Reeves Valerie L, Trybula Joy S, Wills Rachel C, Goodpaster Bret H, Dubé John J, Kienesberger Petra C, Kershaw Erin E
Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida, USA.
Obesity (Silver Spring). 2015 Dec;23(12):2371-6. doi: 10.1002/oby.21232. Epub 2015 Nov 2.
Autotaxin (ATX) is an adipocyte-derived lysophospholipase D that generates the lipid signaling molecule lysophosphatidic acid (LPA). The ATX/LPA pathway in adipose tissue has recently been implicated in obesity and insulin resistance in animal models, but the role of circulating ATX in humans remains unclear. The aim of the present study was to determine the relationship between serum ATX and insulin resistance.
Older (60-75 years), nondiabetic human participants with overweight or obesity (BMI 25-37 kg m(-2) ) were characterized for metabolic phenotype including measures of energy, glucose, and lipid homeostasis. The relationship between serum ATX and metabolic parameters was then determined using correlative and predictive statistics.
Serum ATX was higher in females than in males. After controlling for sex, serum ATX correlated with multiple measures of adiposity and glucose homeostasis/insulin action. Serum ATX and BMI also independently predicted glucose infusion rate during a hyperinsulinemic euglycemic clamp and homeostatic model assessment of insulin resistance after controlling for sex and medication use.
Serum ATX correlates with and predicts measures of glucose homeostasis and insulin sensitivity in older humans, suggesting that it may be a potential pathogenic factor and/or diagnostic/therapeutic target for insulin resistance in this population.
自分泌运动因子（ATX）是一种由脂肪细胞产生的溶血磷脂酶D，可生成脂质信号分子溶血磷脂酸（LPA）。脂肪组织中的ATX/LPA信号通路最近在动物模型中被认为与肥胖和胰岛素抵抗有关，但循环ATX在人类中的作用仍不清楚。本研究的目的是确定血清ATX与胰岛素抵抗之间的关系。
纳入年龄较大（60 - 75岁）、超重或肥胖（BMI 25 - 37 kg·m⁻²）的非糖尿病人类参与者，对其代谢表型进行特征分析，包括能量、葡萄糖和脂质稳态的测量。然后使用相关和预测统计方法确定血清ATX与代谢参数之间的关系。
女性血清ATX水平高于男性。在控制性别因素后，血清ATX与多种肥胖指标以及葡萄糖稳态/胰岛素作用指标相关。在控制性别和药物使用情况后，血清ATX和BMI还能独立预测高胰岛素正常血糖钳夹期间的葡萄糖输注率以及胰岛素抵抗的稳态模型评估值。
血清ATX与老年人的葡萄糖稳态和胰岛素敏感性指标相关且具有预测作用，提示它可能是该人群胰岛素抵抗的潜在致病因素和/或诊断/治疗靶点。
