Huebbe Patricia, Nikolai Sibylle, Schloesser Anke, Herebian Diran, Campbell Graeme, Glüer Claus-Christian, Zeyner Annette, Demetrowitsch Tobias, Schwarz Karin, Metges Cornelia C, Roeder Thomas, Schultheiss Gerhard, Ipharraguerre Ignacio R, Rimbach Gerald
Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
These authors share the first authorship.
Oncotarget. 2017 May 23;8(43):73501-73515. doi: 10.18632/oncotarget.18113. eCollection 2017 Sep 26.
In this study we addressed the questions whether an Atlantic brown algae extract (BAE) affects diet induced obesity in mice and which would be the primary targets and underlying key mechanisms. Male C57 BL/6 mice were fed a hypercaloric diet, referred to as high fat diet (HFD), supplemented with a freeze-dried aqueous BAE from (5 %) for 8 months. Compared to the control group, dietary BAE supplementation significantly attenuated increase in body weight and fat mass. We observed apparent metabolic improvement including normalization of blood glucose, reduced plasma leptin, reduced fecal bile salt hydrolase activity with lower microbial production of toxic bile acid metabolites in the gut and increased systemic bile acid circulation in BAE-fed mice counteracting adverse effects of long term HFD feeding. Survival of mice receiving dietary BAE supplementation appeared slightly enhanced; however, median and maximal life spans as well as hepatic mTOR activation were not significantly different between BAE and control mice. We suggest that the beneficial metabolic effects of our BAE are at least partly mediated by alterations in gut microbiota associated with fermentation of indigestible polysaccharides that are major components of brown algae such as alginates and fucoidans. We moreover propose a multi-factorial mechanism that involves profound alterations in bile acid homeostasis, changes in intestinal and systemic glucose metabolism likely including increased intestinal gluconeogenesis, increased activity of the intestinally derived hormone GLP-1 contributing to promote systemic insulin sensitivity, and inhibition of α-amylase activity, which expectably limits dietary carbohydrate digestion and glucose release.
在本研究中，我们探讨了大西洋褐藻提取物（BAE）是否会影响小鼠饮食诱导的肥胖，以及其主要靶点和潜在关键机制是什么。雄性C57 BL/6小鼠喂食高热量饮食，即高脂饮食（HFD），并添加5%的冻干BAE水溶液，持续8个月。与对照组相比，饮食中添加BAE显著减轻了体重和脂肪量的增加。我们观察到明显的代谢改善，包括血糖正常化、血浆瘦素降低、粪便胆汁盐水解酶活性降低、肠道中有毒胆汁酸代谢物的微生物产生减少，以及BAE喂养小鼠的全身胆汁酸循环增加，抵消了长期HFD喂养的不利影响。接受饮食BAE补充的小鼠存活率似乎略有提高；然而，BAE小鼠和对照小鼠的中位寿命和最大寿命以及肝脏mTOR激活没有显著差异。我们认为，我们的BAE的有益代谢作用至少部分是由与不可消化多糖发酵相关的肠道微生物群改变介导的，这些不可消化多糖是褐藻的主要成分，如藻酸盐和岩藻聚糖。此外，我们提出了一种多因素机制，该机制涉及胆汁酸稳态的深刻改变、肠道和全身葡萄糖代谢的变化，可能包括肠道糖异生增加、肠道衍生激素GLP-1活性增加，有助于促进全身胰岛素敏感性，以及α-淀粉酶活性的抑制，这有望限制饮食中碳水化合物的消化和葡萄糖释放。
