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p38 MAPK protects human monocytes from postprandial triglyceride-rich lipoprotein-induced toxicity.

The Journal of nutrition (2013-03-15)
Sergio Lopez, Sara Jaramillo, Lourdes M Varela, Almudena Ortega, Beatriz Bermudez, Rocio Abia, Francisco J G Muriana
ABSTRACT

Postprandial triglyceride (TG)-rich lipoproteins (TRLs) transport dietary fatty acids through the circulatory system to satisfy the energy and structural needs of the tissues. However, fatty acids are also able to modulate gene expression and/or induce cell death. We investigated the underlying mechanism by which postprandial TRLs of different fatty acid compositions can induce cell death in human monocytes. Three types of dietary fat [refined olive oil (ROO), high-palmitic sunflower oil (HPSO), and butter] with progressively increasing SFA:MUFA ratios (0.18, 0.41, and 2.08, respectively) were used as a source of postprandial TRLs (TRL-ROO, TRL-HPSO, and TRL-BUTTER) from healthy men. The monocytic cell line THP-1 was used as a model for this study. We demonstrated that postprandial TRLs increased intracellular lipid accumulation (31-106%), reactive oxygen species production (268-349%), DNA damage (133-1467%), poly(ADP-ribose) polymerase 1 (800-1710%) and caspase-3 (696-1244%) activities, and phosphorylation of c-Jun NH2-terminal kinase (JNK) (54 kDa, 141-288%) and p38 (24-92%). These effects were significantly greater with TRL-BUTTER, and TRL-ROO did not induce DNA damage, DNA fragmentation, or p38 phosphorylation. In addition, blockade of p38, but not of JNK, significantly decreased intracellular lipid accumulation and increased cell death in postprandial TRL-treated cells. These results suggest that in human monocytes, p38 is involved in survival signaling pathways that protect against the lipid-mediated cytotoxicity induced by postprandial TRLs that are abundant in saturated fatty acids.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Olive oil, highly refined, low acidity
Sigma-Aldrich
Sunflower seed oil from Helianthus annuus
Sigma-Aldrich
Sunflower seed oil from Helianthus annuus, tested according to Ph. Eur.
Sigma-Aldrich
Olive oil, tested according to Ph. Eur.
Supelco
Olive oil, analytical standard
Supelco
Sunflower seed oil, analytical standard
Sigma-Aldrich
Sunflower oil, Certified organic (NOP)
Sigma-Aldrich
PARP-1 human, recombinant, expressed in E. coli

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