Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects.
Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects.
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DOI：
10.1038/s41424-018-0025-4
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发表时间：
2018-05-25
影响因子：
3.6
通讯作者：
Nieuwdorp M
中科院分区：
文献类型：
--
作者：
Bouter K;Bakker GJ;Levin E;Hartstra AV;Kootte RS;Udayappan SD;Katiraei S;Bahler L;Gilijamse PW;Tremaroli V;Stahlman M;Holleman F;van Riel NAW;Verberne HJ;Romijn JA;Dallinga-Thie GM;Serlie MJ;Ackermans MT;Kemper EM;Willems van Dijk K;Backhed F;Groen AK;Nieuwdorp M
肠道微生物来源的短链脂肪酸（SCFA）与有益的代谢作用有关。然而，从未研究过口服丁酸盐对人体代谢参数的直接影响。因此，在这项首次在男性中进行的初步研究中，我们用口服丁酸钠治疗了消瘦和代谢综合征男性受试者，并研究了对代谢的影响。健康瘦男性（n = 9）和代谢综合征男性（n = 10）每天口服4 g丁酸钠，持续4周。在治疗前后，通过使用[6，6 - 2 H2]-葡萄糖的两步高胰岛素正葡萄糖钳夹测定胰岛素敏感性。使用18F-FDG PET-CT观察棕色脂肪组织（BAT）对葡萄糖的摄取。在治疗前后测定粪便SCFA和胆汁酸浓度以及微生物群组成。口服丁酸盐对治疗后的血浆和粪便丁酸盐水平没有影响，但确实改变了血浆和粪便中的其他SCFA。此外，仅在健康瘦型受试者中观察到外周（中位Rd：从71至82 µmol/kg min，p < 0.05）和肝脏胰岛素敏感性（EGP抑制从75%至82% p < 0.05）的显著改善。尽管基线时瘦型患者的BAT活性（SUVmax：12.4 ± 1.8）显著高于代谢综合征患者（SUVmax：0.3 ± 0.8，p < 0.01），但在两组中均未观察到丁酸盐治疗对BAT的显著影响（瘦型患者的SUVmax为13.3 ± 2.4，代谢综合征患者为1.2 ± 4.1）。口服丁酸盐治疗有益地影响瘦而非代谢综合征受试者的葡萄糖代谢，这可能是由于胰岛素抵抗受试者中SCFA处理的改变。虽然是初步的，但这些首次在男性中的发现反对口服丁酸补充剂作为2型糖尿病患者血糖调节的治疗。
Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 µmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus.
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