Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease
Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease
复制标题
DOI：
10.1002/hep.25539
复制
发表时间：
2012-05-01
期刊：
影响因子：
13.5
通讯作者：
Cusi, Kenneth
中科院分区：
文献类型：
--
作者：
Lomonaco, Romina;Ortiz-Lopez, Carolina;Cusi, Kenneth
脂肪组织胰岛素抵抗在非酒精性脂肪性肝病（NAFLD）发病机制中的作用尚不清楚。为了评估这一点，我们测量了207名NAFLD患者（年龄= 51 +/- 1，体重指数= 34.1 +/- 0.3 kg/m2）和22名没有NAFLD的对照组（没有NAFLD）的脂肪组织胰岛素抵抗，方法是通过验证指数（Adipo-IRi =血浆游离脂肪酸[FFA] x胰岛素[FPI]浓度），以及在口服糖耐量试验和低剂量胰岛素输注期间血浆游离脂肪酸的抑制。我们还根据脂肪组织胰岛素抵抗的四分位数（Adipo-IRi四分位数：Q1 =更敏感；Q4 =更胰岛素抵抗）对脂肪组织胰岛素抵抗与代谢和组织学参数之间的关系进行了探讨。在3-[3H]葡萄糖的正糖胰岛素钳夹期间评估肝脏胰岛素抵抗，以内源性葡萄糖生成× FPI （HIRi）指数测量，以及肌肉胰岛素敏感性。通过磁共振成像和光谱学测量肝脏脂肪，并进行肝活检以评估肝脏组织学。与非脂肪变性患者相比，NAFLD患者在脂肪组织、肝脏和骨骼肌水平均出现胰岛素抵抗，血浆天冬氨酸转氨酶、丙氨酸转氨酶、甘油三酯水平升高，高密度脂蛋白胆固醇和脂联素水平降低（均P < 0.01）。代谢参数、肝脏胰岛素抵抗和肝纤维化（但不包括坏死炎症）随着脂肪组织胰岛素抵抗的加重而恶化（均P < 0.01）。结论：脂肪组织胰岛素抵抗在肥胖NAFLD患者代谢和组织学异常的发展中起关键作用。针对脂肪组织胰岛素抵抗的治疗策略（例如，减肥和噻唑烷二酮类药物）可能对这一人群有价值。(肝脏病学2012)
The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 +/- 1, body mass index = 34.1 +/- 0.3 kg/m2) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo-IRi = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low-dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo-IRi quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured as an index derived from endogenous glucose production x FPI (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3-[3H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high-density lipoprotein cholesterol and adiponectin levels (all P < 0.01). Metabolic parameters, hepatic insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all P < 0.01). Conclusion: Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population. (HEPATOLOGY 2012)