Journal Name:
Am. J. Clin. Nutr.

Article Title:
Postprandial effect of n–3 polyunsaturated fatty acids on apolipoprotein B–containing lipoproteins and vascular reactivity in type 2 diabetes.

Date Written:
2007

Volume:
85

Number:
0

Page:
369

Author(s):
Hilpert, K.F.; West, S.G.; Kris-Etherton, P.M.; Hecker, K.D.; Simpson, N.M.; Alaupovic, P.

Article:
There are 2 principal classes of lipoproteins, one of which is characterized by apolipoprotein A and by apolipoprotein B (apo B). The apo A–containing lipoproteins include 3 major subclasses [lipoprotein A-I (LpA-I), lipoprotein A-I and AII (LpA-I:A-II), and lipoprotein A-II (LpA-II)], and the apo B–containing lipoproteins consist of 5 major subclasses [lipoprotein B (LpB); lipoprotein B and C (LpB:C); lipoprotein B and E (LpB:E); lipoprotein B, C, and E (LpB:C:E); and lipoprotein A-II, B, C, D, and E (LpA-II:B:C:D: E)].
Apo A–containing lipoproteins overlap within the HDL-density range, and the apo B–containing lipoproteins overlap within the VLDL-, IDL-1, and LDL-density ranges. Apo A– and apo B–containing lipoprotein subclasses differ from each other not only by their apolipoprotein composition, but also by their specific metabolic properties.
Individual apo A–containing lipoprotein subclasses differ in their relative antiatherogenic capacities and apo B–containing lipoprotein subclasses differ in their atherogenic capacities. The relative atherogenic potential of the LpB:C subclass may be more pronounced than that of other apo B–containing lipoproteins. Although diet plays a crucial role in modulating lipid metabolism, little is known of its effects on apolipoprotein-defined lipoprotein subclasses.
The acute effects of individual fatty acids on apolipoprotein B (apo B)–containing lipoproteins in adults with type 2 diabetes (n=15) was assessed. Three meals were administered in a randomized, double-blind, crossover design. Treatments contained skim milk and 50 g fat from high–oleic acid safflower and canola oils (monounsaturated fatty acid; MUFA), MUFA, 3.5 g alpha-linolenic acid (ALA; MUFA+ALA) from high-ALA canola oil, or MUFA + 4.0 g both eicosa¬pentaenoic acid (EPA) and docosahexaenoic acid (DHA; MUFA+ EPA/DHA) from sardine oil. Apo B, LpB, LpB:C, LpB:E + LpB: C:E, and LpA-II:B:C:D:E were measured at baseline and 2 and 4 h after the meal. Flow-mediated dilation was measured at baseline and 4 h after the meal.
The present study provides the first description of the effects of unsaturated fatty acids on individual apo B–containing lipoprotein subclasses in the postprandial state. Apo B–containing lipoproteins were the focus of this study because of their atherogenic potential and their increased concentrations in triacylglycerol-rich lipoproteins in the postprandial state.
The treatments significantly increased apo B and LpB post¬prandially but the magnitude of the changes did not differ significantly between the treatments. The postprandial change in LpB:C was 23% lower after MUFA + EPA/DHA than after MUFA. MUFA+ ALA attenuated the increase in LpA-II:B:C:D:E in those with high triacylglycerols but was the only treatment to significantly increase this particle in those with low triacylglycerols. Examination of change scores did not reveal the source of the interaction of treatment and time for LpB:E + LpB:C:E. Furthermore, the subjects with the largest increases in LpB:C exhibited the largest impairment in endothelial function. The results suggest that unsaturated fatty acids dif¬ferentially affect concentrations of apo B–containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA +EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function.
In a previous report on the same subject cohort, only subjects with high fasting triacylglycerol had improved endothelial function when 7–8% of the oleic acid fat blend was replaced with n-3 fatty acids from canola or sardine oil. Thus, a goal of the present study was to examine whether changes in apo B–containing lipoprotein subclasses were associated with significant changes in vascular endothelial function and triacylglycerol status. This is important, because endothelial dysfunction is common in patients with type 2 diabetes and is considered a key initiating step in the development of atherosclerosis.
The results suggest that unsaturated fatty acids differentially affect concentrations of apo B–containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA from canola oil plus EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function.
These results show that all treatments had similar effects on total apo B but different effects on individual apo B–containing particles in adults with type 2 diabetes.A meal containing 2.8 g EPA and 1.2 g DHA attenuated the postprandial rise in LpB:C seen with the control treatment. Furthermore, the postprandial change in LpB:C was shown to be a significant predictor of the change in FMD after the meal. The subjects with the largest postprandial increases in LpB:C exhibited the smallest improvements in endothelium-dependent vasodilation. This finding has provided additional evidence for the potentially marked atherogenic character of the LpB:C subclass. According to density-defined lipoproteins, cholesterol-rich LDL are generally considered to have the highest atherogenic capacity, followed, in decreasing order of atherogenicity, by intact or partially delipidized triacylglycerol-rich IDL, small VLDL, and large VLDL. Although cholesterol-rich LpB and LpB:E subclasses occur mainly, but not exclusively, in LDL density ranges and triacylglycerol-rich LpB:C, LpB:C:E,and LpA-II:B:C:D:E in VLDL and IDL density ranges, these 2 groups of lipoprotein subclasses overlap to varying degrees in most, if not all, segments of the density gradient.
Although the contribution of specific apo B–containing lipoprotein (ie, LpB:C) to the risk of CVD has yet to be determined, these preliminary findings suggest that changing the fatty acid profile of a meal has significant acute effects on specific apo B–containing lipoprotein metabolism, similar to the effects observed with cholesterol-lowering drugs. Because of the extent of time spent in the postabsorptive state, changes that occur in apo B–containing lipoprotein (ie, LpB:C) in the postprandial period are important.
Further studies will be necessary to identify the diet that is most effective postprandially, as well as chronically, with respect to CVD risk reduction. Although much is known about the effects of the habitual diet on CVD risk, the present study showed that there are opportunities to target the postprandial period to further reduce heart disease, especially in persons with diabetes.

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