title: Decreased plasma endogenous soluble RAGE, and enhanced adipokine secretion, oxidative stress and platelet/coagulative activation identify non-alcoholic fatty liver disease among patients with familial combined hyperlipidemia and/or metabolic syndrome.
abstract: OBJECTIVE
  In patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion. Among FCHL or MS patients, hyperactivity of the ligand-receptor for advanced glycation-end-products (RAGE) pathway, as reflected by inadequate protective response by the endogenous secretory (es)RAGE, in concert with genetic predisposition, may identify those with NAFLD even before and regardless of MS.
  
  
  METHODS
  We cross-sectionally compared 60 patients with vs. 50 without NAFLD. Each group included patients with FCHL alone, MS alone, and FCHL plus MS.
  
  
  RESULTS
  NAFLD patients had significantly lower plasma esRAGE, IL-10 and adiponectin, and higher CD40 ligand, endogenous thrombin potential and oxidized LDL. The effects of MS plus FCHL were additive. The genotypic cluster including LOX-1 IVS4-14A plus ADIPO 45GG and 256 GT/GG plus IL-10 10-1082G, together with higher esRAGE levels highly discriminate FCHL and MS patients not developing NAFLD.
  
  
  CONCLUSIONS
  Among FCHL or MS patients, noncarriers of the protective genotypic cluster, with lower esRAGE and higher degree of atherothrombotic abnormalities coincide with the diagnosis of NAFLD. This suggests an interplay between genotype, adipokine secretion, oxidative stress and platelet/coagulative activation, accelerating NAFLD occurrence as a proxy for cardiovascular disease.
authors.affiliation: Department of Medicine and Aging, University of Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Clinical Pharmacology, University of Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Blardi
authors.affiliation: Division of Clinical Pathology, University Teaching Hospital of Siena, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Scapellato
authors.affiliation: Division of Hematology, University of Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.affiliation: Unit of Emergency Radiology, University Teaching Hospital of Siena, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Guazzi
authors.affiliation: Division of Clinical Pathology, University Teaching Hospital of Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Terzuoli
authors.affiliation: Division of Clinical Pathology, University Teaching Hospital of Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tabucchi
authors.affiliation: Division of Clinical Pathology, University Teaching Hospital of Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Silvietti
authors.affiliation: Division of Hematology, University of Siena, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Lucani
authors.affiliation: Preventive Medicine CIRAS, University of Siena, Italy.
authors.forename: Walter Renato
authors.initials: WR
authors.lastname: Gioffrè
authors.affiliation: Atherothrombosis Centre, University of Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Scarpini
authors.affiliation: Department of Medicine and Aging, University of Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fazio
authors.affiliation: Department of Medicine and Aging, University of Chieti, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
authors.affiliation: Division of Hematology, University of Siena, Italy; Atherothrombosis Centre, University of Siena, Italy. Electronic address: luca.puccetti@unisi.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Puccetti
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D023201:CD40 Ligand / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000378:metabolism* / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism
chemical_list: D054392:Adipokines; D052242:Adiponectin; C508609:IL10 protein, human; D008077:Lipoproteins, LDL; D000067759:Receptor for Advanced Glycation End Products; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D023201:CD40 Ligand; D013917:Thrombin
keywords: Acetaminophen (PubChem CID: 1983); Atherothrombosis; CD40/CD40L; Cholesterol (PubChem CID: 5997); FCHL; Insulin (PubChem CID: 70678557); Metabolic syndrome; NAFLD; Triglycerides (PubChem CID: 5460048); esRAGE