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Lack of liver steatosis in germ-free mice following hypercaloric diets

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Abstract

Purpose

Experimental liver steatosis induced by overfeeding is associated with enhanced gut permeability and endotoxin translocation to the liver. We examined the role of the gut microbiota for steatosis formation by performing the feeding experiments in mice raised under conventional and germ-free (GF) housing.

Methods

Adult wild-type and GF mice were fed a Western-style diet (WSD) or a control diet (CD), the latter combined with liquid fructose supplementation (F) or not, for 8 weeks. Markers of liver steatosis and gut permeability were measured after intervention.

Results

Mice fed a WSD increased body weight compared to those fed a CD (p < 0.01) under conventional, but not under GF conditions. Increased liver weight, liver-to-body-weight ratio and hepatic triglycerides observed in both the WSD and the CD + F groups, when compared with the CD group, were not apparent under GF conditions, whereas elevated plasma triglycerides were visible (p < 0.05). Wild-type mice fed a WSD or a CD + F, respectively, had thinner adherent mucus layer compared to those fed a CD (p < 0.01), whereas GF mice had always a thin mucus layer independently of the diet. GF mice fed a CD showed increased plasma levels of FITC-dextran 4000 (1.9-fold, p < 0.05) and intestinal fatty acid-binding protein-2 (2.4-fold, p < 0.05) compared with wild-type mice.

Conclusions

GF housing results in an impaired weight gain and a lack of steatosis following a WSD. Also the fructose-induced steatosis, which is unrelated to body weight changes, is absent in GF mice. Thus, diet-induced experimental liver steatosis depends in multiple ways on intestinal bacteria.

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Acknowledgements

Supported in part by a Grant from the German Research Foundation (BI 424/8-1; to SCB).

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Author notes

  1. Dominik Pretz

    Present address: Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, 9054, New Zealand

Authors and Affiliations

  1. Department of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70593, Stuttgart, Germany

    Valentina Kaden-Volynets, Ulrike Neumann, Dominik Pretz, Andreas Rings & Stephan C. Bischoff

  2. Institute for Laboratory Animal Science, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    Marijana Basic & André Bleich

Authors
  1. Valentina Kaden-Volynets
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  2. Marijana Basic
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  3. Ulrike Neumann
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  4. Dominik Pretz
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  5. Andreas Rings
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  6. André Bleich
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  7. Stephan C. Bischoff
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Contributions

SCB and AB conception and design of the study; SCB funding of the study; VV and MB conduction of the studies, AR, DP, UN and VV acquisition of data; SCB and VV statistical analysis and interpretation of data; AR technical and material support; AB and MB provided the germ-free facility; SCB and VV drafting the manuscript; AB and MB revising the manuscript critically for important intellectual content; SCB had primary responsibility for final content.

Corresponding author

Correspondence to Stephan C. Bischoff.

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The authors declare that they have no conflict of interest.

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Kaden-Volynets, V., Basic, M., Neumann, U. et al. Lack of liver steatosis in germ-free mice following hypercaloric diets. Eur J Nutr 58, 1933–1945 (2019). https://doi.org/10.1007/s00394-018-1748-4

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  • DOI: https://doi.org/10.1007/s00394-018-1748-4

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