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Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans.

Sergeant S, Ruczinski I, Ivester P, Lee TC, Morgan TM, Nicklas BJ, Mathias RA, Chilton FH - Br. J. Nutr. (2015)

Bottom Line: This reversal pattern was replicated in serum samples from both human cohorts.The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data.These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids.

View Article: PubMed Central - PubMed

Affiliation: 1Center for Botanical Lipids and Inflammatory Disease Prevention,Wake Forest School of Medicine,Medical Center Blvd,Winston-Salem,NC 27157,USA.

ABSTRACT
Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

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Related in: MedlinePlus

Predicted relationships between blood lipids and selected PUFA (Diet, Exercise, Metabolism and Obesity in Older Women cohort). Sample correlations between cholesterol-containing blood lipids (TAG, total cholesterol (TC), LDL, HDL, ratio of TC:HDL-cholesterol) and selected serum fatty acids (oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA), α-linolenic acid (ALA), DHA), using both measured fatty acid concentrations (mg/dl; ‘mass observed’) and percentage of total data (‘% observed’). Also shown are the predicted correlations between blood lipids and percentage of total (‘% predicted’). Positive v. negative correlations are highlighted by v.  cells, respectively.
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fig4: Predicted relationships between blood lipids and selected PUFA (Diet, Exercise, Metabolism and Obesity in Older Women cohort). Sample correlations between cholesterol-containing blood lipids (TAG, total cholesterol (TC), LDL, HDL, ratio of TC:HDL-cholesterol) and selected serum fatty acids (oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA), α-linolenic acid (ALA), DHA), using both measured fatty acid concentrations (mg/dl; ‘mass observed’) and percentage of total data (‘% observed’). Also shown are the predicted correlations between blood lipids and percentage of total (‘% predicted’). Positive v. negative correlations are highlighted by v. cells, respectively.

Mentions: In addition to TAG, circulating fatty acids also reside in other circulating complex lipids including LDL, HDL and TC, which have been utilised as disease biomarkers. Fig. 4 summarises the associations between cholesterol-containing blood lipids and selected serum fatty acids (OA, LA, ARA, ALA, DHA) using both concentration (mmol/l) and percentage of total data. With the exception of HDL, the (Pearson’s) correlations of blood lipids with fatty acid concentration (mass) were positive (blue cells), whereas the correlations with percentage of total data were either positive (blue) or negative (pink). Importantly, the mathematically predicted association values for percentage of total were nearly identical (in both magnitude and direction) to those observed for percentage of total fatty acids. As was the case for TAG, the associations of TC, LDL, HDL and the TC:HDL ratio with OA were consistent for both expression methods. Like LA, the long-chain n-6 and n-3 PUFA (ARA and DHA, respectively) showed a reversal in the direction of associations using the percentage of total fatty acid expression for TAG, TC, LDL and the ratio of TC:HDL-cholesterol. In contrast, associations with HDL tended not to undergo a change in direction between the fatty acid expression methods, except for LA, for which the associations were not very robust. The associations between TAG and DHA were comparable (for mass observed, positive; percentage of total observed and predicted, negative) to that for the association between TAG and EPA+DHA (mass observed, 0·30; percentage of total observed, −0·21, and predicted, −0·19). Nearly identical results, both in the robustness and direction of correlations, were observed in the replication data set (online Supplementary Fig. S2). Overall, the mathematically modelling technique appears to be useful for predicting a reversal in the direction on associations between fatty acid expression methods and blood lipids.Fig. 4


Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans.

Sergeant S, Ruczinski I, Ivester P, Lee TC, Morgan TM, Nicklas BJ, Mathias RA, Chilton FH - Br. J. Nutr. (2015)

Predicted relationships between blood lipids and selected PUFA (Diet, Exercise, Metabolism and Obesity in Older Women cohort). Sample correlations between cholesterol-containing blood lipids (TAG, total cholesterol (TC), LDL, HDL, ratio of TC:HDL-cholesterol) and selected serum fatty acids (oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA), α-linolenic acid (ALA), DHA), using both measured fatty acid concentrations (mg/dl; ‘mass observed’) and percentage of total data (‘% observed’). Also shown are the predicted correlations between blood lipids and percentage of total (‘% predicted’). Positive v. negative correlations are highlighted by v.  cells, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697295&req=5

fig4: Predicted relationships between blood lipids and selected PUFA (Diet, Exercise, Metabolism and Obesity in Older Women cohort). Sample correlations between cholesterol-containing blood lipids (TAG, total cholesterol (TC), LDL, HDL, ratio of TC:HDL-cholesterol) and selected serum fatty acids (oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA), α-linolenic acid (ALA), DHA), using both measured fatty acid concentrations (mg/dl; ‘mass observed’) and percentage of total data (‘% observed’). Also shown are the predicted correlations between blood lipids and percentage of total (‘% predicted’). Positive v. negative correlations are highlighted by v. cells, respectively.
Mentions: In addition to TAG, circulating fatty acids also reside in other circulating complex lipids including LDL, HDL and TC, which have been utilised as disease biomarkers. Fig. 4 summarises the associations between cholesterol-containing blood lipids and selected serum fatty acids (OA, LA, ARA, ALA, DHA) using both concentration (mmol/l) and percentage of total data. With the exception of HDL, the (Pearson’s) correlations of blood lipids with fatty acid concentration (mass) were positive (blue cells), whereas the correlations with percentage of total data were either positive (blue) or negative (pink). Importantly, the mathematically predicted association values for percentage of total were nearly identical (in both magnitude and direction) to those observed for percentage of total fatty acids. As was the case for TAG, the associations of TC, LDL, HDL and the TC:HDL ratio with OA were consistent for both expression methods. Like LA, the long-chain n-6 and n-3 PUFA (ARA and DHA, respectively) showed a reversal in the direction of associations using the percentage of total fatty acid expression for TAG, TC, LDL and the ratio of TC:HDL-cholesterol. In contrast, associations with HDL tended not to undergo a change in direction between the fatty acid expression methods, except for LA, for which the associations were not very robust. The associations between TAG and DHA were comparable (for mass observed, positive; percentage of total observed and predicted, negative) to that for the association between TAG and EPA+DHA (mass observed, 0·30; percentage of total observed, −0·21, and predicted, −0·19). Nearly identical results, both in the robustness and direction of correlations, were observed in the replication data set (online Supplementary Fig. S2). Overall, the mathematically modelling technique appears to be useful for predicting a reversal in the direction on associations between fatty acid expression methods and blood lipids.Fig. 4

Bottom Line: This reversal pattern was replicated in serum samples from both human cohorts.The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data.These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids.

View Article: PubMed Central - PubMed

Affiliation: 1Center for Botanical Lipids and Inflammatory Disease Prevention,Wake Forest School of Medicine,Medical Center Blvd,Winston-Salem,NC 27157,USA.

ABSTRACT
Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

Show MeSH
Related in: MedlinePlus