Background & Aims: Fetuin-A is a liver-derived peptide associated with insulin resistance. Aim of this cross-sectional study was to evaluate whether Fetuin-A is increased in patients with nonalcoholic fatty liver disease (NAFLD) vs. healthy subjects without metabolic abnormalities and the association with insulin resistance and liver damage. To investigate the causal relationship between fatty liver and Fetuin-A, we also analysed whether the inherited I148M PNPLA3 variant modulates Fetuin-A. Methods: In 137 patients with histological NAFLD, complete metabolic characterization, PNPLA3 genotype, and in 260 healthy subjects without metabolic alterations, Fetuin-A was measured by enzyme-linked immunoabsorbent assay. Results: Serum Fetuin-A was higher in NAFLD patients than in controls (P < 0·0001), independently of age, sex, BMI, insulin resistance, dyslipidemia, adiponectin, PNPLA3 I148M and ALT levels (OR 1·006 95% CI 1·003-1·11; P = 0·003). In NAFLD patients, Fetuin-A was associated with steatosis severity (P = 0·03) and metabolic syndrome features, but not with hepatic inflammation. At multivariate analysis, Fetuin-A levels were associated with BMI, triglycerides, hyperglycemia and PNPLA3 I148M (P = 0·034) independently also of age, sex and ALT levels. As PNPLA3 I148M is a strong and inherited determinant of liver fat without affecting insulin resistance and lipid levels, these data suggest that steatosis has a causal role in determining serum Fetuin-A levels. Conclusions: Liver fat accumulation and the I148M variant of PNPLA3 are associated with serum Fetuin-A levels independently of insulin resistance. Fetuin-A may be implicated in the pathogenesis of metabolic complications associated with NAFLD.

Hepatic steatosis and PNPLA3 I148M variant are associated with serum Fetuin-A independently of insulin resistance / R. Rametta, M. Ruscica, P. Dongiovanni, C. Macchi, A.L. Fracanzani, L. Steffani, S. Fargion, P. Magni, L. Valenti. - In: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0014-2972. - 44:7(2014 Jul), pp. 627-633. [10.1111/eci.12280]

Hepatic steatosis and PNPLA3 I148M variant are associated with serum Fetuin-A independently of insulin resistance

R. Rametta;M. Ruscica;P. Dongiovanni;C. Macchi;A.L. Fracanzani;S. Fargion;P. Magni;L. Valenti
2014-07

Abstract

Background & Aims: Fetuin-A is a liver-derived peptide associated with insulin resistance. Aim of this cross-sectional study was to evaluate whether Fetuin-A is increased in patients with nonalcoholic fatty liver disease (NAFLD) vs. healthy subjects without metabolic abnormalities and the association with insulin resistance and liver damage. To investigate the causal relationship between fatty liver and Fetuin-A, we also analysed whether the inherited I148M PNPLA3 variant modulates Fetuin-A. Methods: In 137 patients with histological NAFLD, complete metabolic characterization, PNPLA3 genotype, and in 260 healthy subjects without metabolic alterations, Fetuin-A was measured by enzyme-linked immunoabsorbent assay. Results: Serum Fetuin-A was higher in NAFLD patients than in controls (P < 0·0001), independently of age, sex, BMI, insulin resistance, dyslipidemia, adiponectin, PNPLA3 I148M and ALT levels (OR 1·006 95% CI 1·003-1·11; P = 0·003). In NAFLD patients, Fetuin-A was associated with steatosis severity (P = 0·03) and metabolic syndrome features, but not with hepatic inflammation. At multivariate analysis, Fetuin-A levels were associated with BMI, triglycerides, hyperglycemia and PNPLA3 I148M (P = 0·034) independently also of age, sex and ALT levels. As PNPLA3 I148M is a strong and inherited determinant of liver fat without affecting insulin resistance and lipid levels, these data suggest that steatosis has a causal role in determining serum Fetuin-A levels. Conclusions: Liver fat accumulation and the I148M variant of PNPLA3 are associated with serum Fetuin-A levels independently of insulin resistance. Fetuin-A may be implicated in the pathogenesis of metabolic complications associated with NAFLD.
Fetuin-A; Insulin resistance; Nonalcoholic fatty liver disease; Pnpla3; Steatosis
Settore MED/09 - Medicina Interna
Settore MED/04 - Patologia Generale
Settore MED/05 - Patologia Clinica
Settore MED/13 - Endocrinologia
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Article (author)
File in questo prodotto:
File Dimensione Formato  
eci12280.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 160.37 kB
Formato Adobe PDF
160.37 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/240047
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 19
social impact