研究氧化白藜蘆醇抑制高脂飲食誘導小鼠肥胖的功效及其分子機轉

Abstract

肥胖已經是全球性的健康問題，且有逐年增加的趨勢。肥胖不在只是外觀上的美感問題，它更是危害人類健康的主要因子。肥胖由能量不平衡導致，當攝入的能量大於耗出時即會造成肥胖，若提高能量消耗時即可延緩肥胖的進展。腹股溝脂肪為較容易棕色化的白色脂肪，易受適當刺激後增加UCP1 (uncoupling protein 1)表現量而增加生熱作用提高能量耗出。此外，UCP1 具有基因多樣性，個體會因為帶有不同的對偶基因而對肥胖有不同的耐受性。本實驗利用Oxyresveratrol (OXY) 和Resveratrol (RES) 餵食高脂飲食誘導肥胖的C57BL/6雄性小鼠，分為正常飲食、高脂飲食 (50% energy from fat)、高脂飲食添加0.5% RES、高脂飲食添加0.1% OXY、高脂飲食添加0.5% OXY，各組n=8 ，飼養11周。結果顯示在不影響攝食量的情況下OXY顯著性的降低小鼠體重及體脂肪 (p<0.05)，但不具有劑量效應，且。血清中的ALT和TG也有顯著性的降低，肝臟組織切片顯示餵食RES和OXY皆可以減少油滴累積。進一步利用即時聚合酶鏈式反應和西方墨點法分析其分子機制，結果顯示，餵食OXY可增加Nurf1和CPT1 的基因表現和Sirt1和PGC1α的蛋白質表現量，推測可能增加粒線體的生成的現象。另一方面，餵食OXY可增加UCP1, Cidea, CD137基因表現和棕色化相關的蛋白: PRDM16, PPARα, C/EBPβ而使得UCP1表現增加。同樣地，在IHC也有相同的趨勢。此外，推測餵食OXY得此功效是由MAPK-p38的活化而不是AMPK路徑。綜合以上，推測餵食OXY和RES可藉由提高增加個體的能量消耗的相關蛋白，延緩肥胖的進展。將天然物搭配平日飲食可改變個體形成”易瘦”體質，Oxyresveratrol具有開發成不易形成體脂肪之保健食品的潛力。

Obesity plays an important role on modern people’s health issue, obesity also bring to some disease, like type2 DM, non-alcoholic fatty liver disease (NAFLD). Our study postulated oxyresveratrol (OXY), found on mulberry, have anti-obesity effect by browning white adipose tissue (WAT), elevating uncoupling proteins expression (UCP1) on high-fat diet (50% energy from fat, HFD) animal model . Five-week-old C57BL/6 randomly separated into five groups, normal diet (ND), HFD (50% energy from fat), HFD+0.5% RES (RES), HFD+0.1% OXY (LOXY) and HFD+0.5%OXY (HOXY) for 11 weeks. Compared to HFD group, administrated OXY can siginificantly result in reduce body weight, body fat ratio, serum total triglyceride levels and alanine aminotransferase, without affecting food intake. Treatment with OXY can elevate gene expression of Nurf1 and CPT1 and protein levels of Sirt1 and PGC1α, which are related to mitochondria biogenesis and lipid oxidation. In addition to, treated with OXY significantly increased mRNA and/or protein expression of brown adipocyte markers, including UCP1, PRDM16, Cidea, PGC1α, PPARα and C/EBPβ. The result of IHC showed that treated with OXY increasing UCP1 expressions. These results suggested that an ability of browning adipose could through MAPK-p38 pathway rather than AMPK. To sum up, supplemntion with OXY and RES have similar ability of attenuate HFD fed induced obesity, owning to higher energy expenditure. Overall, our results suggest that OXY has potential to act as thermogenic agent for future applications in the prevention and treatment of metabolic syndrome and obesity.