Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.
Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.
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DOI：
10.1186/s13059-018-1439-8
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发表时间：
2018-06-20
期刊：
影响因子：
12.3
通讯作者：
Griffin JL
中科院分区：
文献类型：
--
作者：
Sanders FWB;Acharjee A;Walker C;Marney L;Roberts LD;Imamura F;Jenkins B;Case J;Ray S;Virtue S;Vidal-Puig A;Kuh D;Hardy R;Allison M;Forouhi N;Murray AJ;Wareham N;Vacca M;Koulman A;Griffin JL
饮食是代谢性疾病风险的主要因素，但对于非酒精性脂肪肝等疾病的发病率增加是否源于饱和脂肪或游离糖的消费存在争议。在这里，我们调查是否一个子集的三酰甘油（TAG）与肝脂肪变性，以及它们是否从从头脂肪生成（DNL）从消耗的碳水化合物。我们对血浆中的脂质进行直接输注质谱分析，以研究特定TAG与来自英国Fenland研究的志愿者的超声和脂肪肝指数评估的肝脂肪变性之间的关联，并评估英国国家健康与发展调查队列中TAG的聚类。我们发现含有16-18个碳的饱和和单不饱和脂肪酸的TAG与肝脂肪变性特异性相关。这些TAG还与碳水化合物和饱和脂肪的高消耗、肝脂肪变性以及蛋白磷酸酶1调节亚基3b（PPP 1 R3 B）基因的变异相关，PPP 1 R3 B部分调节糖原合成。DNL是在过度吞噬ob/ob小鼠、西方饮食（高脂肪和游离糖）的小鼠和健康人中在高碳水化合物膳食后使用稳定同位素技术测量的，证明DNL的速率与该TAG簇的合成增加相关。此外，这些TAG在来自活检证实的脂肪变性患者的血浆中增加。TAG的一个子集与肝脂肪变性相关，即使在校正常见混杂因素时也是如此。我们认为，西方人群中肝脂肪变性的风险部分是由富含碳水化合物的膳食后DNL增加以及饱和脂肪的消耗所驱动的。本文的在线版本（10.1186/s13059-018-1439-8）包含补充材料，可供授权用户使用。
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. 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. 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. The online version of this article (10.1186/s13059-018-1439-8) contains supplementary material, which is available to authorized users.
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影响因子：
29.4
作者：
Lambert JE;Ramos-Roman MA;Browning JD;Parks EJ
通讯作者：
Parks EJ
影响因子：
2.4
作者：
Felix, Deise Rosa;Costenaro, Fabiola;Coral, Gabriela Perdomo
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Coral, Gabriela Perdomo
影响因子：
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Lee, Joseph J.;Lambert, Jennifer E.;Parks, Elizabeth J.
通讯作者：
Parks, Elizabeth J.
影响因子：
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作者：
Kotronen, Anna;Seppanen-Laakso, Tuulikki;Oresic, Matej
通讯作者：
Oresic, Matej
影响因子：
12.3
作者：
Eiden M;Koulman A;Hatunic M;West JA;Murfitt S;Osei M;Adams C;Wang X;Chu Y;Marney L;Roberts LD;O'Rahilly S;Semple RK;Savage DB;Griffin JL
通讯作者：
Griffin JL