Odd chain fatty acid metabolism in mice after a high fat diet


Epidemiological studies show that higher circulating levels of odd chain saturated fatty acids (FA: C15:0 and C17:0) are associated with lower risk of metabolic disease. These odd chain saturated fatty acids (OCSFA) are produced by α-oxidation in peroxisomes, de novo lipogenesis, from the diet and by gut microbiota. Although present at low concentrations, they are of interest as potential targets to reduce metabolic disease risk. To determine whether OCSFA are affected by obesogenic diets, we have investigated whether high dietary fat intake affects the frequency of OCSFA-producing gut microbiota, liver lipid metabolism genes and circulating OCSFA. FA concentrations were determined in liver and serum from pathogen-free SPF C57BL/6 J mice fed either standard chow or a high fat diet (HFD; 60% calories as fat) for four and twelve weeks. Post-mortem mouse livers were analysed histologically for fat deposition by gas chromatography–mass spectrometry for FA composition and by qPCR for the lipid metabolic genes fatty acid desaturase 2 (FADS2), stearoyl CoA desaturase 1 (SCD1), elongation of long-chain fatty acids family member 6 (ELOVL6) and 2-hydroxyacyl-CoA lyase 1 (HACL). Gut microbiota in faecal pellets from the ileum were analysed by 16S RNA sequencing. A significant depletion of serum and liver C15:0 (>50%; P < 0.05) and liver C17:0 (>35%; P < 0.05) was observed in HFD-fed SPF mice in parallel with hepatic fat accumulation after four weeks. In addition, liver gene expression (HACL1, ELOVL6, SCD1 and FADS2) was lower (>50%; P < 0.05) and the relative abundance of beneficial C3:0-producing gut bacteria such as Akkermansia, Lactobacillus, Bifidobacterium was lower after HFD in SPF mice. In summary, high dietary fat intake reduces serum and liver OCSFA, OCSFA-producing gut microbiota and is associated with impaired liver lipid metabolism. Further studies are required to identify whether there is any beneficial effect of OCSFA and C3:0-producing gut bacteria to counter metabolic disease.

Publication DOI: https://doi.org/10.1016/j.biocel.2021.106135
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: (c) 2021, The Author(s). Published by Elsevier Ltd. This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/ ). Funding: HRG and DG acknowledge support from the BBSRC BB/M028100/2 and the Glenn Foundation. OJI acknowledges support from Aston University for a postgraduate scholarship. IA acknowledges the Commonwealth PhD scholarship, GHCS-2016-146 Commonwealth Scholarships Commission, UK, 2016-2019.
Uncontrolled Keywords: Free fatty acids,Gut microbiota,Liver,Odd-chain saturated fatty acids,Steatosis,Biochemistry,Cell Biology
Publication ISSN: 1878-5875
Last Modified: 12 Jun 2024 07:23
Date Deposited: 17 Dec 2021 09:07
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Related URLs: https://linking ... 357272521002168 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2022-02
Published Online Date: 2021-12-10
Accepted Date: 2021-12-07
Authors: Ampong, Isaac
John Ikwuobe, O.
Brown, James Ep (ORCID Profile 0000-0002-3504-7373)
Bailey, Clifford J (ORCID Profile 0000-0002-6998-6811)
Gao, Dan
Gutierrez-merino, Jorge
Griffiths, Helen R



Version: Accepted Version

License: Creative Commons Attribution

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