Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis.
Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis.
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DOI：
10.1097/meg.0b013e328345c8c7
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发表时间：
2011-05
影响因子：
2.1
通讯作者：
Kalhan SC
中科院分区：
文献类型：
--
作者：
Dasarathy S;Yang Y;McCullough AJ;Marczewski S;Bennett C;Kalhan SC
对非酒精性脂肪性肝炎(NASH)患者的研究数据表明，肝脏脂肪酸氧化增加。我们先前已经显示NASH患者的空腹血浆胆汁酸浓度较高。体内和体外研究表明，胆汁酸通过与过氧化体增殖物激活受体α结合，激活成纤维细胞生长因子21(FGF21)，增加肝脏脂肪酸氧化。对健康对照组(n=38)和经活检证实的NASH患者(n=36)的血浆胆汁酸水平进行量化。测定了16例健康对照组和10例NASH患者空腹及脂内注射3h后的血浆脂肪酸、β-羟丁酸、胰岛素、血糖、瘦素、丙氨酸氨基转移酶、成纤维细胞生长因子21和氧化应激指标8-羟基脱氧鸟苷的浓度。在这些患者中的一个亚组(n=6)，对血浆神经酰胺亚型进行了量化。NASH患者空腹血浆胆汁酸、FGF21和瘦素浓度显著升高。脂肪注射后，对照组和NASH组血浆β-羟丁酸和游离脂肪酸水平均升高，但β-羟丁酸/游离脂肪酸比值高于NASH组(P=0.0 2)。仅NASH患者的血浆FGF21浓度因脂肪乳剂的作用而升高(P<；0.01)。脂内注射后，两组患者的血浆瘦素、胰岛素、血糖和丙氨酸转移酶浓度均无变化。脂肪内脂对总神经酰胺的增加在NASH组更大。胆汁酸和FGF21升高可能是NASH肝脏脂肪酸氧化升高的原因。
Data from studies in patients with nonalcoholic steatohepatitis (NASH) suggest an increased hepatic fatty acid oxidation. We have previously shown higher fasting plasma bile acid concentrations in patients with NASH. In-vivo and in-vitro studies suggest that bile acids by binding to peroxisome proliferator-activated receptor α activate fibroblast growth factor 21 (FGF21) and increase hepatic fatty acid oxidation. Plasma bile acid levels were quantified in healthy controls (n = 38) and patients with biopsy-proven NASH (n = 36). Plasma concentration of fatty acids, β-hydroxybutyrate, insulin, glucose, leptin, alanine aminotransferase, FGF21, and 8-hydroxydeoxyguanosine, a measure of oxidative stress, were measured in 16 healthy controls and 10 patients with NASH in the fasted state and in response to 3 h of infusion of intralipid. In a subgroup of these patients (n = 6 each), plasma ceramide subspecies were quantified. Fasting plasma bile acids, FGF21, and leptin concentrations were significantly higher in patients with NASH. In response to intralipid infusion there was an increase in plasma β-hydroxybutyrate and free fatty acid levels in both controls and NASH; however, the ratio of β-hydroxybutyrate/free fatty acid was higher in NASH (P = 0.02). Plasma FGF21 concentration increased in response to intralipid in patients with NASH only (P < 0.01). Plasma leptin, insulin, glucose, and alanine transferase concentrations did not change in either group after infusion of intralipid. Increase in total ceramides in response to intralipid was greater in NASH. Elevated bile acids and FGF21 may be responsible for the higher hepatic fatty acid oxidation in NASH.