Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.
Sanders, Francis WB
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Sanders, F. W., Acharjee, A., Walker, C., Marney, L., Roberts, L. D., Imamura, F., Jenkins, B., et al. (2018). Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.. Genome biology, 19 (1), 79. https://doi.org/10.1186/s13059-018-1439-8
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. Our aims were to investigate whether a sub-set of TAGs were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. Results: We conducted direct infusion mass spectrometry of lipids in plasma to study the association between specific triacylglycerols (TAGs) and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study (n=1507), and evaluated clustering of TAGs in the National Survey of Health and Development UK cohort (n=1701). TAGs formed 3 clusters, with those TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons being specifically associated with hepatic steatosis. These TAGs were 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 was 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 were increased in plasma from patients with biopsy-confirmed steatosis. Conclusion: A sub-set of TAGs are 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.
Liver, Animals, Mice, Inbred C57BL, Humans, Mice, Mice, Obese, Fatty Liver, Carbohydrates, Lipids, Triglycerides, Diet, Risk, Middle Aged, Female, Male, Lipogenesis
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
MEDICAL RESEARCH COUNCIL (MR/L00002/1)
Medical Research Council (MC_EX_MR/L100002/1)
Medical Research Council (MC_PC_13030)
British Heart Foundation (RG/12/13/29853)
Fondazione Umberto Veronesi (unknown)
Embargo Lift Date
External DOI: https://doi.org/10.1186/s13059-018-1439-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277096