Saturated fat-induced changes in S-f 60-400 particle composition reduces uptake of LDL by HepG2 cells

The ability of human postprandial triacylglycerol-rich lipoproteins (TRLs), isolated after meals enriched in saturated fatty acids (SFAs), n-6 PUFAs, and MUFAs, to inhibit the uptake of I-125-labeled LDL by the LDL receptor was investigated in HepG2 cells. Addition of TRLs resulted in a dose-dependent inhibition of heparin-releasable binding, cell-associated radioactivity, and degradation products of I-125-labeled LDL (P < 0.001). SFA-rich Svedberg flotation rate (S-f) 60-400 resulted in significantly greater inhibition of cell-associated radioactivity than PUFA-rich particles (P = 0.016) and total uptake of I-125-labeled LDL compared with PUFA- and MUFA-rich particles (P = 0.02). Normalization of the apolipoprotein (apo)E but not apoC-III content of the TRLs removed the effect of meal fatty acid composition, and addition of an anti-apoE antibody reversed the inhibitory effect of TRLs on the total uptake of I-125-labeled LDL. Real time RT-PCR showed that the SFA-rich Sf 60-400 increased the expression of genes involved in hepatic lipid synthesis (P < 0.05) and decreased the expression of the LDL receptor-related protein 1 compared with MUFAs (P = 0.008). In conclusion, these findings suggest an alternative or additional mechanism whereby acute fat ingestion can influence LDL clearance via competitive apoE-dependent effects of TRL on the LDL receptor.-Jackson, K. G., V. Maitin, D. S. Leake, P. Yaqoob, and C. M. Williams. Saturated fat-induced changes in Sf 60 400 particle composition reduces uptake of LDL by HepG2 cells.

Performance of palm- based fat blends with a low saturated fat content in puff pastry

Four fat blends based on palm fractions in combination with high oleic sunflower oil (HOSF) with a relatively low saturated fatty acid content (29.2±0.85%, i.e. less than 50% of that of butter) were prepared. The saturated fat was located in different triacylglycerols (TAG) structures in each blend. Principal saturated TAG were derived from palm stearin (POs, containing tripalmitoyl glycerol - PPP), palm mid fraction (PMF, containing 1,3-dipalmitoyl-2-oleoyl glycerol - POP) and interesterified PMF (inPMF, containing PPP, POP and rac-1,2-dipalmitoyl-3-oleoyl glycerol - PPO). Thus, in blend 1, composed of POs and HOSF, the saturates resided principally in PPP. In blend 2, composed of POs, PMF and HOSF, the principal saturate-containing TAG were PPP and POP. Blend 3, composed of inPMF and HOSF, was similar to blend 2 except that the disaturated TAG comprised a 2:1 mixture of PPO:POP. Finally, blend 4, a mixture of PMF and HOSF, had saturates present mainly as POP. The physical properties and the functionality of blends, as shortenings for puff pastry laminated in a warm bakery environment (20-30°C), were compared with each other, and with butter. Puff pastry prepared with blend 1 (POs:HOSF 29:71) and blend 4 (PMF:HOSF 41:59), was very hard; blend 2 (POs:PMF:HOSF 13:19:68) was most similar to butter in the compressibility of the baked product and it performed well in an independent baking trial; blend 3 (inPMF:HOSF 40:60) gave a product that required a higher force for compression than butter.

Genetic predisposition to type 2 diabetes is associated with impaired insulin secretion but does not modify insulin resistance or secretion in response to an intervention to lower dietary saturated fat

Genome-wide association studies have identified SNPs reproducibly associated with type 2 diabetes (T2D). We examined the effect of genetic predisposition to T2D on insulin sensitivity and secretion using detailed phenotyping in overweight individuals with no diagnosis of T2D. Furthermore, we investigated whether this genetic predisposition modifies the responses in beta-cell function and insulin sensitivity to a 24-week dietary intervention. We genotyped 25 T2D-associated SNPs in 377 white participants from the RISCK study. Participants underwent an IVGTT prior to and following a dietary intervention that aimed to lower saturated fat intake by replacement with monounsaturated fat or carbohydrate. We composed a genetic predisposition score (T2D-GPS) by summing the T2D risk-increasing alleles of the 25 SNPs and tested for association with insulin secretion and sensitivity at baseline, and with the change in response to the dietary intervention. At baseline, a higher T2D-GPS was associated with lower acute insulin secretion (AIRg 4% lower/risk allele, P = 0.006) and lower insulin secretion for a given level of insulin sensitivity, assessed by the disposition index (DI 5% lower/risk allele, P = 0.002), but not with insulin sensitivity (Si). T2D-GPS did not modify changes in insulin secretion, insulin sensitivity or the disposition index in response to the dietary interventions to lower saturated fat. Participants genetically predisposed to T2D have an impaired ability to compensate for peripheral insulin resistance with insulin secretion at baseline, but this does not modify the response to a reduction in dietary saturated fat through iso-energetic replacement with carbohydrate or monounsaturated fat.

Development of a food-exchange model to replace saturated fat with MUFAS and n-6 PUFAS in adults at moderate cardiovascular risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFA, MUFA, and n-6 PUFA between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFA, MUFA, and n-6 PUFA for each diet group, with significant overall diet effects for total SFA and MUFA between groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFA with MUFA or n-6 PUFA with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

Low-fat food consumption by people with diabetes decreases fat saturated fat, and cholesterol intake

This study investigated the effect of providing free-access to several fat-modified foods on dietary energy and fat intake in free-living individuals with and without diabetes mellitus. Five low/no-fat products or their regular-fat versions were provided to volunteers to take home and use for 3 days. Energy and nutrient intakes of all foods consumed were determined through a weighed food diary and by weighing the food provided before and after consumption. Fifteen individuals with diabetes and 15 case-matched controls without diabetes participated in the study. Individuals with diabetes and controls responded similarly to the fat-modified foods. In both groups there was a significant reduction in the percent of kcals and grams of fat consumed during the low-fat condition compared to the regular-fat condition (p

Isoenergetic replacement of dietary saturated with monounsaturated fat via macadamia nuts enhances endothelial function in overweight subjects

Background & aims: - Excess adiposity (overweight) is one of numerous risk factors for cardiometabolic disease. Most risk reduction strategies for overweight rely on weight loss through dietary energy restriction. However, since the evidence base for long-term successful weight loss interventions is scant, it is important to identify strategies for risk reduction independent of weight loss. The aim of this study was to compare the effects of isoenergetic substitution of dietary saturated fat (SFA) with monounsaturated fat (MUFA) via macadamia nuts on coronary risk compared to usual diet in overweight adults. Methods: - A randomised controlled trial design, maintaining usual energy intake, but manipulating dietary lipid profile in a group of 64 (54 female, 10 male) overweight (BMI > 25), otherwise healthy, subjects. For the intervention group, energy intakes of usual (baseline) diets were calculated from multiple 3 day diet diaries, and SFA was replaced with MUFA (target: 50%E from fat as MUFA) by altering dietary SFA sources and adding macadamia nuts to the diet. Both control and intervention groups received advice on national guidelines for physical activity and adhered to the same protocol for diet diary record keeping and trial consultations. Anthropometric and clinical measures were taken at baseline and at 10 weeks. Results: A significant increase in brachial artery flow-mediated dilation (p < 0.05) was seen in the monounsaturated diet group at week 10 compared to baseline. This corresponded to significant decreases in waist circumference, total cholesterol (p < 0.05), plasma leptin and ICAM-1 (p < 0.01). Conclusions: - In patient subgroups where adherence to dietary energy-reduction is poor, isoenergetic interventions may improve endothelial function and other coronary risk factors without changes in body weight. This trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12607000106437).

Saturated and Trans Fatty Acids and Coronary Heart Disease

Dietary intake of both saturated and trans fatty acids has been associated with an increase in the risk of coronary heart disease (CHD). Evidence comes mainly from controlled dietary experiments with intermediate end points, such as blood lipoproteins, and from observational studies. A few small, randomized controlled trials with clinical end points have been carried out in which saturated fat was replaced with polyunsaturated fat, leading to a reduction in low-density lipoprotein cholesterol and a reduction in CHD risk. However, no such studies exist for trans fatty acids. More high-quality, randomized controlled trials on fatty acids and CHD are required, but public health recommendations to reduce intake of both saturated and trans fatty acids are appropriate based on the current evidence.

Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995–1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27–2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84–1.64) p for trend 5 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37–2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91–1.78) p for trend 5 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5–<25 kg/m2) [HR (95% CI) 0.76 (0.63–0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96–1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90–1.05)]. p for interaction 5 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.

Dietary fat and meat intakes and risk of reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma

The aim of our study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data were collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (ORs) and 95% confidence intervals (95% CIs), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR = 3.54; 95% CI = 1.32-9.46) and EAC (OR = 5.44; 95% CI = 2.08-14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR = 2.79; 95% CI = 1.11-7.04; OR = 2.41; 95% CI = 1.14-5.08, respectively) and monounsaturated fat intake (OR = 2.63; 95% CI = 1.01-6.86; OR = 5.35; 95% CI = 2.14-13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR = 3.15; 95% CI = 1.38-7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR = 4.67; 95% CI = 1.71-12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies investigating the association between dietary fat and food sources of fat are needed to confirm these results.

Dietary fat and breast cancer mortality: a systematic review and meta-analysis

Background: The influence of dietary fat upon breast cancer mortality remains largely understudied despite extensive investigation into its influence upon breast cancer risk 

Objective: To conduct meta-analyses of studies to clarify the association between dietary fat and breast cancer mortality Design: MEDLINE and EMBASE were searched for relevant articles published up to March 2012. Risk of all-cause or breast cancer specific death was evaluated by combining multivariable adjusted estimates comparing highest versus lowest categories of intake; and per 20 gram increase in intake of total and/or saturated fat (g/day) using random-effects meta-analyses. 

Results: Fifteen prospective cohort studies investigating total fat and/or saturated fat intake (g/day) and breast cancer mortality were included. There was no difference in risk of breast cancer specific death (n = 6; HR = 1.14; 95% CI: 0.86, 1.52; P = 0.34) or all cause death (n = 4; HR = 1.73; 95% CI: 0.82, 3.6; P = 0.15) for women in the highest versus lowest category of total fat intake. Breast cancer specific death (n = 5; HR = 1.63; 95% CI: 1.19, 2.24; p <0.01) was higher for women in the highest versus lowest category of saturated fat intake. 

Conclusions: These meta-analyses have shown that saturated fat intake negatively impacts upon breast cancer survival.

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

Cardiovascular risk is determined by the complex interactions between genetic and environmental factors. The apoE genotype represents the most-widely-studied single nucleotide polymorphism in relation to CVD risk, with >3600 publications cited in PubMed. Although originally described as a mediator of lipoprotein metabolism, the lipoprotein-independent functions of apoE are being increasingly recognised, with limited data available on the potential impact of genotype on these metabolic processes. Furthermore, although meta-analyses suggest that apoE4 carriers may have a 40-50% increased CVD risk, the associations reported in individual studies are highly heterogeneous and it is recognised that environmental factors such as smoking status and dietary fat composition influence genotype-phenotype associations. However, information is often derived from observational studies or small intervention trials in which retrospective genotyping of the cohort results in small group sizes in the rarer E2 and E4 subgroups. Either larger well-standardised intervention trials or smaller trials with prospective recruitment according to apoE genotype are needed to fully establish the impact of diet on genotype-CVD associations and to establish the potential of dietary strategies such as reduced total fat, saturated fat, or increased antioxidant intakes to counteract the increased CVD burden in apoE4 carriers.

Dietary fat composition and cardiovascular disease

Cardiovascular disease (CVD), which includes coronary heart disease and stroke, remains the major killer in the EU, being responsible for 42% of total mortality. The amount and composition of dietary fat is arguably the most important dietary factor contributing to disease risk. A significant body of consistent evidence indicates that a decrease in dietary saturated fat:unsaturated (polyunsaturated + monounsaturated) ratio and an increased intake of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) found in fish, is cardioprotective. Furthermore, although the evidence is currently less convincing, such a strategy is also likely to improve insulin sensitivity, the central metabolic defect in diabetes. Currently in the UK only 12% of men, 17% of women and 8% of children have an SFA intakes <10% of energy. The average intake of LC n-3 PUFA is <0.2 g/day, which is less than half the current conservative recommendation of a minimum of 0.45 g/day. Public health strategies to reverse these dietary fatty acid imbalances, aimed at educating and motivating the consumer and making affordable and acceptable food products with an ‘enhanced’ fatty acid profile more widely available, must remain a public health priority in the ‘fight’ against CVD.

Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome

Objective: In the metabolic syndrome (MetS), increased fat storage in ‘nonadipose’ tissues such as skeletal muscle may be related to insulin resistance (‘lipid overflow’ hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). Subjects and Methods: In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn−3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-13C]-palmitate to label chylomicron-TAG. Results: Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn−3 group compared to the HSFA group (ΔiAUC −139±67 vs 167±70 μmol l−1 min−1, P=0.009), together with decreased concentrations of [U-13C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. Conclusion: Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn−3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.