In:
European Journal of Endocrinology, Oxford University Press (OUP), Vol. 166, No. 3 ( 2012-03), p. 503-510
Abstract:
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 (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 . 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 .
Type of Medium:
Online Resource
ISSN:
0804-4643
,
1479-683X
Language:
Unknown
Publisher:
Oxford University Press (OUP)
Publication Date:
2012
detail.hit.zdb_id:
1485160-X
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