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United States Department of Agriculture

Agricultural Research Service

Research Project: DIET AND BIOMARKERS OF CARDIOVASCULAR HEALTH

Location: Human Nutrition Research Center on Aging

Title: Thp-1 Macrophage Lipid Accumulation Unaffected by Fatty Acid Double Bond Geometric Or Positional Configuration

Authors
item Dillard, Alice -
item Matthan, Nirupa -
item Lichtenstein, Alice -

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 2, 2011
Publication Date: September 16, 2011
Citation: Dillard, A., Matthan, N., Lichtenstein, A. 2011. THP-1 macrophage lipid accumulation unaffected by fatty acid double bond geometric or positional configuration. Nutrition Research. 31(8):625-630.

Interpretive Summary: Dietary fatty acid type can alter atherosclerotic lesion progression and macrophage lipid accumulation. Macrophage lipid accumulation is important because this process is directly related to lesion progression. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration, cis and trans fatty acids, or double bond position, omega-3 and omega-6 fatty acids, alter atherosclerotic lesion progression. The objective of this study was to evaluate the suitability of using Tamm-Horsfall protein 1 (THP-1) macrophages as a model for human monocytes/macrophages to address this issue. Our hypothesis was that THP-1 macrophages pretreated with omega-3 fatty acids or fatty acid containing a cis double bond would accumulate less lipid, particularly cholesteryl ester, compared with omega-6 fatty acids or a fatty acid containing a trans double bond, respectively. THP-1 monocytes were differentiated into macrophages and then incubated with the fatty acids of interest for 2-days. At the end of that period there was an increase in intracellular lipid in response to all the fatty acids assessed, and the response was similar among the fatty acids. The increase in lipid accumulation was primarily triglyceride and to a lesser extent cholesterol, primarily free rather than esterified cholesterol. These data suggest that free fatty acids bound to bovine serum albumin, regardless of double-bond geometric or positional configuration, induce triglyceride accumulation but had only a modest effect on cholesterol accumulation in THP-1 macrophages. The cells appeared to respond similarly to the assessed fatty acids in terms of amount and type of lipid accumulated. Hence, the THP-1 cell line was not appropriate to test the hypotheses of interest.

Technical Abstract: Dietary fatty acid type alters atherosclerotic lesion progression and macrophage lipid accumulation. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration alter arterial lipid accumulation. The objective of this study was to evaluate the suitability of using Tamm-Horsfall protein 1 (THP-1) macrophages as a model for human monocytes/macrophages to address this issue. Our hypothesis was that THP-1 macrophages pretreated with omega-3 polyunsaturated fatty acids (PUFA) or fatty acid containing a cis double bond would accumulate less lipid, particularly cholesteryl ester, compared with omega-6 polyunsaturated fatty acids or a fatty acid containing a trans double bond, respectively. THP-1 monocytes were differentiated into macrophages and then incubated with fatty acids for 48 hours. There was an increase in intracellular lipid in response to all the fatty acids assessed, and by response was similar among the fatty acids. The increase in lipid accumulation was contributed to triglyceride and to a lesser extent cholesterol, primarily free cholesterol. These data suggest that free fatty acids bound to bovine serum albumin, regardless of double-bond geometric or positional configuration, induce triglyceride accumulation but had only a modest effect on cholesterol accumulation in THP-1 macrophages. The cells appeared to respond similarly to the assessed fatty acids in terms of amount and type of lipid accumulated. Hence, the THP-1 cell line was not appropriate to test the hypotheses of interest.

Last Modified: 7/28/2014
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