Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements

被引：214

作者：

Fabbiano, Salvatore ^{[1
,2
]}

Suarez-Zamorano, Nicolas ^{[1
,2
]}

Chevalier, Claire ^{[1
,2
]}

Lazarevic, Vladimir ^{[3
]}

Kieser, Silas ^{[1
,2
]}

Rigo, Dorothee ^{[1
,2
]}

Leo, Stefano ^{[3
]}

Veyrat-Durebex, Christelle ^{[1
,2
]}

Gaia, Nadia ^{[3
]}

Maresca, Marcello ^{[4
]}

Merkler, Doron ^{[5
]}

de Aguero, Mercedes Gomez ^{[6
]}

Macpherson, Andrew ^{[6
]}

Schrenzel, Jacques ^{[3
]}

Trajkovski, Mirko ^{[1
,2
,7
]}

机构：

[1] Univ Geneva, Dept Cell Physiol & Metab, Ctr Med Univ, Fac Med, CH-1211 Geneva, Switzerland

[2] Univ Geneva, Ctr Diabet, Fac Med, CH-1211 Geneva, Switzerland

[3] Geneva Univ Hosp, Div Infect Dis, Genom Res Lab, CH-1211 Geneva, Switzerland

[4] AstraZeneca Gothenburg, Discovery Biol, Discovery Sci, IMED Biotech Unit, S-43183 Molndal, Sweden

[5] Univ Geneva, Dept Pathol & Immunol, Ctr Med Univ, Fac Med, CH-1211 Geneva, Switzerland

[6] Univ Bern, Maurice Muller Labs DKF, Univ Klin Viszerale Chirurg & Med Inselspital, CH-3010 Bern, Switzerland

[7] Univ Geneva, Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland

来源：

CELL METABOLISM | 2018年 / 28卷 / 06期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

ALTERNATIVELY ACTIVATED MACROPHAGES; WHITE ADIPOSE-TISSUE; INSULIN-RESISTANCE; OBESITY; INFLAMMATION; CATECHOLAMINES; THERMOGENESIS; SEQUENCES; DEPLETION; PRODUCE;

D O I：

10.1016/j.cmet.2018.08.005

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：

Caloric restriction (CR) stimulates development of functional beige fat and extends healthy lifespan. Here we show that compositional and functional changes in the gut microbiota contribute to a number of CR-induced metabolic improvements and promote fat browning. Mechanistically, these effects are linked to a lower expression of the key bacterial enzymes necessary for the lipid A biosynthesis, a critical lipopolysaccharide (LPS) building component. The decreased LPS dictates the tone of the innate immune response during CR, leading to increased eosinophil infiltration and anti-inflammatory macrophage polarization in fat of the CR animals. Genetic and pharmacological suppression of the LPS-TLR4 pathway or transplantation with Tlr4(-/-) bone-marrow-derived hematopoietic cells increases beige fat development and ameliorates diet-induced fatty liver, while Tlr4(-/- )or microbiota-depleted mice are resistant to further CR-stimulated metabolic alterations. These data reveal signals critical for our understanding of the microbiota-fat signaling axis during CR and provide potential new anti-obesity therapeutics.

引用

页码：907 / +

页数：22

共 61 条

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