{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:48:10Z","timestamp":1763747290737,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Fetuin\u2010A is a liver\u2010derived peptide associated with insulin resistance. Aim of this cross\u2010sectional study was to evaluate whether Fetuin\u2010A is increased in patients with nonalcoholic fatty liver disease (<jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>) 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\u2010A, we also analysed whether the inherited I148M <jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3 variant modulates Fetuin\u2010A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 137 patients with histological <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>, complete metabolic characterization, <jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3 genotype, and in 260 healthy subjects without metabolic alterations, Fetuin\u2010A was measured by enzyme\u2010linked immunoabsorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum Fetuin\u2010A was higher in <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients than in controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001), independently of age, sex, <jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content>, insulin resistance, dyslipidemia, adiponectin, <jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3 I148M and <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> levels (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1\u00b7006 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1\u00b7003\u20131\u00b711; <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7003). In <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients, Fetuin\u2010A was associated with steatosis severity (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b703) and metabolic syndrome features, but not with hepatic inflammation. At multivariate analysis, Fetuin\u2010A levels were associated with <jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content>, triglycerides, hyperglycemia and <jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3 I148M (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7034) independently also of age, sex and <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> levels. As <jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3 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\u2010A levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Liver fat accumulation and the I148M variant of <jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3 are associated with serum Fetuin\u2010A levels independently of insulin resistance. Fetuin\u2010A may be implicated in the pathogenesis of metabolic complications associated with <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12280","type":"journal-article","created":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T15:44:47Z","timestamp":1400082287000},"page":"627-633","source":"Crossref","is-referenced-by-count":25,"title":["Hepatic steatosis and <scp>PNPLA<\/scp>3 I148<scp>M<\/scp> variant are associated with serum <scp>F<\/scp>etuin\u2010<scp>A<\/scp> independently of insulin resistance"],"prefix":"10.1111","volume":"44","author":[{"given":"Raffaela","family":"Rametta","sequence":"first","affiliation":[{"name":"Department of Pathophysiology and Transplantation Internal Medicine Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Ruscica","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Dongiovanni","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation Internal Medicine Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Macchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna L.","family":"Fracanzani","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation Internal Medicine Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Steffani","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Fargion","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation Internal Medicine Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Magni","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano Milano 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20030676"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.11.1445"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00737-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(00)00237-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"15489","DOI":"10.1016\/S0021-9258(18)55422-3","article-title":"Adipose conversion of 3T3\u2010L1 cells in a serum\u2010free culture system depends on epidermal growth factor, insulin\u2010like growth factor I, corticosteron, and cyclic AMP","volume":"265","author":"Schmidt W","year":"1990","journal-title":"J Biol 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