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Biomedical subjects

H M Roche

Publications and source records attributed to H M Roche.

At least 19 recordsLinked to original sources
PubMed2005

Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach.

Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.

Animal Feed↗
PubMed2005

Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men.

INTRODUCTION: Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism in experimental animals and cells in culture, but there are limited human data available. OBJECTIVE: To investigate the effect of CLA supplementation on biomarkers of calcium and bone metabolism in healthy adult males. DESIGN: The study consisted of a double-blind, placebo-controlled trial in which 60 healthy adult males (aged 39-64 y) were randomly assigned to receive daily either 3.0 g CLA isomer blend (50:50% cis-9,trans-11:trans-10,cis-12 isomers) or a palm/bean oil blend (placebo) for 8 weeks. Urine and blood samples were collected at weeks 0 and 8 and were analysed for biomarkers of calcium and bone metabolism. RESULTS: Supplementation with CLA or placebo for 8 weeks had no significant effects on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline), or on serum or urinary calcium levels. Baseline levels of these biochemical parameters were similar in both groups of subjects. While the placebo had no effect, CLA supplementation resulted in a three-fold increase (P<0.00001) in cis-9,trans-11 CLA isomer in total plasma lipids. CONCLUSION: Under the conditions tested in this double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism. Further investigation of the effects of CLA on calcium and bone metabolism in other gender- and age-groups is warranted.

Adult↗
PubMed2005

The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers.

OBJECTIVE: To assess the effects of dietary supplementation using two isomeric blends of conjugated linoleic acid (CLA) on immune function in healthy human volunteers. DESIGN: Double-blind, randomised, placebo-controlled intervention trial. SUBJECTS AND INTERVENTION: A total of 55 healthy volunteers (n=20 males, n=35 females) were randomised into one of three study groups who received 3 g/day of a fatty acid blend containing a 50:50 cis-9, trans-11: trans-10, cis-12 CLA isomer blend (2 g CLA), and 80:20 cis-9, trans-11: trans-10, cis-12 (80:20) CLA isomer blend (1.76 g CLA) or linoleic acid (control, 2 g linoleic acid) for 8 weeks. RESULTS: Supplementation with the 80:20 CLA isomer blend significantly (P< or =0.05) enhanced PHA-induced lymphocyte proliferation. CLA decreased basal interleukin (IL)-2 secretion (P< or =0.01) and increased PHA-induced IL-2 and tumor necrosis factor alpha (TNF(alpha)) production (P< or =0.01). However, these effects were not solely attributable to CLA as similar results were observed with linoleic acid. CLA supplementation had no significant effect on peripheral blood mononuclear cells IL-4 production, or on serum-soluble intercellular adhesion molecule-1 (sICAM-1) or plasma prostaglandin E2 (PGE2) or leukotreine B4 (LTB4) concentrations. CONCLUSIONS: This study shows that CLA supplementation had a minimal effect on the markers of human immune function. Furthermore, supplementation with CLA had no immunological benefit compared with linoleic acid.

Adult↗
PubMed2004

Dietary lipids and gene expression.

Nutrition is a key environmental factor that is particularly involved in the pathogenesis and progression of several polygenic, diet-related diseases. Nutrigenomics refers to the interaction between nutrition and the human genome. Dietary fatty acids interact with multiple nutrient-sensitive transcription factors. This explains the molecular basis of some of the health effects associated with altered dietary fatty acid composition. The metabolic syndrome is a very common condition, characterized by insulin resistance, abdominal obesity, dyslipidaemia and hypertension. It often precedes Type 2 diabetes mellitus, and is associated with a greater risk of cardiovascular disease. Several lines of evidence suggest that the interaction between nutrient-derived metabolic stressors and pro-inflammatory signals play an important role in the aetiology of insulin resistance and the development of the metabolic syndrome. This paper will address the interaction between several nutrient-sensitive transcription factors, including SREBP (sterol-regulatory-element-binding protein) and NFkappaB (nuclear factor kappaB), demonstrating how this interaction may be altered with dietary fatty acid interventions.

Adipose Tissue↗
PubMed2004

Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism.

BACKGROUND: Regular intake of plant sterol (phytosterol)-enriched foods enhances the cholesterol lowering effect of diets. One side effect associated with plant sterol consumption is a modest reduction in plasma carotenoid concentrations. This study investigated the effect of consuming a low-fat National Cholesterol Education Programme (NCEP) Step 1 diet, including a low-fat plant sterol ester (PSE)-enriched spread on cholesterol metabolism to determine if specific dietary advice to increase daily fruit and vegetable intake could prevent reduced plasma carotenoid concentrations. MATERIALS AND METHODS: In this randomised, crossover double-blind trial, 48 hypercholesterolaemic men received 21 g day(-1) of a low-fat PSE-enriched spread or placebo for 3 weeks, interrupted by 3 weeks washout. Individuals also adhered to a NCEP Step 1 diet and repeated 3-day food diaries monitored adherence. Specific advice was provided to increase dietary fruit and vegetable intakes. Fasting blood samples were collected at pre- and post-intervention for lipoprotein and carotenoid analysis. RESULTS: Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly (P <0.05) reduced, by 4.6 and 7.1%, respectively, after the PSE-enriched low-fat spread. Plasma apo B concentrations were significantly (P <0.0005) lower after the PSE spread. PSE consumption was also associated with significantly (P <0.05) lower total plasma beta-carotene concentrations, but this change was not significant after lipid standardisation. PSE consumption had no effect on retinol, alpha-carotene, gamma-tocopherol, alpha-tocopherol, lutein, zeaxanthin, beta-crypyoxanthin or lycopene concentrations. CONCLUSION: Dietary advice to increase daily fruit and vegetable consumption may be effective in preventing a reduction in plasma carotenoid concentrations previously associated with PSE consumption. Further, PSE incorporated in a low-fat spread and consumed as part of a NCEP Step 1 diet are effective in reducing total and LDL cholesterol.

Adult↗
PubMed2003

Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study.

Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.

Age Factors↗
PubMed2001

Susceptibility of LDL to oxidative modification in healthy volunteers supplemented with low doses of n-3 polyunsaturated fatty acids.

The objective of the present study was to evaluate the oxidative susceptibility of LDL in human volunteers following supplementation with various low doses (<1 g/d) of n-3 polyunsaturated fatty acids (PUFA). Sixty-two healthy volunteers (thirty-seven males and twenty-five females, aged 19-63 years) were recruited to take part in a randomised placebo-controlled trial. Volunteers were required to take 0.9, 0.6 or 0.3 g n-3 PUFA as fish oil or placebo capsules daily for 16 weeks. Susceptibility of LDL to oxidative modification was assessed by measuring the production of conjugated dienes and thiobarbituric acid-reactive substances in LDL oxidised by Cu2+ (15 microM) or 2,2'-azobis(2-amidinopropane) dihydrochloride (1 mM) for 5 h. Plasma fatty acid and LDL-fatty acid composition, cholesterol levels and antioxidant concentrations were also measured. While post-treatment n-3 PUFA compositions of plasma and LDL reflected the capsule contents, no meaningful differences in antioxidant concentrations or cholesterol levels were observed between the groups. Supplementation with low doses of n-3 PUFA as fish oil did not influence the oxidative susceptibility of LDL. The results of the present study suggest that moderate dietary intakes of n-3 PUFA do not significantly influence the susceptibility of LDL to oxidative modification in vitro.

Adult↗
PubMed2001

Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells.

Conjugated linoleic acid (CLA) is a collective term referring to the positional and geometric isomers of linoleic acid. This novel fatty acid has been shown to have a number of beneficial actions, including immunomodulatory, anticarcinogenic, and antiatherogenic effects. Tight junctions of epithelial cells determine epithelial membrane integrity and selective paracellular permeability to ions and macromolecules. Occludin and ZO-1 are integral structural components of the tight junction, which are involved in the biogenesis and functional integrity of the epithelial monolayer. This study investigated the effects of two isomers of CLA (cis-9 and trans-10 isomers) on Caco-2 cell transepithelial resistance (TER) development, paracellular epithelial permeability, and occludin and ZO-1 expression. Caco-2 cells were grown in media supplemented with 0.05 mM linoleic acid, cis-9 CLA, or trans-10 CLA for 21 days. The trans-10 CLA isomer delayed Caco-2 cell TER development, which is an in vitro measure of epithelial cell integrity, and increased paracellular epithelial permeability. Immunofluorescent staining of Caco-2 cell epithelial monolayers grown in media supplemented trans-10 CLA showed that the trans-10 CLA isomer altered distribution of occludin and ZO-1. The trans-10 CLA isomer delayed the acquisition of transepithelial resistance and altered the cellular distribution of occludin, which have important implications in relation to epithelial permeability.

Analysis of Variance↗
PubMed2000

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans.

OBJECTIVE: To examine the effect of low-dose fish oil supplementation on specific growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. DESIGN: Randomized placebo-controlled double-blind intervention study. SETTING: Free-living population. SUBJECTS: Sixty-three healthy volunteers, 37 males and 26 females. INTERVENTIONS: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 g/day of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. RESULTS: Consumption of fish oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFbeta) concentration. Furthermore, fish oil supplementation did not alter the total growth factor activity of serum. CONCLUSIONS: Results indicate that low-dose fish oil supplementation, equivalent to about two portions of fatty fish per week and providing less than 1 g n-3 PUFA/day, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. SPONSORSHIP: European Union shared cost project (FAIR-CT-95-0085).

Adult↗
PubMed2000

Differences in glucose-dependent insulinotrophic polypeptide hormone and hepatic lipase in subjects of southern and northern Europe: implications for postprandial lipemia.

BACKGROUND: This study was an extension of a previous study that showed different lipemic responses to standard test meals in subjects from southern and northern Europe. OBJECTIVE: The aim was to determine in 32 healthy young men from northern and southern Europe whether differences in the secretion of insulin and glucose-dependent insulinotrophic polypeptide (GIP) might explain these findings through the actions of these hormones on lipoprotein lipase. DESIGN: We investigated in a randomized, single-blind, crossover study the effects of 2 test meals of identical macronutrient composition but different saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) contents on postprandial GIP, insulin, the ratio of incremental triacylglycerol to apolipoprotein B-48 (a marker of chylomicron size), and the activity of postheparin lipases. RESULTS: Fasting and postprandial GIP concentrations and postheparin hepatic lipase activities were significantly higher in the southern Europeans (P < 0.001 and P < 0.02, respectively). Lipoprotein lipase activity after the SFA-rich meal was significantly higher in the northern Europeans (P < 0.01). HL activity 9 h after the SFA-rich meal and the area under the curve (AUC) for the postprandial insulin response correlated with the AUC for the postprandial GIP response [r = 0.44 (P < 0.04) and r = 0.46 (P < 0.05), respectively]. There were no significant differences in chylomicron size between the 2 groups for either meal, but when the groups were combined there was a significant difference in chylomicron size between the SFA- and MUFA-rich meals (P < 0.05), which could be due to the formation of larger chylomicrons after the MUFA-rich meal. CONCLUSION: The significantly higher GIP and insulin responses and HL activities in southern Europeans may provide an explanation for our previous report of attenuated postprandial triacylglycerol and apolipoprotein B-48 responses in them.

Adult↗
PubMed2000

Effect of long-chain n-3 polyunsaturated fatty acids on fasting and postprandial triacylglycerol metabolism.

Elevated plasma triacylglycerol concentrations have been associated with increased risk of coronary heart disease (CHD). In the past, the epidemiologic evidence about the causal role of triacylglycerols in CHD has not been well regarded, but recent prospective evidence shows that nonfasting plasma triacylglycerol concentration is a strong and independent predictor of future myocardial infarction. Elevated plasma triacylglycerol concentrations are associated with other CHD risk factors, namely reduced HDL-cholesterol concentrations and a preponderance of highly atherogenic, small, dense LDL particles. Plasma triacylglycerol concentrations increase after the ingestion of a fat-containing meal, and elevated postprandial triacylglycerolemia leads to a series of metabolic reactions that reduce HDL-cholesterol concentrations and promote the formation of small, dense LDL particles. The magnitude of the postprandial response is largely determined by fasting plasma triacylglycerol concentrations. Metabolism of plasma triacylglycerols also influences postprandial factor VII activation and the postprandial lipemic responsiveness to dietary cholesterol. Therefore, dietary factors that improve fasting plasma triacylglycerol concentrations must have a role in a healthy diet. Eicosapentaenoic and docosahexaenoic acids are n-3 polyunsaturated fatty acids (PUFAs) in fish oil that effectively reduce plasma triacylglycerol concentrations. Because n-3 PUFAs are effective at low doses (1 g n-3 PUFA/d), they provide a realistic option for the optimization of plasma triacylglycerol metabolism.

Cholesterol, HDL↗
PubMed2000

The impact of postprandial lipemia in accelerating atherothrombosis.

Several clinical studies have shown that the magnitude and duration of postprandial lipemia is positively related to the pathogenesis and progression of coronary heart disease. Postprandial lipid metabolism refers to the series of metabolic events that occur following the ingestion of a meal containing fat. Dietary fat is principally composed of triacylglycerol, postprandial lipaemia therefore being characterized by an increase in plasma triacylglycerol concentration. This review will describe the nature of the postprandial response and show the direct and indirect pro-atherogenic effects of triacylglycerol-rich lipoprotein metabolism. An elevated postprandial lipemic response precipitates a number of adverse metabolic events, including the production of atherogenic chylomicron remnants, the formation of the highly atherogenic small, dense low-density lipoprotein particles, and a reduction in the concentration of the cardioprotective high-density lipoprotein fraction. Postprandial lipemia also interacts with the process of thrombosis, in that an elevated postprandial triacylglycerol-rich lipoprotein concentration has the ability to activate the coagulation factor VII and plasminogen activator inhibitor. In the light of the potential impact of an elevated postprandial lipemia on atherothrombosis, the genetic determinants of the magnitude of the postprandial response will be identified. Finally, the nutritional factors that modulate the postprandial response will also be discussed.

Coronary Artery Disease↗
PubMed2000

Postprandial factor VII metabolism: the effect of the R353Q and 10 bp polymorphisms.

Elevated levels of coagulation factor VII activity (FVIIc) are associated with increased risk of CHD. FVIIc is strongly determined by two polymorphisms (R353Q and 0/10 base pairs (bp)) and plasma triacylglycerol (TAG) concentrations. The Q and 10 bp polymorphisms show strong linkage disequilibrium and have been associated with lower levels of fasting FVII, but there has been little investigation of the effect of these genotypes on the postprandial FVII metabolism. The present study demonstrated that fasting activated factor VII (FVIIa) and factor VII antigen (FVIIag) levels were significantly lower in the heterozygotes carrying the Q and 10 bp alleles (n 12), than in the R/0 bp homozygotes (n 12) (43.0 (SE 4.8) v. 23.9 (SE 6.5) mU/ml and 85.7 (SE 5.4) v. 71.6 (SE 7.5)% respectively). During postprandial lipaemia there was a significant increase in FVIIa in R/0 bp homozygotes but not in the heterozygotes carrying the Q and 10 bp alleles. The proportion of FVIIa (FVIIa:FVIIag) increased in the homozygotes but not in the heterozygotes (2.04 (SE 0.35) v. 1.20 (SE 0.26) respectively). Therefore possession of the relatively common Q and 10 bp alleles is not associated with postprandial activation of FVII, which may in turn have a protective effect against CHD.

Adult↗
PubMed2000

Effect of postprandial lipaemia and Taq 1B polymorphism of the cholesteryl ester transfer protein (CETP) gene on CETP mass, activity, associated lipoproteins and plasma lipids.

A large number of studies in recent years have investigated the effects of hyperlipidaemias and diabetes on cholesteryl ester transfer protein (CETP) on neutral lipid transfer activity and plasma lipids. There has been an ongoing debate as to whether CETP is pro- or anti-atherogenic as it provides a mechanism for the transfer of cholesterol from the cardioprotective HDL subfraction to the potentially atherogenic LDL subfraction. This study was designed to investigate whether there was significant variability of CETP mass and activity in a large normolipidaemic population and whether there is an association between CETP and plasma lipoprotein composition. The presence of a known polymorphism of CETP gene (Taq 1B) was investigated to see if there was any association between this polymorphism and CETP mass and activity, and plasma lipids. There was significant (P < 0.0001) increase in CETP mass and activity in plasma postprandially at 6 h. Using multiple stepwise regression analysis there was significant association with fasting CETP mass and activity (beta = 0.055; P = 0.002) and triacylglycerol-rich lipoprotein (beta = 0.013; P = 0.005) and postprandial CETP mass (beta = 0.254; P = 0.007). Repeated-measures analysis showed a strong association between the absence of Taq 1B polymorphism and low CETP mass and elevated HDL- and HDL2-cholesterol and HDL-phospholipid concentrations than did those who were homozygous or heterozygous for the presence of the restriction site.

Adult↗
PubMed1999

Long-chain n-3 polyunsaturated fatty acids and triacylglycerol metabolism in the postprandial state.

Elevated plasma triacylglycerol (TG; triglyceride) concentrations, especially in the postprandial state, have been associated with an increased risk of coronary heart disease (CHD). Postprandial lipemia represents a complex series of reactions which occur following the ingestion of a meal containing fat and is associated with a number of adverse metabolic events including the production of atherogenic chylomicron remnants, the formation of the highly atherogenic small dense low density lipoprotein particles, a reduction in the concentration of the cardioprotective high density lipoprotein fraction and the activation of coagulation factor VII. Fish oils are a rich source of the long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid and docosahexaenoic acid. Long chain n-3 PUFA are effective hypotriglyceridemic agents, lowering both fasting and postprandial TG concentrations. There is a large body of evidence which shows that n-3 PUFA reduces plasma TG concentrations through reduced endogenous very low density lipoprotein production. This in turn may account for the reduced postprandial lipemic response following n-3 PUFA supplementation. However, this does not preclude a contribution of enhanced chylomicron clearance, which may be mediated through altered chylomicron size, structure or chemical composition, or altered lipoprotein lipase metabolism in terms of enzyme concentration, activity, or affinity for chylomicrons. However the precise biochemical nature of this effect remains to be established. The reduction of postprandial plasma TG concentrations by n-3 PUFA may partly explain why n-3 PUFA intake is inversely related to CHD mortality.

Cardiotonic Agents↗
PubMed1999

Unsaturated fatty acids.

There is good scientific evidence that dietary fatty acid composition is involved in the aetiology of many diseases. Increasing the supply of n-3 polyunsaturated fatty acids (PUFA) may reduce the risk of CHD. Several scientific organizations (for example, see Department of Health, 1991, 1994; British Nutrition Foundation, 1992; Scientific Committee for Food, 1993; Food and Agriculture Organization/World Health Organization, 1998) have made recommendations for n-3 PUFA; however, there is a high degree of variation both in terms of the type and amount of n-3 PUFA (up to 7-fold). This variation reflects the different scientific axioms which underlie the different recommendations. Optimal nutrition may be defined in terms of the level of a nutrient required to avoid deficiency, or the amount required to have an effect on biomarkers and functional indicators of nutrient intake, or the level of a nutrient which prevents disease. Functional biomarkers of n-3 PUFA include plasma, platelet and erythrocyte phospholipid-n-3 PUFA levels. Plasma triacylglycerol concentrations represent a functional indicator of n-3 PUFA because n-3 PUFA exert a consistent hypotriacylglycerolaemic effect which is dose-dependent and persistent. In terms of disease status, epidemiological studies have demonstrated that the incidence of CHD is inversely associated with consumption of n-3 PUFA. Despite the health benefits of n-3 PUFA, the mean daily intake falls far short of most of the recommendations. Increasing fish intake is the most obvious way to increase n-3 PUFA intake. However, a large percentage (up to 65) of the population do not eat fish. Thus, there is a need for alternative sources of n-3 PUFA, such as functional foods, whose unique fatty acid composition could fortify staple foods thereby promoting optimal levels of n-3 PUFA intake.

Coronary Disease↗
PubMed1999

Dietary carbohydrates and triacylglycerol metabolism.

There is a growing body of scientific evidence which demonstrates that plasma triacylglycerol (TAG) concentration, especially in the postprandial state, is an important risk factor in relation to the development of CHD. Postprandial hypertriacylglycerolaemia is associated with a number of adverse metabolic risk factors, including the preponderance of small dense LDL, low HDL-cholesterol concentrations and elevated factor VII activity. Traditionally, a low-fat high-carbohydrate diet was used to prevent CHD because it effectively reduces plasma cholesterol concentrations, but this dietary regimen increases plasma TAG concentrations and reduces HDL-cholesterol concentrations. There is substantial epidemiological evidence which demonstrates that high plasma TAG and low plasma HDL concentrations are associated with an increased risk of CHD. Thus, there is reason for concern that the adverse effects of low-fat high-carbohydrate diets on TAG and HDL may counteract or negate the beneficial effect of reducing LDL-cholesterol concentrations. Although there have been no prospective studies to investigate whether reduced fat intake has an adverse effect on CHD, there is strong epidemiological evidence that reducing total fat intake is not protective against CHD. On the other hand, high-fat diets predispose to obesity, and central obesity adversely affects TAG metabolism. There is substantial evidence that in free-living situations low-fat high-carbohydrate diets lead to weight loss, which in turn will correct insulin resistance and plasma TAG metabolism. Clearly there is a need for prospective studies to resolve the issue as to whether low-fat high-carbohydrate diets play an adverse or beneficial role in relation to the development of CHD.

Coronary Disease↗