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PMID: 27900259 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Dietary fat and gut microbiota interactions determine diet-induced obesity in mice.

Molecular metabolism ·Vol. 5 ·No. 12 ·2016-00-00 ·Pages 1162-1174

Kübeck R, Bonet-Ripoll C, Hoffmann C, Walker A, Müller VM, Schüppel VL, Lagkouvardos I, Scholz B, Engel KH, Daniel H, Schmitt-Kopplin P, Haller D, Clavel T, Klingenspor M

Abstract

Gut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. GF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing. GF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes) as a characteristic feature of normal SPF mice fed lard. In conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.

Keywords
ANOVA analysis of variance Abcg5 ATP-binding cassette sub-family G member 5 Abcg8 ATP-binding cassette sub-family G member 8 Actb beta actin Akr1d1 aldo-keto-reductase family member 1 BMR basal metabolic rate CA cholic acid CD control diet CDCA chenodeoxycholic acid CIDEA cell death inducing DFFA-like effector COX4 cytochrome c oxidase subunit 4 Cyp27a1 cholesterol 27 alpha-hydroxylase Cyp7a1 cholesterol 7 alpha-hydroxylase DCA deoxycholic acid DEE daily energy expenditure DIO diet-induced obesity Dhcr7 7-dehydrocholesterol reductase Diet-induced obesity resistance Eef2 eukaryotic elongation factor 2 Energy balance FT-ICR-MS Fourier transform-Ion Cyclotron Resonance-Mass Spectrometry FT-IR Fourier transform-infrared spectroscopy GF germfree GUSB beta-glucuronidase Germfree HDCA hyodeoxycholic acid HP heat production High-fat diet Hmgcr 3-hydroxy-3-methylglutaryl Coenzyme A reductase Hmgcs 3-hydroxy-3-methylglutaryl Coenzyme A synthase 1 Hprt1 hypoxanthine guanine phosphoribosyl transferase Hsd11b1 hydroxysteroid (11-β) dehydrogenase 1 Hsp90 heat shock protein 90 LHFD high-fat diet based on lard Ldlr low density lipoprotein receptor MCA muricholic acid Nr1h2 nuclear receptor subfamily 1 group H member 2 (liver X receptor β) Nr1h3 nuclear receptor subfamily 1 group H member 3 (liver X receptor α) Nr1h4 nuclear receptor subfamily 1 group H member 4 (farnesoid X receptor α) PHFD high-fat diet based on palm oil PRDM16 PR domain containing 16 SPF specific pathogen free Srebf1 sterol regulatory element binding transcription factor 1 TCA taurocholic acid TMCA Tauromuricholic acid Tf2b transcription factor II B UCP1 uncoupling protein 1 UDCA ursodeoxycholic acid UPLC-TOF-MS ultraperformance liquid chromatography-time of flight-mass spectrometry qPCR quantitative real-time polymerase chain reaction
MeSH Terms
Adipose Tissue/metabolism Animals Cholesterol/metabolism Cholesterol, Dietary/metabolism Diet, High-Fat/adverse effects Dietary Fats/adverse effects,metabolism Gastrointestinal Microbiome/physiology Lipid Metabolism/genetics Liver/metabolism Male Mice Mice, Inbred C57BL Obesity/metabolism
Chemicals
Cholesterol, Dietary Dietary Fats Cholesterol
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Kübeck Raphaela
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Molecular Nutritional Medicine, Technical University of Munich, TUM School of Life Sciences Weihenstephan, EKFZ - Else Kröner-Fresenius-Center for Nutritional Medicine, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Bonet-Ripoll Catalina
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Molecular Nutritional Medicine, Technical University of Munich, TUM School of Life Sciences Weihenstephan, EKFZ - Else Kröner-Fresenius-Center for Nutritional Medicine, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Hoffmann Christina
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Molecular Nutritional Medicine, Technical University of Munich, TUM School of Life Sciences Weihenstephan, EKFZ - Else Kröner-Fresenius-Center for Nutritional Medicine, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Walker Alesia
Research Unit Analytical BioGeoChemistry, Department of Environmental Sciences, Helmholtz Zentrum München, Ingolstädter Landstr.1, 85764 Neuherberg, Germany.
Müller Veronika Maria
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Nutritional Physiology, Technical University of Munich, TUM School of Life Sciences Weihenstephan, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Schüppel Valentina Luise
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Nutrition and Immunology, Technical University of Munich, TUM School of Life Sciences Weihenstephan, Maximus-von-Imhof-Forum 2, 85354 Freising, Germany.
Lagkouvardos Ilias
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Scholz Birgit
Chair of General Food Technology, Technische Universität München, Alte Akademie 10, 85354 Freising, Germany.
Engel Karl-Heinz
Chair of General Food Technology, Technische Universität München, Alte Akademie 10, 85354 Freising, Germany.
Daniel Hannelore
Chair of Nutritional Physiology, Technical University of Munich, TUM School of Life Sciences Weihenstephan, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Schmitt-Kopplin Philippe
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Research Unit Analytical BioGeoChemistry, Department of Environmental Sciences, Helmholtz Zentrum München, Ingolstädter Landstr.1, 85764 Neuherberg, Germany; Chair of Analytical Food Chemistry, Technische Universität München, Alte Akademie 10, 85354 Freising, Germany.
Haller Dirk
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Nutrition and Immunology, Technical University of Munich, TUM School of Life Sciences Weihenstephan, Maximus-von-Imhof-Forum 2, 85354 Freising, Germany.
Clavel Thomas
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany.
Klingenspor Martin
ZIEL - Institute for Food and Health, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, Germany; Chair of Molecular Nutritional Medicine, Technical University of Munich, TUM School of Life Sciences Weihenstephan, EKFZ - Else Kröner-Fresenius-Center for Nutritional Medicine, Gregor-Mendel-Str. 2, 85354 Freising, Germany. Electronic address: mk@tum.de.
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Article Info
Journal
Molecular metabolism
Abbr.
Mol Metab
ISSN
2212-8778
DOI
10.1016/j.molmet.2016.10.001
Email
mk@tum.de
Published
2016-00-00
Epub
2016-00-13
Pages
1162-1174
Language
English
Region
Germany
NLM ID
101605730
PMCID
PMC5123202
Subset
IM
External Links
PubMed source DOI: 10.1016/j.molmet.2016.10.001 PMC Full Text View journal details
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