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Effect of microbial status on hepatic odd-chain fatty acids is diet-dependent

  • Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF >Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF > SIH > CONV), while cecal propionate showed a negative correlation with hepatic OCFA. On HFI, OCFA levels were highest in SIH and positively correlated with cecal propionate. The propionate content in the CHOW diet was 10 times higher than that of HFI. We conclude that bacterial propionate production affects hepatic OCFA formation, unless this effect is masked by dietary propionate intake.show moreshow less

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Author details:Karolin WeitkunatORCiDGND, Christopher Allen BishopORCiDGND, Maria Wittmüss, Tina Machate, Tina Schifelbein, Matthias Bernd SchulzeORCiDGND, Susanne KlausORCiDGND
DOI:https://doi.org/10.3390/nu13051546
ISSN:2072-6643
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/34064336
Title of parent work (English):Nutrients / Molecular Diversity Preservation International (MDPI)
Publisher:MDPI
Place of publishing:Basel
Publication type:Article
Language:English
Date of first publication:2021/05/04
Publication year:2021
Release date:2023/09/06
Tag:acetate; fatty acid synthesis; gut microbiota; heptadecanoic acid (C17:0); inulin; pentadecanoic acid (C15:0); prebiotics; probiotics; propionate; type-2-diabetes
Volume:13
Issue:5
Article number:1546
Number of pages:15
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
DDC classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Peer review:Referiert
Publishing method:Open Access / Gold Open-Access
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License (German):License LogoCC-BY - Namensnennung 4.0 International
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