López-Bermejo Abel, Botas Patricia, Funahashi Tohru, Delgado Elías, Kihara Shinji, Ricart Wifredo, Fernández-Real José Manuel
Unit of Diabetes, Endocrinology and Nutrition, University Hospital of Girona Dr Josep Trueta, Girona, Spain.
Clin Endocrinol (Oxf). 2004 Feb;60(2):256-63. doi: 10.1046/j.1365-2265.2004.01977.x.
Insulin resistance plays a major aetiological role in the development of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin resistance and liver damage, we wished to study whether low circulating adiponectin would be associated with higher serum concentrations of liver enzymes in healthy subjects.
Cross-sectional, population-based study dealing with diabetes prevalence in northern Spain.
Two hundred and fifty-seven apparently healthy Caucasian subjects consecutively enrolled in the study.
Adiponectin serum levels were measured by enzyme-linked immunosorbent assay (ELISA), liver function tests (LFTs) by colourimetry and insulin resistance by the homeostasis model of assessment (HOMA value).
Adiponectin levels were negatively correlated with alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT), before and after adjustment for sex, age, body mass index (BMI) and insulin resistance (ALT; r = -0.32, P < 0.001; adjusted: r = -0.13, P = 0.033; GGT; r = -0.31, P < 0.001; adjusted: r = -0.16, P = 0.011). Additionally, adiponectin correlated with alkaline phosphate (ALKP) only after adjusting for the same confounding variables (r =-0.10, P = 0.098; adjusted: r = -0.14, P = 0.031). A general linear model, adjusting for age, sex and BMI, was constructed to predict the decrease in circulating adiponectin for each LFT value (i.e. ALT, GGT and ALKP) above the median. Beyond one LFT value above the median, serum adiponectin decreased by -0.97 mg/l (95% CI -1.46 to -0.48). In multiple regression analysis, sex, BMI and adiponectin, but not insulin resistance, predicted serum concentrations of both ALT and GGT, explaining 19% and 14% of their variance, respectively. Age, BMI and adiponectin, but not sex or insulin resistance, explained 20% of ALKP variance.
Adiponectin levels are associated in healthy humans with plasma concentrations of various liver function tests. The contributions of adiponectin to maintaining liver integrity through the regulation of both insulin sensitivity and/or the inflammatory response merit further studies.
胰岛素抵抗在脂肪肝疾病的发展中起主要病因作用。脂联素是一种肝脏胰岛素增敏剂，也是肿瘤坏死因子的抑制剂，肿瘤坏死因子是一种已知可诱导胰岛素抵抗和肝损伤的细胞因子，我们希望研究健康受试者中循环脂联素水平低是否与血清肝酶浓度升高有关。
基于人群的横断面研究，涉及西班牙北部的糖尿病患病率。
连续纳入该研究的257名表面健康的白种人受试者。
通过酶联免疫吸附测定（ELISA）测量脂联素血清水平，通过比色法测量肝功能测试（LFTs），并通过稳态模型评估（HOMA值）测量胰岛素抵抗。
在对性别、年龄、体重指数（BMI）和胰岛素抵抗进行校正之前和之后，脂联素水平与丙氨酸氨基转移酶（ALT）和γ-谷氨酰转肽酶（GGT）呈负相关（ALT；r = -0.32，P < 0.001；校正后：r = -0.13，P = 0.033；GGT；r = -0.31，P < 0.001；校正后：r = -0.16，P = 0.011）。此外，仅在对相同的混杂变量进行校正后，脂联素才与碱性磷酸酶（ALKP）相关（r = -0.10，P = 0.098；校正后：r = -0.14，P = 0.031）。构建了一个校正年龄、性别和BMI的一般线性模型，以预测每个高于中位数的LFT值（即ALT、GGT和ALKP）时循环脂联素水平的下降。在高于中位数的一个LFT值以上，血清脂联素下降了-0.97 mg/l（95%CI -1.46至-0.48）。在多元回归分析中，性别、BMI和脂联素而非胰岛素抵抗可预测ALT和GGT的血清浓度，分别解释其变异的19%和14%。年龄、BMI和脂联素而非性别或胰岛素抵抗解释了ALKP变异的20%。
在健康人群中，脂联素水平与各种肝功能测试的血浆浓度相关。脂联素通过调节胰岛素敏感性和/或炎症反应对维持肝脏完整性的作用值得进一步研究。
