探討GABA烏龍茶萃取物對高脂飲食及恆亮條件誘導小鼠肥胖之改善效果

Abstract

肥胖被認爲是長期熱量之攝取和消耗的不平衡所引起的健康問題，而高脂飲食 (HFD) 和晝夜節律紊亂是導致肥胖的兩個重要因素。最近一份關於能量穩態和生理時鐘的研究指出，晝夜節律紊亂，尤其是恆亮 (LL) 可能會導致體重的增加。GABA烏龍茶萃取物 (OTE) 由GABA烏龍茶經萃取並加以冷凍乾燥所製成，富含咖啡因和GABA，有助於緩解抑鬱和焦慮。然而，OTE對於HFD或LL所誘導肥胖的影響仍不明確。因此，本實驗目的為探討LL是否會誘發肥胖並影響HFD所誘導的肥胖，以及OTE的介入是否可以改善由HFD和/或LL導致的肥胖並探究其潛在機轉。實驗將C57BL/6J小鼠分別介入HFD或處於LL下，使用1% OTE作為處理組。結果顯示，在14周的餵養後，OTE的介入顯著降低了由HFD誘導小鼠的肝臟和各個脂肪的重量。在血清生化分析中，OTE顯著降低了HFD誘導小鼠的血糖和瘦體素含量。此外，OTE還能顯著增強副睪白色脂肪和腹股溝米色脂肪中脂解相關蛋白ATGL表現量和促進HSL磷酸化，且肩胛骨棕色脂肪中產熱相關蛋白UCP-1，PGC-1α和PPARγ表現量也有顯著增加。相比之下，白色脂肪中脂肪生合成相關蛋白AMPK磷酸化顯著增加，且SREBP-1和FASN表現量均被顯著抑制。與HFD組小鼠相比，OTE可以顯著下調肝臟中SREBP-1和FASN的基因和蛋白表現量，以及促進PPARα的基因和蛋白表現量。此外，LL組小鼠體重與ND組相比未呈顯著差異，而LL + HFD則會誘導小鼠肥胖，而OTE的介入對LL或LL + HFD小鼠均未發現顯著改善效果。目前數據表明，LL + HFD沒有影響脂質生合成路徑，但可能通過降低PPARα蛋白表現量來抑制脂肪酸氧化，從而促進肝臟TG的積累。綜上所述，OTE具有潛在的通過增加脂解作用和抑制脂肪生合成達到抗肥胖效果的能力，但對於LL或LL + HFD所導致的肥胖效用甚微。

Obesity is known to be a major public health problem caused by the imbalance of long-term calorie intake and consumption. So far, it is considered that high-fat diet (HFD) and circadian disorder are two of the important factors for obesity. Recent studies link energy homeostasis to the circadian clock at the physiological level, emphasizing that circadian rhythm, especially constant light (LL), may play a significant role in weight gain. GABA oolong tea extracts (OTE), which was extracted and freeze-dried from GABA oolong tea, are rich in caffeine and GABA (Gama-Aminobutyric Acid), and helps with depression and anxiety. However, the effects of OTE on HFD and/or LL-induced obesity is still unclear. Therefore, this study aims to explore whether LL can induce obesity and affect HFD-induced obesity, and whether intervention of OTE can prevent HFD and/or LL-induced obesity and decipher its underlying mechanisms. C57BL/6J mice were fed a HFD or under LL environment, and co-treated with or without 1% OTE during the experiments. The results showed that OTE significantly decreased weights of liver and white adipose tissue in HFD-induced obese mice after 14 weeks treatment. In serum biochemical analysis, OTE decreased the blood glucose and leptin levels compared with HFD group. Furthermore, OTE enhanced lipolysis-related protein expression of ATGL and phosphorylation of HSL in epididymal and inguinal adipose, and thermogenesis-related proteins UCP-1, PGC-1α and PPARγ protein expressions were also increased in scapular brown adipose tissue. In contrast, the phosphorylation of lipogenesis-related proteins AMPK were significantly increased in white adipose tissue by OTE treatment, while SREBP-1 and FASN protein expressions were inhibited in epididymal adipose. Compared to HFD group, OTE significantly down-regulated gene and protein expressions of SREBP-1 and FASN, and promoted gene and protein expressions of PPARα in liver. Besides, LL had no significant effect to those in ND, while LL + HFD can induced obesity in mice, and OTE treatment has no effect on both LL and LL + HFD groups. Current data indicate that LL + HFD may not affect hepatic de novo lipogenesis pathway, but decreased the PPARα protein expression to inhibit fatty acid oxidation, eventually promoted TG accumulation in liver. These results demonstrate that OTE has a potential ability in the application of anti-obesity through enhancing lipolysis and inhibiting lipogenesis, but has little effect on obesity caused by LL or LL + HFD.