Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Diabetes Care. 2010 May;33(5):1134-9. doi: 10.2337/dc09-1765. Epub 2010 Feb 25.
Nonalcoholic fatty liver disease is highly prevalent in obese and type 2 diabetic individuals and is strongly associated with dyslipidemia and inflammation. Weight loss and/or pharmacotherapy are commonly used to correct these abnormalities.
We performed a 16-week intervention trial of a hypocaloric, low-fat diet plus 10 mg/day ezetimibe (n = 15) versus a hypocaloric, low-fat diet alone (n = 10) on intrahepatic triglyceride (IHTG) content, plasma high sensitivity-C-reactive protein (hs-CRP), adipocytokines, and fetuin-A concentrations and apolipoprotein (apo)B-100 kinetics in obese subjects. ApoB-100 metabolism was assessed using stable isotope tracer kinetics and compartmental modeling; liver and abdominal fat contents were determined by magnetic resonance techniques.
Both weight loss and ezetimibe plus weight loss significantly (all P < 0.05) reduced body weight, visceral and subcutaneous adipose tissues, insulin resistance and plasma triglycerides, VLDL-apoB-100, apoC-III, fetuin-A, and retinol-binding protein-4 and increased plasma adiponectin concentrations. Compared with weight loss alone, ezetimibe plus weight loss significantly (all P < 0.05) decreased IHTG content (-18%), plasma hs-CRP (-53%), interleukin-6 (-24%), LDL cholesterol (-18%), campesterol (-59%), and apoB-100 (-14%) levels, with a significant increase in plasma lathosterol concentrations (+43%). The LDL-apoB-100 concentration also significantly fell with ezetimibe plus weight loss (-12%), chiefly owing to an increase in the corresponding fractional catabolic rate (+29%). The VLDL-apoB-100 secretion rate fell with both interventions, with no significant independent effect of ezetimibe.
Addition of ezetimibe to a moderate weight loss diet in obese subjects can significantly improve hepatic steatosis, inflammation, and LDL-apoB-100 metabolism.
非酒精性脂肪性肝病在肥胖和 2 型糖尿病患者中非常普遍，并且与血脂异常和炎症密切相关。通常采用减轻体重和/或药物治疗来纠正这些异常。
我们进行了一项为期 16 周的干预试验，比较了低热量、低脂饮食加 10 毫克/天依泽替米贝（n = 15）与单独低热量、低脂饮食（n = 10）对肥胖患者肝内甘油三酯（IHTG）含量、血浆高敏 C 反应蛋白（hs-CRP）、脂肪细胞因子和胎球蛋白-A 浓度以及载脂蛋白（apo）B-100 动力学的影响。使用稳定同位素示踪动力学和房室模型评估 apoB-100 代谢；通过磁共振技术测定肝和腹部脂肪含量。
体重减轻和依泽替米贝加体重减轻均显著（均 P < 0.05）降低体重、内脏和皮下脂肪组织、胰岛素抵抗和血浆甘油三酯、VLDL-apoB-100、apoC-III、胎球蛋白-A 和视黄醇结合蛋白-4，并增加血浆脂联素浓度。与单独减轻体重相比，依泽替米贝加体重减轻显著（均 P < 0.05）降低 IHTG 含量（-18%）、血浆 hs-CRP（-53%）、白细胞介素-6（-24%）、LDL 胆固醇（-18%）、菜油固醇（-59%）和 apoB-100（-14%）水平，并显著增加血浆羊毛甾醇浓度（+43%）。LDL-apoB-100 浓度也随依泽替米贝加体重减轻显著下降（-12%），主要归因于相应的分解代谢率增加（+29%）。两种干预措施均降低了 VLDL-apoB-100 分泌率，但依泽替米贝无独立作用。
在肥胖患者中，将依泽替米贝添加到适度减轻体重的饮食中可显著改善肝脏脂肪变性、炎症和 LDL-apoB-100 代谢。
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