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Published on: July 19, 2024
Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies
John Willy Haukeland1, Tuva B Dahl, Arne Yndestad
1Department of Gastroenterology Research Institute for Internal Medicine, Oslo University Hospital Ullevål, PB 4950, 0424 Oslo, Norway. j.w.haukeland@medisin.uio.no
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 (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.
