Genetic and Microbial Associations to Plasma and Fecal Bile Acids in Obesity Relate to Plasma Lipids and Liver Fat Content

被引：82

作者：

Chen, Lianmin ^{[1
,2
]}

van den Munckhof, Inge Cl ^{[3
,4
]}

Schraa, Kiki ^{[3
,4
]}

ter Horst, Rob ^{[3
,4
]}

Koehorst, Martijn ^{[1
,5
]}

van Faassen, Martijn ^{[5
]}

van der Ley, Claude ^{[5
]}

Doestzada, Marwah ^{[1
,2
]}

Zhernakova, Daria, V ^{[2
,6
]}

Kurilshikov, Alexander ^{[2
]}

Bloks, Vincent W. ^{[1
]}

Groen, Albert K. ^{[1
,5
,7
]}

Riksen, Niels P. ^{[3
,4
]}

Rutten, Joost H. W. ^{[3
,4
]}

Joosten, Leo A. B. ^{[3
,4
,8
]}

Wijmenga, Cisca ^{[9
]}

Zhernakova, Alexandra ^{[2
]}

Netea, Mihai G. ^{[3
,4
,10
,11
]}

Fu, Jingyuan ^{[1
,2
]}

Kuipers, Folkert ^{[1
,5
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, NL-9713 AV Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[3] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6500 HB Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Med Ctr, NL-6500 HB Nijmegen, Netherlands

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, NL-9713 AV Groningen, Netherlands

[6] ITMO Univ, Ctr Comp Technol, Lab Genom Divers, St Petersburg 197101, Russia

[7] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Vasc Med, NL-1012 WX Amsterdam, Netherlands

[8] Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca 400000, Romania

[9] Univ Groningen, NL-9712 CP Groningen, Netherlands

[10] Univ Bonn, Life & Med Sci Inst, Dept Genom & Immunoregulat, D-53113 Bonn, Germany

[11] Craiova Univ Med & Pharm, Human Genom Lab, Craiova 200349, Romania

来源：

CELL REPORTS | 2020年 / 33卷 / 01期

基金：

欧洲研究理事会;

关键词：

HUMANS; HYPERTRIGLYCERIDEMIA; MICE;

D O I：

10.1016/j.celrep.2020.108212

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Bile acids (BAs) are implicated in the etiology of obesity-related conditions such as non-alcoholic fatty liver disease. Differently structured BA species display variable signaling activities via farnesoid X receptor (FXR) and Takeda G protein-coupled BA receptor 1 (TGR5). This study profiles plasma and fecal BAs and plasma 7a-hydroxy-4-cholesten-3-one (C4) in 297 persons with obesity, identifies underlying genetic and microbial determinants, and establishes BA correlations with liver fat and plasma lipid parameters. We identify 27 genetic associations (p < 5 x 10(-8)) and 439 microbial correlations (FDR < 0.05) for 50 BA entities. Additionally, we report 111 correlations between BA and 88 lipid parameters (FDR < 0.05), mainly for C4 reflecting hepatic BA synthesis. Inter-individual variability in the plasma BA profile does not reflect hepatic BA synthetic pathways, but rather transport and metabolism within the enterohepatic circulation. Our study reveals genetic and microbial determinants of BAs in obesity and their relationship to disease-relevant lipid parameters that are important for the design of personalized therapies targeting BA-signaling pathways.

引用

页数：13

共 42 条

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Bile acid composition regulates the manganese transporter Slc30a10 in intestine [J].