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Abstract
Background Adiponectin has antisteatosis–anti-inflammatory
properties and its circulating levels are reduced in nonalcoholic
steatohepatitis (NASH).
Methods To assess the role of adiponectin in NASH, we
measured expression of adiponectin gene ( APM1) and
receptors ( AdipoR1/AdipoR2) in liver and subcutaneous
and visceral fat in subjects with biopsy-proven NASH or
pure steatosis (PS). In 103 subjects undergoing gastric
bypass or elective abdominal surgery (17 with normal liver
histology (C), 52 with PS, and 34 with NASH), RNA was
extracted from tissue samples, and quantification of APM1,
AdipoR1 , and AdipoR2 was carried out by real-time
polymerase chain reaction.
Results In NASH vs C, circulating adiponectin levels (3.6
[2.4] vs 5.3[4.3] μg/ml, median[interquartile range], p<
0.05) and adiponectin concentrations, APM1, AdipoR1,
and AdipoR2 expression in visceral fat were all reduced
( p≤0.03). These differences disappeared when adjusting
for obesity. In contrast, liver AdipoR1 (1.40 [0.46] vs 1.00
[0.32] of controls) and AdipoR2 expression (1.20 [0.41] vs
0.78 [0.43]) were increased in NASH, and group differences
were statistically significant ( p<0.0001 for AdipoR1
and p=0.0001 for AdipoR2). Results for PS were generally
intermediate between NASH and C. Liver receptor
expression was reciprocally related to circulating adiponectin
( rho=−0.42, p<0.003 for AdipoR1 and rho=−0.26,
p <0.009 for AdipoR2). In multivariate models adjusting
for sex, age, fasting plasma glucose, and obesity, liver
enzymes levels were directly related to both AdipoR1 and
AdipoR2 expression in liver.
Conclusion In obese patients with NASH, adiponectin
receptors are underexpressed in visceral fat —as a likely
correlate of obesity —but overexpressed in liver, possibly as
a compensatory response to hypoadiponectinemia, and
positively associated with liver damage.
Keywords Adiponectin . Adiponectin receptors . Obesity.
Nonalcoholic steatohepatitis
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