Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA.
Eur J Gastroenterol Hepatol. 2011 May;23(5):382-8. doi: 10.1097/MEG.0b013e328345c8c7.
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.
来自非酒精性脂肪性肝炎（NASH）患者研究的数据表明肝脂肪酸氧化增加。我们之前已经表明 NASH 患者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物酶体增殖物激活受体-α结合激活成纤维细胞生长因子 21（FGF21）并增加肝脂肪酸氧化。
在健康对照组（n=38）和经活检证实的 NASH 患者（n=36）中定量测定血浆胆汁酸水平。在空腹状态下和在输注中 3 小时内，在 16 名健康对照者和 10 名 NASH 患者中测量了血浆脂肪酸、β-羟丁酸、胰岛素、葡萄糖、瘦素、丙氨酸氨基转移酶、FGF21 和 8-羟基脱氧鸟苷的浓度，8-羟基脱氧鸟苷是氧化应激的衡量标准。在这些患者的亚组中（n=6 人），定量测定了血浆神经酰胺亚种。
NASH 患者的空腹血浆胆汁酸、FGF21 和瘦素浓度明显更高。在输注中，对照组和 NASH 患者的血浆β-羟丁酸和游离脂肪酸水平均升高；然而，NASH 中的β-羟丁酸/游离脂肪酸比值更高（P=0.02）。仅在 NASH 患者中，FGF21 对输注中脂肪乳的反应增加（P<0.01）。在输注脂肪乳后，两组的血浆瘦素、胰岛素、葡萄糖和丙氨酸转氨酶浓度均未发生变化。对脂肪乳的总神经酰胺反应增加在 NASH 中更大。
升高的胆汁酸和 FGF21 可能是 NASH 中肝脂肪酸氧化增加的原因。
