Chlamydia pneumoniae acute liver infection affects hepatic cholesterol and triglyceride metabolism in mice Antonella Marangoni a, 3 , Erika Fiorino b, 3 , Federica Gilardi b, 1 , 3 , Rita Aldini c , Elena Scotti b, 2 , Paola Nardini a , Claudio Foschi a , Manuela Donati a , Marco Montagnani d , Monica Cevenini d , Placido Franco e , Aldo Roda e , Maurizio Crestani b, *, 3 , Roberto Cevenini a, 3 a Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Universit a degli Studi di Bologna, Bologna, Italy b Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit a degli Studi di Milano, Milano, Italy c Dipartimento di Farmacia e Biotecnologie, Universit a degli Studi di Bologna, Bologna, Italy d Dipartimento di Scienze Mediche e Chirurgiche, Universit a degli studi di Bologna, Bologna, Italy e Dipartimento di Chimica “G. Ciamician”, Universit a degli Studi di Bologna, Bologna, Italy article info Article history: Received 6 November 2014 Received in revised form 15 May 2015 Accepted 25 May 2015 Available online 3 June 2015 Keywords: C. pneumoniae Cholesterol Atherosclerosis Cholesterol 7a-hydroxylase Low-density lipoprotein receptor Low-density lipoprotein receptor degrader Carnitine palmitoyltransferase Medium chain acyl-CoA dehydrogenase Interleukin-1b Inducible nitric oxide synthase abstract Objective: Chlamydia pneumoniae has been linked to atherosclerosis, strictly associated with hyperlip- idemia. 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 ¼ 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 7a- 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. Hyper- triglyceridemia 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. Conclusion: Our results indicate that C. pneumoniae mouse liver infection induces dyslipidemic effects with significant modifications of genes involved in lipid metabolism. © 2015 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Atherosclerosis is a multifactorial inflammatory process of ves- sels and it is strongly associated with abnormal levels of circulating lipids. Recent appreciation of atherosclerosis as a chronic inflam- matory disease [1,2] has rejuvenated efforts to examine the possible role of infectious agents in the etiology of this disorder [3]. The association between infection and atherosclerosis has been * Corresponding author. Laboratorio “Giovanni Galli” di Biochimica e Biologia Molecolare del Metabolismo e Spettrometria di Massa, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit a degli Studi di Milano, via Balzaretti, 9 e 20133 Milano, Italy. E-mail address: maurizio.crestani@unimi.it (M. Crestani). 1 Present address: University of Lausanne, Center for Integrative Genomics, 1015 Lausanne, Switzerland. 2 Present address: Swiss Federal Institute of Technology Zurich, Institute of Molecular Health Sciences, 8093 Zurich, Switzerland. 3 These authors contributed equally to this work. Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis http://dx.doi.org/10.1016/j.atherosclerosis.2015.05.023 0021-9150/© 2015 Elsevier Ireland Ltd. All rights reserved. Atherosclerosis 241 (2015) 471e479