|Kabagambe, Edmond - UNIVERSITY OF ALABAMA|
|Tsai, Michael - UNIVERSITY OF MINNESOTA|
|Borecki, Ingrid - WASHINGTON UNIVERSITY|
|Hopkins, Paul - UNIVERSITY OF UTAH|
|Arnett, Donna - UNIVERSITY OF ALABAMA|
Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 1, 2008
Publication Date: April 1, 2009
Citation: Kabagambe, E.K., Ordovas, J.M., Tsai, M.Y., Borecki, I.B., Hopkins, P.N., Arnett, D.K. 2009. Smoking, inflammatory patterns, and postprandial hypertriglyceridemia. Atherosclerosis. 203(2):633-639. Interpretive Summary: Smoking is associated with increased risk for multiple diseases, including cardiovascular diseases (CVD). Blood lipid concentrations are known risk factors for CVD, especially those circulating following a fat-rich meal (postprandial lipemia, PPL). Inflammation and insulin resistance are potential “drivers” for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPL. For this purpose, we investigated men and women in the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study in Utah and Minnesota. Analysis of our data reveals an impaired metabolism of dietary fat among smokers and suggests that mechanisms other than inflammation or insulin resistance may explain the observed hypertriglyceridemia among smokers. In summary, our study confirms impaired dietary fat metabolism among smokers and shows that this association is not due to inflammation, insulin resistance or central obesity, which are independently associated with increased postprandial hypertriglyceridemia. We speculate that oxidative stress due to smoke bi-products could down-regulate key lipid-metabolizing enzymes and that smoke bi-products could reduce availability of beneficial fatty acids and pharmacologic products such as fibrates, leading to impaired fat metabolism among current smokers.
Technical Abstract: Background: Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential "drivers" for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT. Methods: Men and women in the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study in Utah and Minnesota (n=1036, age 49+/-16 y) were included. Each study participant was asked to suspend use of lipid-lowering drugs for three weeks and was given a high-fat milkshake (83% fat and 700 kcal/m^2). Triglyceride concentrations at 0, 3.5 and 6 hr after the fat load were measured. Inflammatory markers were measured at baseline. Principal component analysis was used to derive inflammatory patterns from individual inflammatory markers (CRP, IL-2, IL-6, TNF-alpha and MCP-1). Insulin resistance (IR) was estimated using the HOMA equation. Repeated measures-ANOVA was used for analyses. Results: Two inflammatory patterns, namely CRP-IL6 pattern and MCP-1-TNF-alpha pattern, were derived. We found significant main (smoking and time) and interaction (smoking*time) effects (P<0.01) for triglycerides. The multivariate-adjusted mean log-transformed triglyceride concentrations for never, past and current smokers were 4.76+/-0.03, 4.70+/-0.04 and 4.81+/-0.07at 0 hr; 5.35+/-0.03, 5.39+/-0.04 and 5.59+/-0.07 at 3.5 hr; and 5.18+/-0.03, 5.25+/-0.04 and 5.42+/-0.07 at 6 hr after the fat load, respectively. Smoking remained significant after adjusting for HOMA-IR and/or inflammatory patterns which showed independent associations with PPT (P<0.05). Conclusion: These data confirm impaired metabolism of dietary fat among smokers and suggest that mechanisms other than inflammation or insulin resistance may explain the observed hypertriglyceridemia among smokers.