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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Immunity and Disease Prevention Research » Research » Publications at this Location » Publication #335534
Title: What causes high fat diet-induced postprandial inflammation: endotoxin or free fatty acids?

Author
item MO, ZHENZHEN - University Of California
item Huang, Shurong
item Baldiviez, Lacey
item Jandali, Ola
item BURNETT, DUSTIN - University Of California
item Bonnel, Ellen
item Woodhouse, Leslie
item Freytag, Tammy
item Domek, Joseph
item HOLGUIN, EVELYN - University Of California
item PEERSON, JANET - University Of California
item Stephensen, Charles
item Hwang, Daniel

Submitted to: United States-Japan Cooperative Program in Natural Resources (UJNR)
Publication Type: Abstract Only
Publication Acceptance Date: 9/14/2016
Publication Date: N/A
Citation: N/A

Interpretive Summary: Almost all reported studies supporting high fat diet induced endotoxemia as a cause for postprandial inflammation are based on the results of increased endotoxin concentrations in postprandial blood samples determined by Limulus Amebocyte Lysate (LAL) assay. The LAL assay has been approved by the United States FDA for the determination of endotoxins in parenterally delivered drugs for humans and animals, biological products and medical devices. However, some recent studies have raised serious questions about the reliability and accuracy of this assay for quantifying endotoxins in human blood. Therefore, we investigated whether high fat (60% saturated fat) meal increases the concentrations of endotoxin in postprandial plasma and leads to increased production of proinflammatory cytokines in human subjects. In addition, we investigated whether the concentration of plasma free fatty acids (FFA) is one of the determinants modulating postprandial inflammatory responses. our results suggest that the consensus proposition that high fat meals induce the absorption of endotoxin from the gut leading to metabolic endotoxemia would need more rigid re-evaluation. Based on the studies of ours and others, and critical reviews, we propose an alternative hypothesis (in addition to endotoxemia) that plasma FFAs may be one of determinants affecting postprandial inflammatory status.

Technical Abstract: Introduction High fat (saturated fat) diet has been generally used to induce tissue inflammation, insulin resistance and obesity in animal models. High fat diet can also induce postprandial inflammation in humans. Importantly, postprandial inflammation is linked to elevated cardiovascular and metabolic disease risk. How and when a high fat diet/meal induces postprandial inflammation remains unclear. Experimental results suggesting two competing mechanisms have been reported. One mechanism generally accepted is that high fat diet enhances the absorption of endotoxin from the gut leading to the activation of pattern recognition receptors including TLR2/4 and the production of proinflammatory gene products (so called metabolic endotoxemia) (1,2). The other mechanism implicated is that saturated fatty acids (instead of, or in addition to endotoxin) derived from the high fat diet induce inflammation by activating pattern recognition receptors leading to production of proinflammatory gene products. Almost all reported studies supporting high fat diet induced endotoxemia as a cause for postprandial inflammation are based on the results of increased endotoxin concentrations in postprandial blood samples determined by Limulus Amebocyte Lysate (LAL) assay. The LAL assay has been approved by the United States FDA for the determination of endotoxins in parenterally delivered drugs for humans and animals, biological products and medical devices. However, some recent studies have raised serious questions about the reliability and accuracy of this assay for quantifying endotoxins in human blood. Therefore, we investigated whether high fat (60% saturated fat) meal increases the concentrations of endotoxin in postprandial plasma and leads to increased production of proinflammatory cytokines in human subjects. In addition, we investigated whether the concentration of plasma free fatty acids (FFA) is one of the determinants modulating postprandial inflammatory responses.