The impact of dietary fatty acids on macrophage cholesterol homeostasis.
The impact of dietary fatty acids in atherosclerosis development may be partially attributed to their effect on macrophage cholesterol homeostasis. This process is the result of interplay between cholesterol uptake and efflux, which are permeated by inflammation and oxidative stress. Although saturated fatty acids (SAFAs) do not influence cholesterol efflux, they trigger endoplasmic reticulum stress, which culminates in increased lectin-like oxidized LDL (oxLDL) receptor (LOX1) expression and, consequently, oxLDL uptake, leading to apoptosis. Unsaturated fatty acids prevent most SAFAs-mediated deleterious effects and are generally associated with reduced cholesterol efflux, although α-linolenic acid increases cholesterol export. Trans fatty acids increase macrophage cholesterol content by reducing ABCA-1 expression, leading to strong atherosclerotic plaque formation. As isomers of conjugated linoleic acid (CLAs) are strong PPAR gamma ligands, they induce cluster of differentiation (CD36) expression, increasing intracellular cholesterol content. Considering the multiple effects of fatty acids on intracellular signaling pathways, the purpose of this review is to address the role of dietary fat in several mechanisms that control macrophage lipid content, which can determine the fate of atherosclerotic lesions.
Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, Sao Paulo, Brazil.
Milessa da Silva
Mda S
Afonso
Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, Sao Paulo, Brazil.
Gabriela
G
Castilho
Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, Sao Paulo, Brazil.
Maria Silvia Ferrari
MS
Lavrador
Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, Sao Paulo, Brazil.
Marisa
M
Passarelli
Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, Sao Paulo, Brazil.
Edna Regina
ER
Nakandakare
Endocrinology Service from of the Clinical Hospital of the University of São Paulo, Sao Paulo, Brazil.
Simão Augusto
SA
Lottenberg
Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, Sao Paulo, Brazil. Electronic address: amlottenberg@uol.com.br.
Ana Maria
AM
Lottenberg
D002784:Cholesterol / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism
D004041:Dietary Fats; D005227:Fatty Acids; D002784:Cholesterol
Cholesterol efflux; Cholesterol uptake; Fatty acids; Macrophage