Pattern of Expression of Adiponectin Receptors in Human Liver and its Relation to Nonalcoholic Steatohepatitis
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Adiponectin has antisteatosis–anti-inflammatory properties and its circulating levels are reduced in nonalcoholic steatohepatitis (NASH).
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.
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.
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.
KeywordsAdiponectin Adiponectin receptors Obesity Nonalcoholic steatohepatitis
- AdipoR1 and AdipoR2
adiponectin receptor gene
nonalcoholic fatty liver disease
polymerase chain reaction
subcutaneous adipose tissue
visceral adipose tissue
This work was aided in part by a grant (PRIN prot. 2005067481) from the Italian Ministry of Research and Education.
We have not had, in the previous 12 months, a relevant duality of interest with a company whose products or services are directly related to the subject matter of our manuscript.
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