxidase (ACO), Carnitine palmitoyltransferase -1 (CPT-1) and Peroxisome proliferator activated receptor α (PPARα)] and fibrosis-related factors expression by improving the expression of AMP-activated protein kinase (AMPK) and SIRT-1, and inflammation-related factors [i.e. p-ERK(Thr202/Tyr204), p-JNK(Thr183.185), p-P38(Thr180/Tyr182) and NLRP3]. Together, these findings demonstrate that supplementation of borage oil may improve inflammatory response, lipid metabolism and insulin resistance in mice fed a high-fat diet.