Pramfalk Camilla, Pavlides Michael, Banerjee Rajarshi, McNeil Catriona A, Neubauer Stefan, Karpe Fredrik, Hodson Leanne
Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.P., C.A.M., F.K., L.H.), Oxford Centre for Clinical Magnetic Resonance Research (M.P., R.B., S.N.), University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom; and Translational Gastroenterology Unit (M.P.), John Radcliffe Hospital and National Institute for Health Research Oxford Biomedical Research Centre (F.K.), Oxford University Hospital Trusts, Oxford OX3 9DU, United Kingdom.
J Clin Endocrinol Metab. 2015 Dec;100(12):4425-33. doi: 10.1210/jc.2015-2649. Epub 2015 Sep 28.
In most populations a greater proportion of men have hepatic steatosis than women. Sex-specific differences in hepatic dietary fatty acid (FA) metabolism have not been well characterized. We compared fasting and postprandial hepatic FA synthesis (de novo lipogenesis [DNL]) and oxidation in men and women.
Fasting and postprandial hepatic FA metabolism was studied in 22 healthy men (n = 11) and women with similar age, body mass index, and liver fat content using metabolic substrates labeled with stable-isotope tracers ((2)H2O and [U(13)C]palmitate). Dietary FA oxidation was assessed by appearance of (13)C into plasma 3-hydroxybutyrate and breath CO2 as markers of liver and whole-body FA oxidation, respectively.
Despite similar liver fat content, fasting and postprandial plasma triacylglycerol (TG) concentrations were significantly (P < .05) higher in men compared with women. The appearance of (13)C from dietary FA into plasma 3-hydroxybutyrate and breath CO2 was greater (P < .05) in women compared with men. Although the contribution of DNL into very low-density lipoprotein (VLDL)-TG was similar (∼ 10%) in the fasting state, there was a divergence in pattern over the course of the study, with men maintaining a higher contribution of DNL to VLDL-TG than women (P = .006 time x sex interaction).
The combination of lower dietary FA oxidation and a prolonged increase in DNL observed in men may represent partitioning of FA into esterification and storage pathways within the liver, leading to greater VLDL-TG production, and predispose to the sex difference in hepatic steatosis.
在大多数人群中，患肝脂肪变性的男性比例高于女性。肝脏膳食脂肪酸（FA）代谢的性别差异尚未得到充分表征。我们比较了男性和女性空腹及餐后肝脏FA合成（从头脂肪生成[DNL]）与氧化情况。
使用稳定同位素示踪剂（（2）H2O和[U（13）C]棕榈酸）标记的代谢底物，对22名年龄、体重指数和肝脏脂肪含量相似的健康男性（n = 11）和女性进行空腹及餐后肝脏FA代谢研究。通过（13）C在血浆3 - 羟基丁酸中的出现情况以及呼出的CO2分别作为肝脏和全身FA氧化的标志物来评估膳食FA氧化。
尽管肝脏脂肪含量相似，但男性空腹和餐后血浆三酰甘油（TG）浓度显著（P <.05）高于女性。与男性相比，女性膳食FA中的（13）C在血浆3 - 羟基丁酸和呼出CO2中的出现量更大（P <.05）。尽管在空腹状态下DNL对极低密度脂蛋白（VLDL）-TG的贡献相似（约10%），但在研究过程中模式出现了差异，男性DNL对VLDL - TG的贡献高于女性（P =.006时间×性别交互作用）。
男性中观察到的较低膳食FA氧化和DNL持续增加的组合可能代表FA在肝脏内分配到酯化和储存途径，导致VLDL - TG产生增加，并易引发肝脂肪变性的性别差异。
