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ORIGINAL RESEARCH ARTICLE

Leptin Receptor Isoforms mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Viral Hepatitis

Nikolaos Stefanou^*, Maria Satra^*, Vassilios Papanikolaou^*, Fani Kalala, Nikolaos Gatselis, Anastasios Germenis, George N. Dalekos and Aspasia Tsezou^*,,1

^* University of Thessaly, Medical School, Department of Biology, 41222 Larissa, Greece; University of Thessaly, Medical School, Department of Immunology, 41222 Larissa, Greece; University of Thessaly, Medical School, Department of Medicine, Academic Liver Unit, 41222 Larissa, Greece; and University of Thessaly, Medical School, Laboratory of Cytogenetics and Medical Genetics, 41222 Larissa, Greece

To whom requests for reprints should be addressed at ¹ University of Thessaly, Faculty of Health Sciences, Medical School, Department of Biology, 22 Papakyriazi Street, 41222 Larissa, Greece. E-mail: atsezou{at}med.uth.gr

There is accumulating evidence that leptin has a pleiotropic role in hematopoiesis, immune response, fibrogenesis, and hepatocarcinogenesis. We investigated the expression of leptin and leptin receptor (OB-R) at the protein level by flow cytometry and also quantified by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) the two major leptin receptor isoforms (OB-Rl, OB-Rs) in peripheral blood mononuclear cells (PBMCs) of patients with hepatitis B (HBV; n = 31), hepatitis C (HCV; n = 34), and nonviral liver disease (n = 25), and healthy controls (n = 36), as well as in liver tissues of HBV (n = 8), HCV (n = 7), and healthy individuals (n = 6). Serum leptin levels were measured in all participants (N = 126). We observed significantly lower OB-Rl and OB-Rs mRNA levels in PBMCs of HBV and HCV patients compared with healthy controls and nonviral liver disease patients (P < 0.05). Flow cytometry analysis confirmed the real-time RT-PCR results. Expression of leptin and OB-Rl was significantly increased in viral hepatitis liver tissues compared with healthy tissues (P < 0.01). OB-Rl mRNA levels were not associated with hepatitis patients’ clinical status (inactive, chronic hepatitis, or cirrhosis). We also found decreased serum leptin in HBV and HCV patients compared with healthy individuals and the nonviral liver disease group. Leptin was expressed in 3 of 34 HCV (8.8%) and 19 of 25 (76%) nonviral liver disease patients. Moreover, expression of OB-Rl and OB-Rs were associated when all individuals were grouped together (r = 0.78, P < 0.001). In conclusion, our findings may suggest the involvement of the leptin system in the immunopathology of chronic viral hepatitis.

Key Words: leptin • leptin receptors • hepatitis B virus • hepatitis C virus • cirrhosis