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

• Published in: European journal of endocrinology Vol. 166; no. 3; pp. 503 - 510
• Main Authors: Haukeland, John Willy, Dahl, Tuva B, Yndestad, Arne, Gladhaug, Ivar P, Løberg, Else Marit, Haaland, Terese, Konopski, Zbigniew, Wium, Cecilie, Aasheim, Erlend T, Johansen, Odd Erik, Aukrust, Pål, Halvorsen, Bente, Birkeland, Kåre I
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.03.2012
• Subjects: Adult; alpha-2-HS-Glycoprotein - biosynthesis; alpha-2-HS-Glycoprotein - metabolism; Biological and medical sciences; Biomarkers - blood; Clinical Study; Cross-Sectional Studies; Dose-Response Relationship, Drug; Double-Blind Method; Endocrinopathies; Fatty Liver - drug therapy; Fatty Liver - metabolism; Fatty Liver - surgery; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Hep G2 Cells; Humans; Lipid Metabolism - physiology; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Metformin - pharmacology; Metformin - therapeutic use; Middle Aged; Non-alcoholic Fatty Liver Disease; Other diseases. Semiology; Vertebrates: endocrinology; In vivo; Non alcoholic steatohepatitis; Digestive diseases; Hepatic disease; Fetuin; In vitro; Endocrinology
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-11-0864

ObjectiveFetuin 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).DesignCross-sectional and intervention studies.MethodsWe 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).ResultsFetuin A levels were significantly higher in NAFLD patients compared with controls (324±98 vs 225±75 mg/l, P<0.001). NAFLD was a significant predictor of elevated fetuin A levels (β=174 (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 (−40±47 vs 15±82 mg/l, P=0.008). Metformin induced a dose-dependent decrease in fetuin A secretion in vitro.ConclusionsFetuin 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.