Sanders, FWB, Acharjee, A, Walker, C et al. (16 more authors) (2018) Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption. Genome Biology, 19. 79. ISSN 1474-760X
Abstract
Background
Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates.
Results
We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16–18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis.
Conclusion
A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
Keywords: | Non-alcoholic fatty liver disease; Direct infusion mass spectrometry; De novo lipogenesis; Triacylglycerols; Triglycerides |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Jun 2018 15:23 |
Last Modified: | 21 Jun 2018 15:23 |
Status: | Published |
Publisher: | BioMed Central |
Identification Number: | 10.1186/s13059-018-1439-8 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:132382 |