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Obesity Surgery

, Volume 19, Issue 4, pp 467–474 | Cite as

Pattern of Expression of Adiponectin Receptors in Human Liver and its Relation to Nonalcoholic Steatohepatitis

  • M. NannipieriEmail author
  • F. Cecchetti
  • M. Anselmino
  • E. Mancini
  • G. Marchetti
  • A. Bonotti
  • S. Baldi
  • B. Solito
  • M. Giannetti
  • A. Pinchera
  • F. Santini
  • E. Ferrannini
Research Article

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 

Abbreviations

APM1

adiponectin gene

ApN

adiponectin protein

AdipoR1 and AdipoR2

adiponectin receptor gene

GADPH

glyceraldehyde-3-phosphate dehydrogenase

HPRT

hypoxantine-phosphorybosyl-transferase

Ob

obesity

NAFLD

nonalcoholic fatty liver disease

NASH

nonalcoholic steatohepatitis

PS

pure steatosis

PCR

polymerase chain reaction

SAT

subcutaneous adipose tissue

VAT

visceral adipose tissue

Notes

Acknowledgement

This work was aided in part by a grant (PRIN prot. 2005067481) from the Italian Ministry of Research and Education.

Disclosure

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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Copyright information

© Italian Government 2008

Authors and Affiliations

  • M. Nannipieri
    • 1
    • 2
  • F. Cecchetti
    • 1
    • 2
  • M. Anselmino
    • 3
  • E. Mancini
    • 1
    • 2
  • G. Marchetti
    • 4
  • A. Bonotti
    • 1
    • 2
  • S. Baldi
    • 1
  • B. Solito
    • 3
  • M. Giannetti
    • 5
  • A. Pinchera
    • 5
  • F. Santini
    • 5
  • E. Ferrannini
    • 1
    • 2
  1. 1.Department of Internal MedicineUniversity of PisaPisaItaly
  2. 2.C.N.R Institute of Clinical PhysiologyUniversity of PisaPisaItaly
  3. 3.Unit of Bariatric SurgeryS. Chiara HospitalPisaItaly
  4. 4.Unit of PathologyS. Chiara HospitalPisaItaly
  5. 5.Department of EndocrinologyUniversity of PisaPisaItaly

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