Betatrophin Levels Are Related to the Early Histological Findings in Nonalcoholic Fatty Liver Disease.

Alper Sonmez,Manfredi Rizzo,Ali Fuat Cicek,Teoman Dogru,Hasan Gurel,Cem Barcin,Cem Haymana,Cemal Nuri Ercin,Ali Kirik,Gurkan Celebi,Serkan Tapan,Halil Genc

doi:10.3390/metabo11070425

Abstract

Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32); non-NASH (n = 18)] and 30 healthy controls were included. Plasma betatrophin was measured by ELISA method. Insulin sensitivity was assessed by HOMA-IR index. Histological features were scored by the semi quantitative classification and combined as the NAFLD activity score (NAS). Betatrophin levels in the non-NASH group were significantly higher than the controls. Betatrophin was positively correlated to the age, waist circumference, total cholesterol, triglycerides, LDL cholesterol, glucose, insulin, HOMA-IR index and gamma glutamyl transpeptidase levels, and negatively correlated to the steatosis and NAS. In the stepwise linear regression analysis, the triglyceride (β = 0.457, p < 0.001), glucose (β = 0.281, p = 0.02) and NAS (β = −0.260, p = 0.03) were the independent determinants of betatrophin. Betatrophin levels are higher in the early stages of NAFLD and tend to decrease when the disease progresses. This could be an important preliminary mechanistic finding to explain the increased frequency of glucose intolerance during the course of NAFLD.

Highlights

The liver hormone betatrophin (ANGPTL8, Lipasin), which regulates glucose and lipid metabolism, has been identified by different groups, in different names [1,2,3,4]
The results of the present study show that the betatrophin levels significantly increase in the early stages of nonalcoholic fatty liver disease (NAFLD)
The results show that betatrophin levels are in close association with aging, visceral obesity, insulin resistance, glucose, trglycerides and gamma glutamyl transpeptidase (GGT)

Summary

Introduction

The liver hormone betatrophin (ANGPTL8, Lipasin), which regulates glucose and lipid metabolism, has been identified by different groups, in different names [1,2,3,4]. The preliminary report mentioning that betatrophin induces beta cell proliferation [1] was not replicated in the later studies [4,5]. It is still conceivable that Betatrophin may play a role in other ß-cell functions [6]. Searching for the role of betatrophin in the pathogenesis of chronic non-communicable diseases is very exciting as it may herald the emergence of promising new treatment modalities. The mechanism of the effect of betatrophin in physiological and pathological conditions is not clearly known. There is very few and controversial data about the role of betatrophin in chronic metabolic disorders such as obesity, metabolic syndrome and diabetes mellitus (DM). Some studies reported high betatrophin levels in both type

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