Common gut microbial metabolites of dietary flavonoids exert potent protective activities in β-cells and skeletal muscle cells.
Common gut microbial metabolites of dietary flavonoids exert potent protective activities in β-cells and skeletal muscle cells.
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DOI：
10.1016/j.jnutbio.2018.09.004
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Neilson AP
中科院分区：
文献类型：
--
作者：
Bitner BF;Ray JD;Kener KB;Herring JA;Tueller JA;Johnson DK;Tellez Freitas CM;Fausnacht DW;Allen ME;Thomson AH;Weber KS;McMillan RP;Hulver MW;Brown DA;Tessem JS;Neilson AP
黄酮类化合物是具有潜在抗糖尿病活性的膳食化合物。许多类黄酮的生物利用度很差，因此循环浓度很低。未吸收的黄酮类化合物被肠道微生物群代谢为较小的代谢物，这些代谢物比其前体更具生物利用度。这些代谢产物的活性可能是类黄酮与健康之间联系的部分原因。然而，人们对这些活动仍然知之甚少。我们研究了类黄酮微生物代谢物[马尿酸（HA）、高香草酸（HVA）和5-苯基戊酸（5 PVA）]在原代骨骼肌和β细胞中的生物活性，并与天然类黄酮（[（−）-表儿茶素，EC]）进行了比较。在肌肉中，EC是葡萄糖氧化的最有效刺激剂，而5 PVA和HA在25 μM时模拟葡萄糖代谢，并且所有化合物在损伤后保留线粒体功能。然而，EC和代谢产物不能解偶联线粒体呼吸，除了10 μM的5 PVA。在β-细胞中，与EC相比，所有代谢产物均更有效地增强葡萄糖刺激的胰岛素分泌（GSIS）。与EC不同，代谢物似乎增强GSIS而不增强β细胞线粒体呼吸或增加线粒体电子传递链组分的表达，并且对β细胞胰岛素含量具有不同的影响。本结果证明了类黄酮微生物代谢物对于保存β细胞功能和葡萄糖利用的活性。此外，我们的数据表明，代谢产物和天然化合物可能通过不同的机制发挥作用，这表明在体内的互补和协同活性，值得进一步研究。这提出了一个有趣的前景，即天然膳食类黄酮的生物利用度可能不像以前认为的那样是生物活性的关键限制因素。
Flavonoids are dietary compounds with potential anti-diabetes activities. Many flavonoids have poor bioavailability and thus low circulating concentrations. Unabsorbed flavonoids are metabolized by the gut microbiota to smaller metabolites, which are more bioavailable than their precursors. The activities of these metabolites may be partly responsible for associations between flavonoids and health. However, these activities remain poorly understood. We investigated bioactivities of flavonoid microbial metabolites [hippuric acid (HA), homovanillic acid (HVA), and 5-phenylvaleric acid (5PVA)] in primary skeletal muscle and β-cells compared to a native flavonoid ([(−)-epicatechin, EC]. In muscle, EC was the most potent stimulator of glucose oxidation, while 5PVA and HA simulated glucose metabolism at 25 μM, and all compounds preserved mitochondrial function after insult. However, EC and the metabolites did not uncouple mitochonndrial respiration, with the exception of 5PVA at10 μM. In β-cells, all metabolites more potently enhanced glucose-stimulated insulin secretion (GSIS) compared to EC. Unlike EC, the metabolites appear to enhance GSIS without enhancing β-cell mitochondrial respiration or increasing expression of mitochondrial electron transport chain components, and with varying effects on β-cell insulin content. The present results demonstrate the activities of flavonoid microbial metabolites for preservation of β-cell function and glucose utilization. Additionally, our data suggest that metabolites and native compounds may act by distinct mechanisms, suggesting complementary and synergistic activities in vivo which warrant further investigation. This raises the intriguing prospect that bioavailability of native dietary flavonoids may not be as critical of a limiting factor to bioactivity as previously thought.
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影响因子：
4.3
作者：
Draney C;Hobson AE;Grover SG;Jack BO;Tessem JS
通讯作者：
Tessem JS
影响因子：
6.1
作者：
Gu Y;Hurst WJ;Stuart DA;Lambert JD
通讯作者：
Lambert JD
影响因子：
7.7
作者：
García-Ocaña, A;Vasavada, RC;Stewart, AF
通讯作者：
Stewart, AF
DOI：
10.1016/j.jnutbio.2015.02.007
发表时间：
2015-08
期刊：
The Journal of nutritional biochemistry
影响因子：
--
作者：
Bitzer ZT;Glisan SL;Dorenkott MR;Goodrich KM;Ye L;O'Keefe SF;Lambert JD;Neilson AP
通讯作者：
Neilson AP
影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell