Dietary oxidized fatty acids may enhance intestinal apolipoprotein A-I production.
Apolipoprotein (apo)A-I, the major protein component of HDL, is synthesized principally in the small intestine and liver. Recently we observed an increase in plasma apoA-I level in humans who were on an oxidized fat diet. To test whether oxidized fatty acids could affect apoA-I synthesis, we incubated day 4 (undifferentiated) and day 14 (differentiated) Caco-2 cells with varying concentrations of oxidized linoleic acid (ox-linoleic acid) (5, 10, and 25 microM) and unoxidized linoleic acid for 24 h. Ox-linoleic acid caused a dose-dependent increase in the levels of apoA-I protein in both differentiated and undifferentiated Caco-2 cells as assessed by ELISA and Western blot analysis. Whereas apoB production was not increased by ox-linoleic acid in both day 4 and day 14 Caco-2 cells. The mRNA expression for apoA-I paralleled the protein expression when measured by RT-PCR. We also found that both day 4 and day 14 Caco-2 cells did express peroxisomal proliferator-activated receptor-gamma (PPAR-gamma). mRNA and PPAR-gamma ligand could increase apoA-I secretion in these cells. Therefore we propose that the mechanism for the induction of apoA-I might include PPAR-gamma for which oxidized fatty acid is a ligand.
Rong
Rong
R
Department of Gynecology and Obstetrics and Nutrition and Health Sciences Program, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ramachandran
Sumathi
S
Penumetcha
Meera
M
Khan
Nadya
N
Parthasarathy
Sampath
S
D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D018938:Caco-2 Cells / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D019787:Linoleic Acid / Q000378:metabolism*; D008041:Linoleic Acids / Q000494:pharmacology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D004042:Dietary Fats, Unsaturated; D008041:Linoleic Acids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C042835:13-hydroxylinoleic acid; D019787:Linoleic Acid