Dietary fat and gut microbiota interactions determine diet-induced obesity in mice
Open accessAbstract
Objective 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. Methods 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. Results 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. Conclusions In conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.
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- Authors
- Kübeck, R., Bonet-Ripoll, C., Hoffmann, C., Walker, A., Müller, V. M., Schüppel, V. L., Lagkouvardos, I., Scholz, B., Engel, K.-H., Daniel, H., Schmitt-Kopplin, P., Haller, D., Clavel, T., & Klingenspor, M.
- Affiliations
- Else Kröner Fresenius Zentrum für Ernährungsmedizin (DE)
- Helmholtz Munich (DE)
- Technical University of Munich (DE)
- Corresponding author
- Klingenspor, Martin
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 5
- Issue
- 12
- Pages
- 1162-1174
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC5123202
- OpenAlex
- W2530535683
- Cited by
- 211
- References
- 66
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 18 · 2023: 22 · 2022: 32 · 2021: 35 · 2020: 30 · 2019: 19 · 2018: 17 · 2017: 11
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- Funders
- ZIEL – Institute for Food and Health
- Else-Kröner-Fresenius-Stiftung
- German Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- diet-induced obesity, gut microbiota, germ-free mice, dietary cholesterol, lard, palm oil, bile acids, estradiol, energy expenditure, cecal metabolites, hepatic bile acid synthesis, Clostridiales, host-microbe interactions, high-fat diet
- MeSH terms
- Gastrointestinal Microbiome, Adipose Tissue, Animals, Cholesterol, Cholesterol, Dietary, Dietary Fats, Liver, Male, Mice, Inbred C57BL, Obesity, Lipid Metabolism, Mice, Diet, High-Fat
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