Middle- and high-molecular weight adiponectin levels in relation to nonalcoholic fatty liver disease.

Kun Lian,Qin Wang,Hao‐Lin Liu,Cheng‐Xiang Li,Lei Zhou,Yu‐Nan Feng,Rong Li,Peng Han

doi:10.1002/jcla.23148

Abstract

ObjectiveAdiponectin (APN) circulates as high‐molecular weight (HMW), medium‐molecular weight (MMW), and low‐molecular weight (LMW) forms. Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Currently, the role of LMW, MMW, and HMW APN remains largely unclear in NAFLD.MethodsWe examined the variation of these forms and analyzed the related clinical characteristics in NAFLD. A total of 63 male NAFLD patients (mean age: 43.00 ± 6.10 years) and 70 healthy male subjects (mean age: 42.53 ± 7.98 years) were included in the study. Total APN and other clinical characteristics were measured. The changes in HMW, MMW, and LMW APN were determined in NAFLD patients and NAFLD patients on a high‐fat diet, and the association between the groups was further analyzed.ResultsDecreased levels of total APN and three APN isoforms were found in NAFLD. Significantly decreased levels of HMW (P < .01) and MMW (P < .001) were observed in NAFLD of high‐fat diet patients. In NAFLD patients, height (R = −.270, P = .032) and N‐epsilon‐(carboxymethyl) lysine (R = −.259, P = .040) significantly correlated with total APN. HMW APN was significantly associated with fasting plasma glucose (R = .350, P = .016), alanine aminotransferase (R = −.321, P = .029), and aspartate aminotransferase (R = −.295, P = .045). Additionally, MMW APN was significantly associated with total cholesterol (R = .357, P = .014) and high‐density lipoprotein (R = .556, P < .0001). Low‐density lipoprotein (R = −.283, P = .054) was also clearly associated with LMW APN in NAFLD patients.ConclusionThese results suggest that HMW and MMW APN may be involved in the pathogenesis and progression of NAFLD.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation of equal to and greater than 5% and is a common cause of chronic liver disease.[1,2] Nonalcoholic fatty liver disease spans a clinicopathologic spectrum characterized by hepatic steatosis with or without other pathologic features in the absence of other specific causes of fatty liver.[3,4] Based on the epidemiological data, the global prevalence of NAFLD has been estimated as high as one billion cases.[3]
We have reached the following findings: First, we found that the total APN and the distribution of APN isoforms were decreased in NAFLD patients
N-epsilon-(carboxymethyl) lysine (CML) was significantly negatively correlated with total APN in NAFLD patients, which is in alignment with a study conducted by Del Turco, et al[17] The corresponding soluble receptor for advanced glycation end product (sRAGE) levels indicated a significant decrease in NAFLD patients, which was in positive association with total APN

Summary

| INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation of equal to and greater than 5% and is a common cause of chronic liver disease.[1,2] Nonalcoholic fatty liver disease spans a clinicopathologic spectrum characterized by hepatic steatosis with or without other pathologic features in the absence of other specific causes of fatty liver.[3,4] Based on the epidemiological data, the global prevalence of NAFLD has been estimated as high as one billion cases.[3]. Adiponectin (APN) is a hormone produced by adipocytes that acts on specific receptors of several tissues through autocrine, paracrine, and endocrine signaling mechanisms. It exists as three distinct and basic oligomeric complexes in plasma as the homotrimer (low-molecular weight, LMW “mass,” ∼70 kDa) APN, the hexamer (middle-molecular weight, MMW “mass,” ∼140 kDa) APN, and 12-18 protomer (high-molecular weight, HMW “mass,” >300 kDa) APN.[7,8] Adiponectin plays an important pathophysiological role in metabolic activities such as glucose, lipid, and branched-chain amino acid metabolism and functions as an insulin sensitizer. The aim of the present study was to investigate the variance in levels of the three oligomers of APN and assess their relation to other parameters in Chinese NAFLD patients

| MATERIALS AND METHODS

Findings

| DISCUSSION