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首页> 外文期刊>Gastroenterology >JUKKA WESTERBACKA, ANNA KOTRONEN, BARBARA A. FIELDING, JOHN WAHREN, LEANNE HODSON, JULIA PERTTILA, TUULIKKI SEPPANEN-LAAKSO, TAPANI SUORTTI, JOHANNA AROLA, ROLF HULTCRANTZ, SANDRA CASTILLO, VESA M. OLKKONEN, KEITH N. FRAYN, MATEJ ORESIC, HANNELE YKI-JARVINEN
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JUKKA WESTERBACKA, ANNA KOTRONEN, BARBARA A. FIELDING, JOHN WAHREN, LEANNE HODSON, JULIA PERTTILA, TUULIKKI SEPPANEN-LAAKSO, TAPANI SUORTTI, JOHANNA AROLA, ROLF HULTCRANTZ, SANDRA CASTILLO, VESA M. OLKKONEN, KEITH N. FRAYN, MATEJ ORESIC, HANNELE YKI-JARVINEN

机译：尤卡·韦斯特巴克，安娜·科特隆宁，芭芭拉·A·菲尔丁，约翰·华伦，莱恩·霍德森，朱莉娅·佩蒂蒂拉，图利基·塞潘潘·拉科索，塔帕尼·索尔蒂，约翰内·阿罗拉，罗尔夫·赫尔克拉茨，桑德拉·卡斯蒂隆，韦萨，VESA，维萨汉妮·伊基·贾维宁

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BACKGROUND & AIMS: Animal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD. METHODS: We performed hepatic venous catheterization studies in combination with [~2H_2]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatog-raphy coupled to mass spectrometry. RESULTS: Concentrations of the endocannabinoid 2-arachidonoylg-lycerol were higher in arterialized (91 ± 33 mug/L basally) than in hepatic venous (51 ± 19 mug/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglyc-erides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states. CONCLUSIONS: The human fatty liver takes up 2-arachido-noylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.
机译：背景与目的：动物研究表明，内源性大麻素可能有助于非酒精性脂肪性肝病（NAFLD）的发展。此外，已显示NAFLD与肝活检中脂质浓度的多种变化有关。没有关于NAFLD受试者体内的内脏游离脂肪酸（FFA），甘油，酮体，内源性大麻素和脂质通量的数据。方法：我们对9例不同程度的肝脂肪变性患者进行了空腹静脉输注研究，并在空腹状态下[〜2H_2]棕榈酸酯输注和低剂量胰岛素输注期间进行了肝穿刺活检。使用超高效液相色谱-质谱联用技术测定内源性大麻素和单个脂质的内脏平衡。结果：动脉化血浆中内源性大麻素2-花生四烯酸-甘油的浓度（基础值为91±33杯/升）高于肝静脉血浆（51±19杯/升; P <.05）。空腹动脉（r = 0.72; P = .031）和肝静脉（r = 0.70; P = .037）浓度的2-花生四烯酰甘油与肝脂肪含量呈正相关。对85种不同的甘油三酸酯通量的分析表明，脂肪肝会过量产生饱和甘油三酸酯。在基础状态的血浆FFA组分中，肝动脉中棕榈油酸酯和亚油酸酯的相对量较低，而硬脂酸酯和油酸酯的相对量较高。在基础状态和胰岛素刺激状态下，动脉血静脉血浆和肝静脉中所有非甘油三酸酯脂质的绝对浓度均相当。结论：人的脂肪肝吸收了2-花生四烯酸-壬基甘油并过量生产了含有饱和脂肪酸的三酰基甘油，这可能反映了从头脂肪形成的增加。

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