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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #348651

Title: Putative inflammatory effects of saturated fatty acids: Experimental confounders and context-specificity

item ONO-MOORE, KIKUMI - Arkansas Children'S Nutrition Research Center (ACNC)
item MICHAEL, BLACKBURN - Arkansas Children'S Nutrition Research Center (ACNC)
item Ferruzzi, Mario

Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: 10/31/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Based primarily on cell culture experiments, long-chain saturated fatty acids (SFAs) are thought to promote inflammation and contribute to metabolic dysfunction through toll-like receptor activation. This, in turn, has been implicated in contributing to chronic low-grade inflammation associated with obesity-associated insulin resistance and cardiometabolic disease. However, confidence in these assertions is tempered by potential confounding variables in cell culture studies. For instance, experiments typically require long-chain fatty acid carriers (e.g. BSA) or solvents (e.g. ethanol): yet, BSA can induce inflammation and ethanol is a known cytotoxin. To ascertain if these factors influence SFA-associated inflammation, we first measured responses of RAW264.7 monocyte/macrophages and C2C12 myotubes to various BSA and ethanol conditions. Even in the absence of palmitate, BSA preparations activated, whereas 0.5-1.0% ethanol inhibited, RAW264.7 TNF-alpha release. Ethanol modestly increased IL-6 secretion in C2C12 myotubes. Using a low-inflammation BSA source and no ethanol, ~24 hr sodium palmitate treatment (up to 600 um) failed to trigger RAW264.7 TNF-alpha release, and in fact significantly dampened BSA-induced inflammation. In C2C12 myotubes, only high palmitate concentrations (500-600 um) elicited IL-6 secretion, and acute palmitate (200 or 500 µM) did not activate MAP-kinase pathways above that of fresh media alone. These results highlight the importance of experimental conditions in studies exploring SFA inflammation and cell stress effects. The limited (or even anti-inflammatory) effects of palmitate that we observed indicate that immunomodulatory effects of SFAs are context-specific. Results from the literature on the effects of fat delivery in vivo (by "mixed meal" do not support the idea that SFA-rich preparations are, by definition, pro-inflammatory. Infusion studies have shown that fats can elicit insulin resistance acutely, but this cannot be attributed specifically to SFA. Thus, caution is needed when interpreting the literature related to putative pro-inflammatory effects of SFA.