The hepatic apelin system: A new therapeutic target for liver disease

Abstract

Apelin is a new member of adipose tissue–derived peptides which is also produced in the endothelial cells in various parts of the body.1 It is synthesized as a prepropeptide, and smaller peptides having higher potency are subsequently produced by posttranslational modification. It works through a cell surface G protein–coupled receptor called APJ, which has structural similarity with angiotensin type I receptor.2 In a recent issue of HEPATOLOGY, we read with great interest the article by Principe et al. investigating the apelin system in advanced liver disease.3 In conclusion, the authors pointed out the selective hepatic activation of the apelin system, together with the drop in fibrosis and neoangiogenesis and the improvement in cardiovascular and excretory function resulting from apelin receptor blockade. This work is important because it provides scientific information on this relevant issue. However, we have two major comments on this article. First, there is no data about the body mass index, blood pressure, insulin sensitivity, blood glucose, and lipid profiles of the subjects with cirrhosis. It is well known that plasma insulin and adipokine levels differ according to the degree of glucose dysregulation.4, 5 This point is also true for hypertension or elevated blood pressure.6 Plasma apelin levels were reported to increase in obesity in association with hyperinsulinemia.7 In addition, we recently showed decreased circulating apelin levels in subjects with dyslipidemia and also type 2 diabetes mellitus.8, 9 Secondly, no information about the drug use of the subjects could be seen in the text. We know that circulating adipokines and measures of insulin sensitivity are easily affected from the medications started for the metabolic problems mentioned above. Moreover, we just reported the changes of blood apelin concentrations after the statin treatment.10 We think all these points make the resultant comparisons and correlations questionable. Therefore, we would like to ask the authors whether they can present some new results by categorizing the patients according to metabolic confounders such as diabetes mellitus, hypertension, and dyslipidemia. This may provide the readers clearer information about the role of the apelin system in advanced liver diseases. Teoman Dogru*, Cemal Nuri Ercin*, Gokhan Erdem , Guldem Kilciler*, Serkan Tapan , * Department of Gastroenterology, Gulhane Medical School, Ankara, Turkey, Department of Internal Medicine, Gulhane Medical School, Ankara, Turkey, Department of Biochemistry, Gulhane Military Medical Academy, Ankara, Turkey.