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

Fabbiano, Salvatore; Suárez-Zamorano, Nicolas; Chevalier, Claire; Lazarević, Vladimir; Kieser, Silas; Rigo, Dorothée; Leo, Stefano; Veyrat-Durebex, Christelle; Gaïa, Nadia; Maresca, Marcello; Merkler, Doron; Gomez de Agüero Tamargo, Maria de la Mercedes; Macpherson, Andrew; Schrenzel, Jacques; Trajkovski, Mirko (2018). Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements. Cell metabolism, 28(6), 907-921.e7. Cell Press 10.1016/j.cmet.2018.08.005

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Gomez de Agüero Tamargo, Maria de la Mercedes and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1550-4131

Publisher:

Cell Press

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

24 Jan 2019 11:39

Last Modified:

24 Jan 2019 11:39

Publisher DOI:

10.1016/j.cmet.2018.08.005

PubMed ID:

30174308

Uncontrolled Keywords:

TLR4 beige fat browning caloric restriction fatty liver gut microbiota innate immunity insulin sensitivity

BORIS DOI:

10.7892/boris.122377

URI:

https://boris.unibe.ch/id/eprint/122377

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