Hepatic and circulating levels of PCSK9 in morbidly obese patients: Relation with severity of liver steatosis |
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| Institution: | 1. Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;2. Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada;3. Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada;4. Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada;5. The Menopause Clinic, Shirley E. Greenberg Women''s Health Centre, The Ottawa Hospital, Department of Obstetrics and Gynecology, University of Ottawa, Canada;6. Division of Radiation Oncology, Ottawa Hospital Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada;7. Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Quebec, Canada;8. Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada;1. Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America;2. Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, United States of America |
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| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is becoming the main cause of liver disease in Western countries, especially in morbidly obese patients (MOPs). The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently studied because of its possible involvement in the pathogenesis of NAFLD, but its role, at least in MOPs, is still controversial. The aim of this study was to clarify the correlation between the circulating levels of the PCSK9 protein (cPCSK9) and its hepatic expression with the severity of liver damage in a population of MOPs with NAFLD undergoing bariatric surgery. PCSK9 mRNA was positively correlated with FASN, PPARγ and PPARα mRNAs, while no significant differences were found in PCSK9 mRNA expression in relation to the severity of liver steatosis, lobular inflammation and hepatocellular ballooning. In addition, hepatic PCSK9 protein expression levels were not related to histological parameters of lobular inflammation and hepatocyte ballooning, decreased significantly only in relation to the severity of hepatic steatosis, and were inversely correlated with ALT and AST serum levels. cPCSK9 levels in the whole population were associated with the severity of hepatic steatosis and were positively correlated to total cholesterol levels. In multivariate analysis, cPCSK9 levels were associated with age, total cholesterol and HbA1c. In conclusion, in MOPs our findings support a role for PCSK9 in liver fat accumulation, but not in liver damage progression, and confirm its role in the increase of blood cholesterol, which ultimately may contribute to increased cardiovascular risk in this population. |
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