Effects of polyphenol-enriched extracts from tea and berry on obesity and gut microbiota in C57BL/6J mice fed a high-fat diet

Ph.D.As a worldwide epidemic, obesity is usually accompanied by metabolic disorders and chronic low-grade inflammation. Consumption of a high-fat diet is one of the major risk factors causing fat accumulation and obesity. Recently, the gut microbiota in the host has been proven to play a pivotal role in mediating the interaction between the high-fat diet and onset of obesity and metabolic comorbidities. Polyphenol-rich nutraceuticals have attracted increasing attention for their prebiotic activity.The objectives of this thesis research were (i) to study the anti-obesity activity of water extracts and polyphenols extracts of green tea, oolong tea, and black tea, as well as anthocyanin-rich blueberry, cranberry, and mulberry extracts; and (ii) to investigate the underlying mechanisms by which the polyphenol-rich prebiotics possess anti-obesity bioactivity via modulating gut microbiota.The first part of this thesis research was to test the beneficial effects of water extracts of green tea, oolong tea, and black tea on obesity in C57BL/6J mice. Mice were randomly divided into 5 groups, fed either a low-fat diet (LFD), a high-fat diet (HFD) or one of the three high-fat diets supplemented with 1% water extracts of green tea, oolong tea, and black tea. Results showed that the dietary supplementation of three tea water extracts equally improved the glucose tolerance and reduced a HFD-induced gain in weight, hepatic lipids, and white adipose tissues weights. This was accompanied by a significant reduction in plasma lipopolysaccharide (LPS) and a significant increase in the production of short chain fatty acids (SCFAs) in feces. The metagenomic analysis showed that the tea extracts changed the overall composition of gut microbiota and decreased the relative abundance of family Rikenellaceae and Desulfovibrionaceae. In addition, tea water extracts could also change the abundance of key operational taxonomic units (OTUs) including OTU473 (Alistipes), OTU229 (Rikenella), OTU179 (Ruminiclostridium) and OTU264 (Acetatifactor).The second part of this thesis research was to investigate the effects of tea polyphenols on obesity and gut microbiota. Mice were fed high-fat diets with addition of 0.5% polyphenol-rich green tea, oolong tea, and black tea extracts. Results showed that the dietary supplementation of three polyphenol-rich tea extracts significantly reduced HFD-induced body weight gain, energy efficiency, and total white adipose tissues weights. The hepatic lipids were effectively reduced and the fecal output of lipids was markedly increased in mice given the tea polyphenol extracts, accompanied by up-regulation of hepatic peroxisome proliferator-activated receptor α (PPARα). In addition, feeding tea polyphenol extracts alleviated the low-grade inflammation by decreasing tumor necrosis factor alpha (TNF-α) in plasma and down-regulating the gene expression and protein levels of TNF-α and monocyte chemoattractant protein-1 (MCP-1) in the liver. Moreover, the metagenomic analysis showed that polyphenol extracts of green tea, oolong tea, and black tea could change the intestinal microbial structures, composition, and metabolic pathways, in a way of favorably modulating their metabolites with suppressing the production of LPS and promoting the production of SCFAs.The third part of this thesis research was to study the effects of anthocyanin extracts of blueberry, cranberry, and mulberry on obesity and gut microbiota. Mice were fed high-fat diets with supplementation of 1% (a low dose) and 2% (a high dose) of each anthocyanin-rich berry extracts. Feeding blueberry and mulberry anthocyanin extracts at both low and high doses significantly decreased the body weight gain, the total adipose tissue weight, and the liver lipids in HFD-induced obese mice. Feeding only high dose but not low dose of cranberry extract diet reduced the body weights, accompanied by a significant reduction in plasma total cholesterol (TC) and TNF-α. The metagenomic analysis showed that the supplementation of anthocyanin-rich blueberry, cranberry, and mulberry extracts reduced plasma LPS, mainly mediated by reducing the relative abundance of Rikenella and Rikenellaceae. Supplementation of anthocyanin-rich berry extracts into a high-fat diet promoted the growth of Lachnoclostridium, Roseburia, and [Clostridium]_innocuum_group in genus level, leading to a greater production of fecal SCFAs.In summary, polyphenols from either three types of tea or three berries possessed an anti-obesity activity in HFD-induced obese mice, most likely by modulating the gut microbiota via promoting the growth of SCFAs-producing bacteria and inhibiting the growth of LPS-producing bacteria in the intestine.肥胖作為一種全球流行病，通常伴有代謝紊亂與慢性炎症。高脂肪飲食成為造成脂肪堆積與肥胖的主要風險因素之一。研究表明，宿主中的腸道微生物菌群在調節高脂肪飲食與肥胖及代謝併發症之間起關鍵作用。富含多酚的營養素因其益生元特性而受到越來越多的關注。本論文的研究目的是 (i) 研究綠茶、烏龍茶及紅茶中的水提物與茶多酚，以及富含花青素的藍莓、蔓越莓及桑椹提取物的抗肥胖特性；(ii) 探究這些富含多酚的益生元通過調節腸道菌群以緩解肥胖症狀的潛在作用機制。本論文試驗第一部分主要探究綠茶、烏龍茶及紅茶水提物對 C57BL/6J 肥胖小鼠的有益作用。將小鼠隨機分為 5 組，分別餵食低脂飲食 (LFD)、高脂肪飲食 (HFD)或添加 1% 綠茶、烏龍茶及紅茶水提物的高脂飲食。結果表明，三種茶葉水提物均顯著提高其葡萄糖耐受度、降低由高脂飲食所誘導的體重增量，及降低肝臟及白色脂肪組織重量。同時伴隨血漿中脂多糖 (LPS) 的顯著降低及糞便中短鏈脂肪酸 (SCFAs) 的顯著增加。宏基因組分析表明，茶葉水提物均改變腸道微生物菌群的總體結構，且降低 Rikenellaceae 與 Desulfovibrionaceae 的相對豐度。此外，茶葉水提物亦改變最小分類單元 (OTUs) 的豐度，包括 OTU473 (Alistipes)、OTU229 (Rikenella)、OTU179 (Ruminiclostridium) 及 OTU264 (Acetatifactor)。本論文試驗第二部分主要研究茶多酚提取物對肥胖及腸道菌群的影響。將小鼠隨機分為 5 組，分別餵食 LFD 、HFD 或添加 0.5% 富含多酚的绿茶、烏龍茶及紅茶提取物的高脂肪飲食。结果表明，添加三種富含多酚的绿茶、烏龍茶及紅茶提取物，均顯著降低高脂誘導體重增量、能量利用效率及白色脂肪組織重量。且富含多酚的茶葉提取物顯著降低肝臟中的脂質含量，增加糞便中脂質的排出量，並伴隨肝臟中過氧化物酶體增殖物激活受體 α (PPARα) 的上調。此外，茶葉提取物餵食組降低血漿中腫瘤壞死因子-α (TNF-α) 且下調肝臟中 TNF-α 與單細胞趨化蛋白-1（MCP-1），從而緩解炎症反應。宏基因組分析表明，富含多酚的绿茶、烏龍茶及紅茶提取物均可改變腸道菌群的整體結構、組成及代謝途徑，從而調節其代謝產物--抑制 LPS 的產生並促進 SCFAs 的生成。本論文試驗第三部分主要探究富含花青素的藍莓、蔓越莓及桑椹提取物對肥胖及腸道菌群的作用。將小鼠隨機分為 8 組，分別餵食 LFD 、HFD 或添加 1% （低劑量）與 2% （高劑量）的三種漿果提取物的高脂肪飲食。餵食低劑量與高劑量的藍莓與桑椹提取物均顯著降低高脂餵養的肥胖小鼠的體重增量、白色脂肪組織重量及肝臟中脂質含量。但只有高劑量餵食的蔓越莓提取物體現出抗肥胖作用，同時顯著降低血漿中總膽固醇及 TNF-α 含量。宏基因組分析表明，富含花青素的藍莓、蔓越莓及桑椹提取物主要通過降低 Rikenella 與 Rikenellaceae 的相對豐度以降低血漿中 LPS 含量。此外，高脂飲食中添加這些富含花青素的漿果提取物，可增加屬水平Lachnoclostridium，Roseburia 及 [Clostridium]_innocuum_group 的相對豐度，從而導致糞便中 SCFAs 含量增加。綜上，提取自三種茶葉與三種漿果的多酚均對高脂誘導的肥胖小鼠展現出抗肥胖特性，主要是通過調節腸道菌群來實現，即促進產 SCFAs 菌類的生長，且抑制產 LPS 菌類的生長。Liu, Jianhui.Thesis Ph.D. Chinese University of Hong Kong 2019.Includes bibliographical references (leaves 125-142).Abstracts also in Chinese.Title from PDF title page (viewed on 27, November, 2020)