ACTH reduces the rise in ApoB-48 levels after fat intake

It has been repeatedly demonstrated that ACTH administration lowers plasma lipid concentrations in man. The present study was designed to test the hypothesis, based on observations of decreased apolipoprotein B (ApoB) synthesis and secretion in vitro, that ACTH administration inhibits the postprandial output of ApoB in man. Therefore, we studied the response to a fat-rich meal supplemented with Vitamin A in eight healthy volunteers, who underwent this test without premedication, after 4 days administration of ACTH, and after 4 days administration of a glucocorticoid (betamethasone). As expected, fasting plasma levels of low-density lipoproteins (LDL)-cholesterot (-25%) and ApoB (-17%) decreased after ACTH, but not after betamethasone administration. Also, the elevation of plasma ApoB-48 in response to fat intake (to twice the basal levels) was markedly reduced after ACTH administration. However, the postprandial rise in plasma triglycerides and retinyl palmitate was unimpaired, suggesting that ACTH administration induced the secretion of fewer but larger chylomicrons. The effect of betamethasone on the postprandial response was similar but less pronounced. This study confirms earlier reports on the lipid-lowering effects of ACTH and supports our theory, based on in vitro studies, that the lipid-lowering effects of ACTH administration in man involves an inhibition of ApoB production. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults

BACKGROUND: Apolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, focused mainly on men, or with limited postprandial characterisation of participants. In the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we investigated the impact of APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids, glucose and insulin levels in healthy adults. FINDINGS: Healthy participants (n = 147) consumed a standard test breakfast (0 min; 49 g fat) and lunch (330 min; 29 g fat), with blood samples collected before (fasting) and on 11 subsequent occasions until 480 min after the test breakfast. The ins/ins homozygotes had higher fasting total cholesterol, LDL-cholesterol, TAG, insulin and HOMA-IR and lower HDL-cholesterol than del/del homozygotes (P < 0.017). A higher area under the time response curve (AUC) was evident for the postprandial TAG (P < 0.001) and insulin (P = 0.032) responses in the ins/ins homozygotes relative to the del/del homozygotes, where the genotype explained 35% and 7% of the variation in the TAG and insulin AUCs, respectively. CONCLUSIONS: In summary, our findings indicate that the APOB ins/del polymorphism is likely to be an important genetic determinant of the large inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake.

Use of water-miscible retinyl palmitate as markers of chylomicrons gives earlier peak response of plasma retinyl esters compared with oil-soluble retinyl palmitate

Delayed peak response of plasma retinyl esters (RE) relative to plasma triacylglycerols (TAG) and apolipoprotein (Apo) B-48 responses following a fat load supplemented with vitamin A raised doubts about the use of vitamin A to label dietary-derived lipids and lipoproteins. The present study compared the use of water-miscible and oil-soluble retinyl palmitate (RP) as markers of dietary-derived lipoproteins in healthy subjects along with the measurements of postprandial plasma TAG and ApoB-48 responses to investigate whether the delayed peak response observed was due to delayed intestinal output of RE from oil-based solutions. Nine healthy female subjects were given a standard test meal containing a dose (112 mg) of RP in either water-miscible or oil-soluble form in random order, on two separate occasions after a 12 h overnight fast. The results showed that the mean plasma RE concentrations reached a peak significantly later than mean plasma TAG and ApoB-48 concentrations when oil-soluble RP was consumed, whereas plasma RE peaked earlier relative to plasma TAG and ApoB-48 responses when water-miscible RP was used. The results suggested a more rapid absorption with a significantly higher and earlier peak response of plasma RE when water-miscible RP was consumed. This was in contrast to the delayed initial appearance and later sustained higher concentrations of plasma RE during the late postprandial period when oil-soluble RP was consumed. The RE response to the water-miscible RP showed better concordance with plasma TAG response than that of oil-soluble RP.

Lack of influence of test meal fatty acid composition on the contribution of intestinally-derived lipoproteins to postprandial lipaemia

The extent and duration of postprandial lipaemia have been linked to risk of CHD but the influence of dietary variables on, and the relative contributions of, exogenous (chylomicron) and endogenous (VLDL) triacylglycerols to the total lipaemic response have not been comprehensively evaluated. In the present study the triacylglycerol, apolipoprotein (apo) B-48 and retinyl ester (RE) responses to three test meals of varying monounsaturated (MUFA) and saturated fatty acid (SFA) content were measured in the triacylglycerol-rich lipoprotein (TRL) fraction of plasma (r ¼ 1·006 g/ml) for 9 h after meal consumption. Fifteen healthy normolipidaemic young men consumed, on separate occasions, three test meals which were identical apart from their MUFA and SFA contents. Expressed as a percentage of total energy the MUFA/SFA contents of the meals were: (1) 12 %/17 %; (2) 17 %/12% and (3) 24 %/5 %. The contribution of the intestinally-derived lipoproteins (chylomicrons) to the lipaemic response was investigated by determining the time to reach peak concentration and the total and incremental areas under the time response curves (AUC and incremental AUC) for RE, apoB-48 and triacylglycerol in the TRL fraction. No significant differences in these measurements were observed for the three meals. However, visual comparison of the postprandial responses to the three meals suggested that as meal MUFA content increased there was a tendency for the triacylglycerol, apoB-48 and RE responses to become biphasic as opposed to the typical monophasic response seen with the 12% MUFA/17% SFA meal. Comparison of the apoB-48 and RE responses for the three test meals confirmed other workers’ findings of delayed entry of RE relative to apoB-48 in TRL. The value of the two markers in investigating dietary fat absorption and metabolism is discussed.

PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.

A period 2 genetic variant interacts with plasma SFA to modify plasma lipid concentrations in adults with metabolic syndrome

Genetic variants of Period 2 (PER2), a circadian clock gene, have been linked to metabolic syndrome (MetS). However, it is still unknown whether these genetic variants interact with the various types of plasma fatty acids. This study investigated whether common single nucleotide polymorphisms (SNPs) in the PER2 locus (rs934945 and rs2304672) interact with various classes of plasma fatty acids to modulate plasma lipid metabolism in 381 participants with MetS in the European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL-TG), total cholesterol, apoC-II, apoB, and apoB-48 concentrations (P-interaction < 0.001–0.046). Carriers of the minor allele (GC+GG) with the highest SFA concentration (>median) had a higher plasma TG concentration (P = 0.001) and higher TRL-TG (P < 0.001) than the CC genotype. In addition, participants carrying the minor G allele for rs2304672 SNP and with a higher SFA concentration (>median) had higher plasma concentrations of apo C-II (P < 0.001), apo C-III (P = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may influence lipid metabolism by interacting with the plasma total SFA concentration in participants with MetS. The understanding of these gene-nutrient interactions could help to provide a better knowledge of the pathogenesis in MetS.