錐尖擬紅翎藻抑制高脂飲食誘導小鼠肥胖之分子機制

Abstract

肥胖人口於開發中及已開發國家與日俱增，因而使相關代謝疾病發生率居高不下。然而，臨床研究結果顯示，亞洲國家如韓國、日本等地的人口罹患代謝症候群機率遠低於西方國家，進而發現其餐桌飲食普遍存在著多種藻類。其中，數種紅藻具有豐富的活性成分，且對於抗肥胖及相關代謝疾病極具潛力。因此，本研究樣品為錐尖擬紅翎藻 (Agardhiella subulata, AS)，屬紅藻門 (Rhodophyta)，含有豐富的生物活性成分，多醣類、必需胺基酸、礦物質、蝦紅素、不飽和脂肪酸及低的熱量密度。錐尖擬紅翎藻目前為台灣東部沿岸居民、日本的食用海藻，但還未被探討過其是否能減緩肥胖的發生。本次實驗將 4 周齡 C57BL/6 小鼠分為四個組別，正常飲食組 (ND)；高脂飲食組 (50% fat，HFD)；高脂飲食組混合低劑量紅藻粉末 (2% AS，ASL)；高脂飲食組混合高劑量紅藻粉末 (10% AS，ASH)。實驗中飲食及飲水皆為自由攝食，為期13周。13周犧牲後，與HFD組別相比，紅藻組別在不改變攝食量的情況下，皆顯著減緩高脂飲食誘導肥胖小鼠之體重，切片結果則顯示體重的降低可能來自於抑制了肝臟及內臟脂肪的蓄積，且紅藻也能夠改善高脂飲食所誘導血脂紊亂的問題。糞便分析結果顯示，與 HFD 組相比，ASH 組具有代謝多餘三酸甘油酯的效果。進一步探討體內之分子機制，發現紅藻組別顯著提高脂解作用及脂肪酸 β-氧化的作用，顯示促進游離脂肪酸的利用而使血液中 NEFA 的含量降低。另外，紅藻具有提高 Pref1、SOX9 的蛋白表現量而抑制脂肪細胞的新生，並發現可能含有 PPARγ 激動劑的存在而提升血液中 adiponectin 的濃度進而調節血糖。綜合上述結果，紅藻除了增加油脂的排出，還具有抑制脂肪細胞的新生及提升能量代謝的作用而減少脂質於體內的堆積，因此具有減緩肥胖發生的潛力。

An increase of obesity is not only in developed countries but also in developing nations making high prevalence rate of related metabolic diseases. However, incidence of cardiovascular and metabolic disorders was relatively low in Korea, Japan relative to Western countries. Meanwhile, study found that red algae contain variety of bioactive components and have great potential for anti-obesity and related metabolic diseases among several algae that are frequently consumed by Asian populations. In this study, the red seaweed Agardhiella subulata, rich in bioactive components including polysaccharide, essential amino acid, minerals, astaxanthin, unsaturated fatty acid with low overall energy content for whole seaweed was used. Regular consumption of AS in Japan and northern Taiwan but their anti-obesity activity remains unexplored. Four-week-old C57BL/6 mice were used as the experimental animals. Mice were divided into four groups: (1) normal diet group (ND); (2) high-fat diet group (50% fat, HFD); (3) HFD with low dose of AS diet group (2% AS, ASL); (4) HFD with high dose of AS diet group (10% AS, ASH). All groups were fed the experimental diets and drinking water ad libitum for 13 weeks. After 13 weeks of AS supplementation, significantly reduced HFD-induced body weight without altering the amount of food intake. The results of the H&E stain showed that it may be derived from inhibiting the accumulation of lipids in the liver and visceral fat. AS supplementation also improved the lipid profile compared to HFD group. In addition, fecal triglyceride excretion was significantly higher in mice fed 10% AS group. Moreover, we found that AS feeding induce lipolysis and fatty acid β-oxidation which associated with the lower concentration of NEFA compared to HFD group. Also, AS could alleviated hyperplasia through upregulating protein expression of Pref1 and SOX9. Interestingly, higher protein level of PPARγ in AS group, so we guess PPARγ agonist that include in and elevate adiponectin level to improve blood glucose. The results of the current study suggest that AS supplementation not only increasing lipid excretion, but improving energy metabolism and adipogenesis to prevent obesity in high-fat diet fed mice.