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Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.


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Authors

Sanders, Francis WB 
Acharjee, Animesh 
Walker, Celia 
Marney, Luke 
Roberts, Lee D 

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.

Description

Keywords

De novo lipogenesis, Direct infusion mass spectrometry, Non-alcoholic fatty liver disease, Triacylglycerols, Triglycerides, Animals, Carbohydrates, Diet, Fatty Liver, Female, Humans, Lipids, Lipogenesis, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Middle Aged, Risk, Triglycerides

Is Part Of

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/P01836X/1)
Medical Research Council (MC_UU_12015/5)
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 (MC_UU_12015/1)
MRC (MC_PC_13046)
MRC (Unknown)
MRC (unknown)
Medical Research Council (G0802051)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/2)
Medical Research Council (MR/P011705/1)
Medical Research Council (MC_EX_MR/L100002/1)
Medical Research Council (MC_PC_13030)
British Heart Foundation (None)
Medical Research Council (G0600717)
Medical Research Council (MC_G0802535)
Medical Research Council (G0400192)
Fondazione Umberto Veronesi (unknown)
MRC (MC_UU_00014/2)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)
Medical Research Council (MC_PC_13046)