Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease.
Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease.
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DOI：
10.1053/j.gastro.2013.11.049
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发表时间：
2014-03
期刊：
影响因子：
29.4
通讯作者：
Parks EJ
中科院分区：
文献类型：
--
作者：
Lambert JE;Ramos-Roman MA;Browning JD;Parks EJ
关于新生脂肪生成在非酒精性脂肪性肝病（NAFLD）发展中的作用的研究很少。我们使用同位素分析来比较患有NAFLD的个体和没有代谢因素匹配的个体（对照）之间的从头脂肪生成和脂肪酸通量。我们研究了患有代谢综合征和/或丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平>30 mU/L的受试者，使用磁共振波谱来识别肝内三酰甘油水平高（HighLF，n=13）或低水平（LowLF，n=11）的受试者。收集所有参与者的临床和人口统计学信息，并使用胰岛素改良的静脉葡萄糖耐量试验测量胰岛素敏感性。给予稳定同位素，并使用气相色谱-质谱法分析游离（非酯化）脂肪酸（FFA）和三酰甘油通量和脂肪生成。高LF个体（18.4%±3.6%）夜间血浆FFA水平和胰岛素浓度高于低LF个体（3.1%±2.7%;分别为P= 0.04和P<0.001）。两组间FFA的脂肪流量（高LF组为414±195 μmol/min，低LF组为358±105 μmol/min; P= 0.41）或FFA产生极低密度脂蛋白三酰甘油（4.06±2.57 μmol/min，低LF组为4.34±1.82 μmol/min; P= 0.77）无差异。相比之下，高LF受试者的从头脂肪酸合成率比低LF受试者高3倍以上（2.57±1.53 μmol/min vs 0.78±0.42 μmol/min; P= 0.001）。作为棕榈酸三酰甘油的百分比，HighLF受试者的新生脂肪生成高2倍（23.2%±7.9% vs 10.1% ±6.7%; P<0.001）;该水平与肝内三酰甘油水平独立相关（r=0.53; P= 0.007）。通过对NAFLD患者和对照组给予同位素，我们证实了NAFLD患者增加了脂肪酸的合成。NAFLD受试者的夜间血浆FFA水平也较高，并且在禁食后不能抑制新生脂肪生成的作用。这些发现表明脂肪生成可能是NAFLD的治疗靶点。
There have been few studies on the role of de novo lipogenesis in the development of nonalcoholic fatty liver disease (NAFLD). We used isotope analyses to compare de novo lipogenesis and fatty acid flux between individuals with NAFLD and those without, matched for metabolic factors (controls). We studied subjects with metabolic syndrome and/or levels of alanine aminotransferase and aspartate aminotransferase >30 mU/L, using magnetic resonance spectroscopy to identify those with high levels (HighLF, n=13) or low levels of intrahepatic triacylglycerol (LowLF, n=11). Clinical and demographic information was collected from all participants, and insulin sensitivity was measured using the insulin-modified intravenous glucose tolerance test. Stable isotopes were administered and gas chromatography with mass spectrometry was used to analyze free (non-esterified) fatty acid (FFA) and triacylglycerol flux and lipogenesis. Individuals with HighLF (18.4%±3.6%) had higher plasma levels of FFA during the nighttime and concentrations of insulin than subjects with LowLF (3.1%±2.7%; P=.04 and P<.001, respectively). No differences were observed between groups in adipose flux of FFA (414±195 μmol/min for HighLF vs 358±105 μmol/min for LowLF; P=.41) or production of very low-density lipoprotein triacylglycerols from FFA (4.06±2.57 μmol/min vs 4.34±1.82 μmol/min; P=.77). By contrast, subjects with HighLF had more than 3-fold higher rates of de novo fatty acid synthesis than subjects with LowLF (2.57±1.53 μmol/min vs 0.78±0.42 μmol/min; P=.001). As a percentage of triacylglycerol palmitate, de novo lipogenesis was 2-fold higher in subjects with HighLF (23.2%±7.9% vs 10.1 %±6.7%; P<.001); this level was independently associated with the level of intrahepatic triacylglycerol (r=0.53; P=.007). By administering isotopes to individuals with NAFLD and control subjects, we confirmed that those with NAFLD increase synthesis of fatty acids. Subjects with NAFLD also had higher nocturnal plasma levels of FFA and did not suppress the contribution from de novo lipogenesis upon fasting. These findings indicate that lipogenesis might be a therapeutic target for NAFLD.
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DOI：
10.1073/pnas.0914798107
发表时间：
2010-02-23
影响因子：
11.1
作者：
Li, Shijie;Brown, Michael S.;Goldstein, Joseph L.
通讯作者：
Goldstein, Joseph L.
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
影响因子：
15.9
作者：
Chen, XH;Iqbal, N;Boden, G
通讯作者：
Boden, G
影响因子：
13.5
作者：
Haufe, Sven;Engeli, Stefan;Jordan, Jens
通讯作者：
Jordan, Jens