title: Chlamydia pneumoniae acute liver infection affects hepatic cholesterol and triglyceride metabolism in mice.
abstract: OBJECTIVE
  Chlamydia pneumoniae has been linked to atherosclerosis, strictly associated with hyperlipidemia. The liver plays a central role in the regulation of lipid metabolism. Since in animal models C. pneumoniae can be found at hepatic level, this study aims to elucidate whether C. pneumoniae infection accelerates atherosclerosis by affecting lipid metabolism.
  
  
  METHODS
  Thirty Balb/c mice were challenged intra-peritoneally with C. pneumoniae elementary bodies and thirty with Chlamydia trachomatis, serovar D. Thirty mice were injected with sucrose-phosphate-glutamate buffer, as negative controls. Seven days after infection, liver samples were examined both for presence of chlamydia and expression of genes involved in inflammation and lipid metabolism.
  
  
  RESULTS
  C. pneumoniae was isolated from 26 liver homogenates, whereas C. trachomatis was never re-cultivated (P < 0.001). C. pneumoniae infected mice showed significantly increased serum cholesterol and triglycerides levels compared both with negative controls (P < 0.001 and P = 0.0197, respectively) and C. trachomatis infected mice (P < 0.001). Liver bile acids were significantly reduced in C. pneumoniae compared to controls and C. trachomatis infected mice. In C. pneumoniae infected livers, cholesterol 7α-hydroxylase (Cyp7a1) and low-density lipoprotein receptor (Ldlr) mRNA levels were reduced, while inducible degrader of the low-density lipoprotein receptor (Idol) expression was increased. Hypertriglyceridemia was associated to reduced expression of hepatic carnitine palmitoyltransferase-1a (Cpt1a) and medium chain acyl-Coenzyme A dehydrogenase (Acadm). Pro-inflammatory cytokines gene expression was increased compared to negative controls. Conversely, in C. trachomatis infected animals, normal serum lipid levels were associated with elevated pro-inflammatory cytokines gene expression, linked to only a mild disturbance of lipid regulatory genes.
  
  
  CONCLUSIONS
  Our results indicate that C. pneumoniae mouse liver infection induces dyslipidemic effects with significant modifications of genes involved in lipid metabolism.
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Marangoni
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Fiorino
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Gilardi
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Aldini
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Scotti
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Nardini
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Foschi
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Donati
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università degli studi di Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Montagnani
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università degli studi di Bologna, Bologna, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cevenini
authors.affiliation: Dipartimento di Chimica "G. Ciamician", Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Franco
authors.affiliation: Dipartimento di Chimica "G. Ciamician", Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Roda
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address: maurizio.crestani@unimi.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Crestani
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cevenini
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000382:microbiology; D001647:Bile Acids and Salts / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002690:Chlamydia Infections / Q000150:complications / Q000382:microbiology*; D002692:Chlamydia trachomatis; D016993:Chlamydophila pneumoniae; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000737:chemistry; D007249:Inflammation; D007263:Infusions, Parenteral; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000382:microbiology; D017114:Liver Failure, Acute / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D016207:Cytokines; D008055:Lipids; D010710:Phosphates; D014280:Triglycerides; D018698:Glutamic Acid; D013395:Sucrose; D002784:Cholesterol; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase
keywords: Atherosclerosis; C. pneumoniae; Carnitine palmitoyltransferase; Cholesterol; Cholesterol 7α-hydroxylase; Inducible nitric oxide synthase; Interleukin-1β; Low-density lipoprotein receptor; Low-density lipoprotein receptor degrader; Medium chain acyl-CoA dehydrogenase