C-reactive protein levels are inversely correlated with the apolipoprotein B-48-containing triglyceride-rich lipoprotein production rate in insulin resistant men.

The pro-inflammatory state and elevated plasma levels of post-prandial triglycerides (TG) are associated with increased cardiovascular disease risk. Recent studies suggested that the increase in the production rate of post-prandial lipoproteins observed in patients with insulin resistance (IR) may be caused, at least in part, by the dysregulation of intestinal insulin sensitivity triggered by inflammation. OBJECTIVE: The objective of the present study was to evaluate the association between IR, plasma C-reactive protein (CRP) levels and the kinetics of TG-rich lipoprotein (TRL) containing apolipoprotein (apo) B-48 in a large sample of insulin sensitive (IS) and IR men. METHODS: The in vivo kinetics of TRL apoB-48 were measured in 151 men following a primed-constant infusion of l-[5,5,5-D3]leucine. IR subjects (n=91) were characterized by fasting TG levels ≥1.5mmol/L and an index of homeostasis model assessment of IR (HOMA-IR)≥2.5 or type 2 diabetes, while IS subjects (n=24) were characterized by an HOMA-IR index <2.5 and TG levels <1.5mmol/L. RESULTS: IR subjects had higher TRL apoB-48 production rate (+202%; P<0.0001) and CRP levels (+51%; P=0.01) than IS subjects. TRL apoB-48 production rate and CRP levels were inversely correlated in IR subjects (r=-0.32; P=0.002). IR subjects with CRP levels above the median (2.20mg/L) had lower TRL apoB-48 production rate than IR subjects with CRP levels below the median (Δ=-24%; P<0.05). CONCLUSION: Our results confirm that IR is associated with increased TRL apoB-48 secretion and suggest that a higher inflammatory status is associated with decreased TRL apoB-48 secretion among IR subjects.

A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study.

BACKGROUND: To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. OBJECTIVES: We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. DESIGN: In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. RESULTS: Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). CONCLUSIONS: DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.