Is palmitate truly proinflammatory? Experimental confounders and context-specificity

American Journal of Physiology. Endocrinology and Metabolism
Kikumi D Ono-MooreSean H Adams

Abstract

Based primarily on cell culture results, saturated fatty acids (SFAs) are proposed to promote inflammation and contribute to metabolic dysfunction through Toll-like receptor activation. Studies are often complicated by a requirement for carriers (e.g., BSA) or solvents (e.g., ethanol) to increase SFA solubility. To ascertain whether these factors influence interpretations of SFA-associated inflammation activity, we measured responses of RAW264.7 monocyte/macrophages and C2C12 myotubes to various BSA, ethanol, and cyclodextrin (alternative FA carrier) conditions. Fatty acid-free, low-endotoxin BSA preparations (0.33% to 2% wt/vol) activated whereas 0.5-1.0% ethanol inhibited RAW264.7 TNFα release. Ethanol modestly increased IL-6 secretion in C2C12 myotubes. Cyclodextrins (0.3-6.0 mM) were tested as alternative carriers of palmitate, but their usefulness was limited due to toxicity and solubility issues. Using a lower-inflammation BSA source and no ethanol, ∼24-h sodium palmitate treatment (≤600 µM) failed to trigger RAW264.7 TNFα release and, in fact, significantly dampened BSA-induced inflammation by >50%. In C2C12 myotubes, only high palmitate concentrations (500-600 µM) elicited IL-6 secretion (>2.5-fold increase). Acute palm...Continue Reading

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Citations

May 28, 2020·American Journal of Physiology. Endocrinology and Metabolism·Michael L BlackburnSean H Adams
Sep 27, 2019·Advances in Nutrition·Kristin M HirahatakeSean H Adams
Oct 15, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Natticha SumneangNipon Chattipakorn
Jun 27, 2019·Neuroscience Letters·Q LeyrolleA Nadjar

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Methods Mentioned

BETA
PCR
ELISA
Protein Assay

Software Mentioned

Graphpad Prism

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