Adiponectin, hepatocellular dysfunction and insulin sensitivity.
OBJECTIVE
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.


METHODS
Cross-sectional, population-based study dealing with diabetes prevalence in northern Spain.


METHODS
Two hundred and fifty-seven apparently healthy Caucasian subjects consecutively enrolled in the study.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
López-Bermejo
Abel
A
Unit of Diabetes, Endocrinology and Nutrition, University Hospital of Girona Dr Josep Trueta, Girona, Spain. uden.alopez@htrueta.scs.es
Botas
Patricia
P
Funahashi
Tohru
T
Delgado
Elías
E
Kihara
Shinji
S
Ricart
Wifredo
W
Fernández-Real
José Manuel
JM
D052242:Adiponectin; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D016014:Linear Models; D008099:Liver / Q000201:enzymology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis*; D012737:Sex Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase