Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies

Abstract

Objective: Fetuin A has been associated with insulin resistance and the metabolic syndrome. We therefore explored the role of fetuin A in nonalcoholic fatty liver disease (NAFLD). Design: Cross-sectional and intervention studies. Methods: We included 111 subjects with histologically proven NAFLD of whom 44 participated in a randomized, controlled trial with metformin. One hundred and thirty-one healthy subjects and 13 subjects undergoing hepatic surgery for metastatic cancer served as controls. Main outcome variables were circulating levels of fetuin A according to the presence of NAFLD, hepatic gene expression of fetuin A and key enzymes in glucose and lipid metabolism, and the effect of metformin on fetuin A levels in vivo and in vitro (HepG2 cells). Results: Fetuin A levels were significantly higher in NAFLD patients compared with controls (324G98 vs 225G75 mg/l, P!0.001). NAFLD was a significant predictor of elevated fetuin A levels (bZ174 (95% confidence interval: 110-234)) independent of body mass index, age, sex, fasting glucose, and triglycerides. Hepatic fetuin A mRNA levels correlated significantly with hepatic mRNA levels of key enzymes in lipid (sterol regulatory element-binding protein 1c, carnitine palmitoyltransferase 1) and glucose (phosphoenol pyruvate kinase 1, glucose-6-phosphatase) metabolism. Plasma fetuin A levels decreased significantly after metformin treatment compared with placebo (K40G47 vs 15G82 mg/l, PZ0.008). Metformin induced a dose-dependent decrease in fetuin A secretion in vitro. Conclusions: Fetuin A levels were elevated in NAFLD. Hepatic expression of fetuin A correlated with key enzymes in glucose and lipid metabolism. Metformin decreased fetuin A levels in vitro.

Serum Fetuin A Level, Liver Enzymes Activities and Insulin Resistance in Patients with Type 2 Diabetes

“…Fetuin-A has also been shown to correlate with liver fat in patients at risk of T2DM (Kantartzis et al, 2010). It has reported that there are a correlation between the fetuin-A gene expression and key enzymes in lipid and glucose metabolism (Haukeland et al, 2012). In our studies, γ-glutamyltransferase, ALT and AST levels were higher in type 2 diabetes when compared with control groups.…”

Effects of Turmeric on Homocysteine and Fetuin-A in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Double-Blind Placebo-Controlled Study

“…In some studies, hepatic fetuin-A expression and its serum levels increased in obesity and there was a strong association between the serum level of fetuin-A and liver fat accumulation (28,29). Hepatic expression of fetuin A is related to glucose and lipid metabolism (28).…”

“…In some studies, hepatic fetuin-A expression and its serum levels increased in obesity and there was a strong association between the serum level of fetuin-A and liver fat accumulation (28,29). Hepatic expression of fetuin A is related to glucose and lipid metabolism (28). Since fetuin-A is linked with fatty liver and insulin resistance, it may be considered as a new therapeutic target in NAFLD (28,29).…”

“…Hepatic expression of fetuin A is related to glucose and lipid metabolism (28). Since fetuin-A is linked with fatty liver and insulin resistance, it may be considered as a new therapeutic target in NAFLD (28,29).…”

The role of fetuin-A in cardiovascular diseases

“…A pioglitazonról, metforminról, statinokról és niacinról is közölték, hogy csökkentik a fetuin-A szintjét [16,21,48,49], és ugyanez a mérsékelt alkoholfogyasztásra is igaz [44]. Fetuin-A-szintet emelő hatása az ösztrogénterápiának van [44].…”