青絲藻多醣透過調升脂聯素與調節腸道菌相抑制高脂飲食誘導小鼠肥胖之功效

Abstract

在高脂飲食中，不僅僅是導致全身性低度發炎反應亦代謝性內毒素血症 (metabolic endotoxemia)，影響腸道菌群組成進而可能加劇肥胖之形成。近期研究表示，硫化多醣 (Sulphated polysaccharide) 可通過改善腸道菌群，減少代謝異常並維持腸道上皮細胞的完整性來預防高脂飲食誘導的肥胖。然而，青絲藻中 (Ulva prolifera) 的硫化多醣對於延緩肥胖和代謝疾病的機制仍尚未有更進一步的研究。因此，本研究將製備青絲藻多醣並針對高脂飲食誘導小鼠所造成之脂質蓄積、代謝異常及腸道菌群變化進行深入的探討。小鼠飼養期間將利用管餵的方式介入青絲藻多醣 (100，300，500 mg/kg) 並持續15周。結果顯示，青絲藻多醣具延緩小鼠肥胖和改善代謝異常的效果，其中包括粥狀動脈硬化指標 (atherogenic index) 的下降，顯示青絲藻多醣有降低高脂飲食所誘導的心血管疾病發生。蘇木精-伊紅染色結果發現，青絲藻多醣減緩肝臟中脂肪浸潤和脂肪細胞肥大之情形。另外，分別在小鼠的血液、肝臟及脂肪組織中所測得的細胞激素濃度也有下降的趨勢，顯示經由青絲藻多醣的介入後可減少全身性低度發炎反應。從西方墨點法的結果發現，青絲藻多醣可能通過增加脂聯素活性並提高了AMPK的表現量。 有趣的是，由於CPT-1和PPAR 表現量同时升高，青絲藻多醣可能透過PPAR 激动剂增强了-氧化，以達到減脂的效果。 此外，青絲藻多醣也改善了肥胖小鼠中的腸道菌群，其中發現經由青絲藻多醣介入後增加Parasutterella、Feacalibaculum 和 Bifidobacterium，同時減少了Acetatifactor、 Tyzerella、 Ruminococcus 1和Desulfovibrio的豐富度，而菌群的變化可能具有改善肥胖和代謝異常的效果。綜合上述，青絲藻多醣可以減緩高脂飲食誘導的小鼠肥胖及相關代謝疾病之效果，且可能可以營造出一個更健康的腸道環境並有利於益生菌的生長。

Obesity is characterized by low-grade inflammation and accompanying an altered and less diverse gut microbiota composition during a fat-enriched diet. Recently studies indicate that sulphated polysaccharide prevents high-fat diet induced obesity, reduces metabolic disorder, and restores the gut microbiota. However, Ulva prolifera polysaccharide may induce anti-obesogenic effects that have not been examined. Therefore, the present study investigates the possibility of UPP extraction that may prevent diet-induced obesity and metabolic disorder and modulating gut microbiota composition. High-fat diet (HFD)-fed mice are treated with UPP (100, 300, 500mg/kg) by intragastric gavage for 15 weeks. The effects of polysaccharide will be assessed by western blot to determine the lipid metabolism pathway and 16S rDNA-based microbiota analysis to identify the gut bacteria enriched by UPP. The results showed that UPP considerably slowed down the HFD-induced weight gain and improved metabolic disorders in HFD-fed mice. Notably, the effects were associated with reduced adipose tissue hypertrophy, triglyceride concentration in liver and systemic low-grade inflammation, and improved fasting blood glucose. Moreover, our result reveals that UPP may elevate the expression of AMPK via adiponectin activation . Interestingly, we found that UPP may induce PPAR-alpha agonist to enhance beta-oxidation since the elevation of CPT-1 and PPAR-alpha expression simultaneously. Meanwhile, gut microbiota analysis revealed UPP promoted the growth of Parasutterella, Feacalibaculum, and Bifidobacterium, and reduced the abundance of Acetatifactor, Tyzerella, Ruminococcus_1, and Desulfovibrio. The changes in microbiota may have a positively correlated effect on improving obesity and metabolic abnormalities. In summary, UPP may prevent the effects of HFD-induced obesity and the associated metabolic diseases, and may modulate the composition of gut microbiota to facilitate the growth of probiotic.