title: Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation.
abstract: Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: milessafonso@gmail.com.
authors.forename: Milessa Silva
authors.initials: MS
authors.lastname: Afonso
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: mariasilviaferrari@yahoo.com.br.
authors.forename: Maria Silvia Ferrari
authors.initials: MS
authors.lastname: Lavrador
authors.affiliation: Emergency Care Research Unit Laboratory (LIM51), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: mkoike2011@gmail.com.
authors.forename: Marcia Kiyomi
authors.initials: MK
authors.lastname: Koike
authors.affiliation: Laboratory of Nutritional Genomics (LabGeN), School of Applied Science, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil. Electronic address: dcintra@yahoo.com.
authors.forename: Dennys Esper
authors.initials: DE
authors.lastname: Cintra
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: fabianaferreira1@hotmail.com.
authors.forename: Fabiana Dias
authors.initials: FD
authors.lastname: Ferreira
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: valeriasutti@gmail.com.
authors.forename: Valeria Sutti
authors.initials: VS
authors.lastname: Nunes
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: ga.castilho@gmail.com.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Castilho
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, Brazil. Electronic address: lagio@usp.br.
authors.forename: Luiz Antonio
authors.initials: LA
authors.lastname: Gioielli
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: rebombo@terra.com.br.
authors.forename: Renata
authors.initials: R
authors.lastname: Paula Bombo
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: catanozi@usp.br.
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.affiliation: Laboratory of Cell Biology (LIM59), Department of Pathology, Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: elia@usp.br.
authors.forename: Elia Garcia
authors.initials: EG
authors.lastname: Caldini
authors.affiliation: Laboratory of Cell Biology (LIM59), Department of Pathology, Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: nilsa@usp.br.
authors.forename: Nilsa Regina
authors.initials: NR
authors.lastname: Damaceno-Rodrigues
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: mpassere@usp.br.
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil. Electronic address: enakonda@usp.br.
authors.forename: Edna Regina
authors.initials: ER
authors.lastname: Nakandakare
authors.affiliation: Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil; Albert Einstein Faculty of Health Sciences, São Paulo, Brazil. Electronic address: ana.lottenberg@hc.fm.usp.br.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Lottenberg
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004951:Esterification; D018507:Gene Expression Regulation, Developmental; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019308:Palmitic Acid / Q000009:adverse effects* / Q000737:chemistry; D011897:Random Allocation; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013229:Stearic Acids / Q000009:adverse effects / Q000737:chemistry; D044242:Trans Fatty Acids / Q000009:adverse effects / Q000737:chemistry; D014280:Triglycerides / Q000009:adverse effects* / Q000737:chemistry; D014886:Weaning
chemical_list: D015415:Biomarkers; D016207:Cytokines; D011973:Receptors, LDL; D013229:Stearic Acids; D044242:Trans Fatty Acids; D014280:Triglycerides; D019308:Palmitic Acid; C031183:stearic acid; D002784:Cholesterol
keywords: Atherosclerosis; Diet; Interesterified fat; Lipoprotein metabolism; Mice; Trans fat