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肠道微生物群和短链脂肪酸部分介导菊粉对肥胖 ob/ob 小鼠代谢紊乱的有益作用。

Gut microbiota and short chain fatty acids partially mediate the beneficial effects of inulin on metabolic disorders in obese ob/ob mice.

机构信息

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Research Department, The Rocket Force Characteristic Medical Center of Chinese People's Liberation Army, Beijing, China.

出版信息

J Food Biochem. 2022 May;46(5):e14063. doi: 10.1111/jfbc.14063. Epub 2022 Feb 7.

DOI:10.1111/jfbc.14063
PMID:35128673
Abstract

Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. Obese ob/ob mice were fed a standard chow, a low fiber diet (LFD) or a high fiber diet (HFD) for 4 weeks, and the body weight, fecal short chain fatty acids (SCFAs) level, and plasma and liver lipid profiles were analyzed. Oral glucose tolerance testing, and gut microbiota sequencing were also conducted. Dietary inulin improved the dysbiosis of the gut microbiota, attenuated the decrease in phylum Bacteroidetes, repressed the increase of phylum Firmicutes, and led to an increase in the ratio of Firmicutes/Bacteroidetes. At the family level, inulin promoted the expansion of SCFAs-producing Ruminococcaceae and Lachnospiraceae bacteria, which increased the fecal SCFAs concentrations. At the genus level, inulin increased the levels of Bacteroides and Bifidobacteria. Furthermore, our results revealed that there was enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which might be induced by the higher production of SCFAs, and this may underlie the improvements in the disorders of glucose and lipid metabolism seen in mice with added dietary inulin. In conclusion, inulin may ameliorate metabolic disorders by remodeling the gut microbiota and increasing the production of SCFAs, which might be mediated by the ANGPTL4-related signaling pathway. Interventions targeting the gut microbiota warrant further investigation as a novel therapy for metabolic diseases. PRACTICAL APPLICATIONS: Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. In the present study, we investigated the effects of dietary fiber (inulin) on metabolic homeostasis using ob/ob mice. The results of our study demonstrate that inulin-induced remodeling of the gut microbiota resulted in increased production of short chain fatty acids (SCFAs), leading to the enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which improved the glucose and lipid metabolism. Our results suggest that the gut microbiota, SCFAs and ANGPTL4 pathway at least partially mediate the beneficial effects of inulin on metabolic disorders in ob/ob mice.

摘要

越来越多的证据表明,肥胖和代谢紊乱与肠道微生物群落的失调有关。膳食菊粉有利于调节这种失调,代表了改善葡萄糖和脂质代谢紊乱的一种潜在手段。然而,这些改善的机制在很大程度上尚不清楚。肥胖 ob/ob 小鼠喂食标准饲料、低纤维饮食(LFD)或高纤维饮食(HFD)4 周,分析体重、粪便短链脂肪酸(SCFA)水平以及血浆和肝脏脂质谱。还进行了口服葡萄糖耐量试验和肠道微生物组测序。膳食菊粉改善了肠道微生物群落的失调,减弱了门 Bacteroidetes 的减少,抑制了门 Firmicutes 的增加,并导致 Firmicutes/Bacteroidetes 比值增加。在科水平上,菊粉促进了产生 SCFA 的 Ruminococcaceae 和 Lachnospiraceae 细菌的扩张,增加了粪便 SCFA 浓度。在属水平上,菊粉增加了 Bacteroides 和 Bifidobacterium 的水平。此外,我们的结果表明,血管生成素样蛋白 4(ANGPTL4)的表达增强,这可能是由 SCFA 产量增加引起的,这可能是添加膳食菊粉的小鼠葡萄糖和脂质代谢紊乱改善的基础。总之,菊粉可能通过重塑肠道微生物群和增加 SCFA 的产生来改善代谢紊乱,这可能是通过 ANGPTL4 相关信号通路介导的。针对肠道微生物群的干预措施作为代谢疾病的一种新疗法值得进一步研究。实际应用:越来越多的证据表明,肥胖和代谢紊乱与肠道微生物群落的失调有关。膳食菊粉有利于调节这种失调,代表了改善葡萄糖和脂质代谢紊乱的一种潜在手段。然而,这些改善的机制在很大程度上尚不清楚。在本研究中,我们使用 ob/ob 小鼠研究了膳食纤维(菊粉)对代谢平衡的影响。我们的研究结果表明,菊粉诱导的肠道微生物群重组成纤维相关代谢物(SCFA)的产生增加,导致血管生成素样蛋白 4(ANGPTL4)的表达增强,改善了葡萄糖和脂质代谢。我们的结果表明,肠道微生物群、SCFA 和 ANGPTL4 途径至少部分介导了菊粉对 ob/ob 小鼠代谢紊乱的有益作用。

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