Effects of dietary fatty acid composition on basal and hormonestimulated hepatic lipogenesis and on circulating lipids in the rat

Thirty male rats were randomly assigned to one of three dietary groups in which the source of dietary fat was either a mixed oil, maize oil or fish oil. Effects of dietary fatty acid composition on in virro rates of [U-'4C]glucose incorporation into hepatic total lipids and into hepatic triacylglycerol were measured under basal, insulin (4 nM)-, gastric inhibitory polypeptide (GIP; 6 mi)- and insulin + GIP (4 nM + 6 n ~ ) - stimulated conditions. Effects of the three diets on postprandial plasma triacylglycerol, cholesterol, insulin and GIP concentrations were also measured. The fish-oil diet decreased rates of basal glucose incorporation into hepatic total lipids (P < 0.05) and hepatic triacylglycerol (P < 0.01) compared with the mixed-oil diet. The presence of insulin + GIP in the incubation medium stimulated glucose incorporation into hepatic total lipids in the maize-oil (P < 0.01) and fish-oil groups (P < OW), as well as into hepatic triacylglycerol in the maize-oil group (P < 0.005). In addition, the fish-oil diet decreased postprandial plasma triacylglycerol levels compared with both other dietary groups (P < 0-05 both cases), and the mixed-oil diet markedly increased postprandial plasma insulin levels compared with the other dietary groups (P c 0.001).

Incorporation of cis-9,trans-11 or trans-10,cis-12 conjugated linoleic acid into plasma and cellular lipids in healthy men

This study investigated the incorporation of cis-9,trans-11 conjugated linoleic acid (c9,t11 CLA) and trans-10,cis-12-CLA (t10,c12 CLA) into plasma and peripheral blood mononuclear cell (PBMC) lipids when consumed as supplements highly enriched in these isomers. Healthy men (n = 49, age 31 +/- 8 years) consumed one, two, and four capsules containing similar to600 mg of either c9,t11 CIA or t10,c12 CLA per capsule for sequential 8 week periods followed by a 6 week washout before consuming the alternative isomer. Both isomers were incorporated in a dosedependent manner into plasma phosphatidylcholine (PC) (c9,t11 CLA r = 0.779, t10,c12 CLA r = 0.738; P < 0.0001) and cholesteryl ester (CE) (c9,t11 CLA r = 0.706, t10,c12 CLA r = 0.788; P < 0.0001). Only t10,c12 CLA was enriched in plasma nonesterified fatty acids. Both c9,t11 CIA and t10,c12 CLA were incorporated linearly into PBMC total lipids (r = 0.285 and r = 0.273, respectively; P < 0.0005). The highest concentrations of c9,t11 CLA and t10,c12 CLA in PBMC lipids were 3- to 4-fold lower than those in plasma PC and CE. These data suggest that the level of intake is a major determinant of plasma and PBMC CLA content, although PBMCs appear to incorporate both CLA isomers less readily.

Incorporation of cis-9, trans-11 conjugated linoleic acid and vaccenic acid (trans-11 18 : 1) into plasma and leucocyte lipids in healthy men consuming dairy products naturally enriched in these fatty acids

The present study investigated whether consuming dairy products naturally enriched in cis-9, trans-11 (c9,t11) conjugated linoleic acid (CLA) by modification of cattle feed increases the concentration of this isomer in plasma and cellular lipids in healthy men. The study had a double-blind cross-over design. Subjects aged 34-60 years consumed dairy products available from food retailers for 1 week and then either control (0.17 g c9,t11 CLA/d; 0.31 g trans-vaccenic acid (tVA)/d) or CLA-enriched (1.43 g c9,t11 CLA/d; 4.71 g tVA/d) dairy products for 6 weeks. After 7 weeks washout, this was repeated with the alternate products. c9,t11 CLA concentration in plasma lipids was lower after consuming the control products, which may reflect the two-fold greater c9,t11 CLA content of the commercial products. Consuming the CLA-enriched dairy products increased the c9,t11 CLA concentration in plasma phosphatidylcholine (PC) (38 %; P=0.035), triacylglycerol (TAG) (22 %; P < 0.0001) and cholesteryl esters (205 %; P < 0.0001), and in peripheral blood mononuclear cells (PBMC) (238 %; P < 0.0001), while tVA concentration was greater in plasma PC (65 %; P=0.035), TAG (98 %; P=0.001) and PBMC (84 %; P=0.004). Overall, the present study shows that consumption of naturally enriched dairy products in amounts similar to habitual intakes of these foods increased the c9,t11 CLA content of plasma and cellular lipids.

Animal nutrition and lipids in animal products and their contribution to human intake and health

Few EU countries meet targets for saturated fatty acid (SFA) intake. Dairy products usually represent the single largest source of SFA, yet evidence indicates that milk has cardioprotective properties. Options for replacing some of the SFA in milk fat with cis-monounsaturated fatty acids (MUFA) through alteration of the cow’s diet are examined. Also, few people achieve minimum recommended intakes (~450–500 mg/d) of the long chain n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Enrichment of EPA+DHA in poultry meat via bird nutrition is described and how this would impact on habitual intake is discussed.

Effects of schistosoma mansoni worms and eggs on circulating cholesterol and liver lipids in mice

It has previously been shown that experimental infections of the parasitic trematode Schistosoma mansoni, the adult worms of which reside in the blood stream of the mammalian host, significantly reduced atherogenesis in apolipoprotein E gene knockout (apoE(-/-)) mice. These effects occurred in tandem with a lowering of serum total cholesterol levels in both apoE(-/-) and random-bred laboratory mice and a beneficial increase in the proportion of HDL to LDL cholesterol. To better understand how the parasitic infections induce these effects we have here investigated the involvement of adult worms and their eggs on lipids in the host. Our results indicate that the serum cholesterol-lowering effect is mediated by factors released from S. mansoni eggs, while the presence of adult worms seemed to have had little or no effect. It was also observed that high levels of lipids, particularly triacylglycerols and cholesteryl esters, present in the uninfected livers of both random-bred and apoE(-/-) mice fed a high-fat diet were not present in livers of the schistosome-infected mice. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A continuum receptor model of hepatic lipoprotein metabolism

A mathematical model describing the uptake of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles by a single hepatocyte cell is formulated and solved. The model includes a description of the dynamic change in receptor density on the surface of the cell due to the binding and dissociation of the lipoprotein particles, the subsequent internalisation of bound particles, receptors and unbound receptors, the recycling of receptors to the cell surface, cholesterol dependent de novo receptor formation by the cell and the effect that particle uptake has on the cell's overall cholesterol content. The effect that blocking access to LDL receptors by VLDL, or internalisation of VLDL particles containing different amounts of apolipoprotein E (we will refer to these particles as VLDL-2 and VLDL-3) has on LDL uptake is explored. By comparison with experimental data we find that measures of cell cholesterol content are important in differentiating between the mechanisms by which VLDL is thought to inhibit LDL uptake. We extend our work to show that in the presence of both types of VLDL particle (VLDL-2 and VLDL-3), measuring relative LDL uptake does not allow differentiation between the results of blocking and internalisation of each VLDL particle to be made. Instead by considering the intracellular cholesterol content it is found that internalisation of VLDL-2 and VLDL-3 leads to the highest intracellular cholesterol concentration. A sensitivity analysis of the model reveals that binding, unbinding and internalisation rates, the fraction of receptors recycled and the rate at which the cholesterol dependent free receptors are created by the cell have important implications for the overall uptake dynamics of either VLDL or LDL particles and subsequent intracellular cholesterol concentration. (C) 2008 Elsevier Ltd. All rights reserved.

Pressure-jump X-ray studies of liquid crystal transitions in lipids

In this paper, we give an overview of our studies by static and time-resolved X-ray diffraction of inverse cubic phases and phase transitions in lipids. In 1, we briefly discuss the lyotropic phase behaviour of lipids, focusing attention on non-lamellar structures, and their geometric/topological relationship to fusion processes in lipid membranes. Possible pathways for transitions between different cubic phases are also outlined. In 2, we discuss the effects of hydrostatic pressure on lipid membranes and lipid phase transitions, and describe how the parameters required to predict the pressure dependence of lipid phase transition temperatures can be conveniently measured. We review some earlier results of inverse bicontinuous cubic phases from our laboratory, showing effects such as pressure-induced formation and swelling. In 3, we describe the technique of pressure-jump synchrotron X-ray diffraction. We present results that have been obtained from the lipid system 1:2 dilauroylphosphatidylcholine/lauric acid for cubic-inverse hexagonal, cubic-cubic and lamellar-cubic transitions. The rate of transition was found to increase with the amplitude of the pressure-jump and with increasing temperature. Evidence for intermediate structures occurring transiently during the transitions was also obtained. In 4, we describe an IDL-based 'AXCESS' software package being developed in our laboratory to permit batch processing and analysis of the large X-ray datasets produced by pressure-jump synchrotron experiments. In 5, we present some recent results on the fluid lamellar-Pn3m cubic phase transition of the single-chain lipid 1-monoelaidin, which we have studied both by pressure-jump and temperature-jump X-ray diffraction. Finally, in 6, we give a few indicators of future directions of this research. We anticipate that the most useful technical advance will be the development of pressure-jump apparatus on the microsecond time-scale, which will involve the use of a stack of piezoelectric pressure actuators. The pressure-jump technique is not restricted to lipid phase transitions, but can be used to study a wide range of soft matter transitions, ranging from protein unfolding and DNA unwinding and transitions, to phase transitions in thermotropic liquid crystals, surfactants and block copolymers.

Lipids and the immune response: from molecular mechanisms to clinical applications

Purpose of review This review critically evaluates recent studies investigating the effects of fatty acids on immune and inflammatory responses in both healthy individuals and in patients with inflammatory diseases, with some reference to animal studies where relevant. It examines recent findings describing the cellular and molecular basis for the modulation of immune function by fatty acids. The newly emerging area of diet-genotype interactions will also be discussed, with specific reference to the anti-inflammatory effects of fish oil. Recent findings Fatty acids are participants in many intracellular signalling pathways. They act as ligands for nuclear receptors regulating a host of cell responses, they influence the stability of lipid rafts, and modulate eicosanoid metabolism in cells of the immune system. Recent findings suggest that some or all of these mechanisms may be involved in the modulation of immune function by fatty acids. Summary Human studies investigating the relationship between dietary fatty acids and some aspects of the immune response have been disappointingly inconsistent. This review presents the argument that most studies have not been adequately powered to take into account the influence of variation (genotypic or otherwise) on parameters of immune function. There is well-documented evidence that fatty acids modulate T lymphocyte activation, and recent findings describe a range of potential cellular and molecular mechanisms. However, there are still many questions remaining, particularly with respect to the roles of nuclear receptors, for which fatty acids act as ligands, and the modulation of eicosanoid synthesis, for which fatty acids act as precursors.

Conjugated linoleic acid and human health: a critical evaluation of the evidence

Purpose of review: This review critically evaluates studies investigating the effects of conjugated linoleic acid on human health, including effects on body composition, blood lipids, liver metabolism, insulin sensitivity and immune function. It focuses mainly on human intervention studies, but includes some reference to animal and cellular studies which provide insight into potential molecular mechanisms of action of conjugated linoleic acid. Recent findings: Human studies continue to report inconsistent effects of conjugated linoleic acid on human health. Some of these reports are based on overinterpretation of marginal effects of supplementation. Recent data suggest that the effects of the substance may be isomer dependent and that cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acids have opposing effects on blood lipids and on metabolism in adipocytes and hepatic cells. Summary: Claims that conjugated linoleic acid is beneficial for health remain as yet unconvincing. Human studies investigating the effects of conjugated linoleic acid supplements have tended to use mixtures of isomers and have been inconsistent. More recent studies have attempted to use relatively pure preparations of single isomers and these studies suggest that the effects of conjugated linoleic acid may be isomer-specific. These recent data suggest a relative detrimental effect of trans-10, cis-12 conjugated linoleic acid on blood lipids. There appears to be little effect of conjugated linoleic acid on immune function and the effects on insulin sensitivity remain unclear.

Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans

Background: Conjugated linoleic acid (CLA) is reported to have weight-reducing and antiatherogenic properties when fed to laboratory animals. However, the effects of CLA on human health and, in particular, the effects of individual CLA isomers are unclear. Objective: This study investigated the effects of 3 doses of highly enriched cis-9,trans-11 (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 (0.63, 1.26, and 2.52 g/d) CLA preparations on body composition, blood lipid profile, and markers of insulin resistance in healthy men. Design: Healthy men consumed 1, 2, and 4 capsules sequentially, containing either 80% cis-9,trans-11 CLA or 80% trans-10,cis-12 CLA for consecutive 8-wk periods. This phase was followed by a 6-wk washout and a crossover to the other isomer. Results: Body composition was not significantly affected by either isomer of CLA. Mean plasma triacylglycerol concentration was higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA, although there was no influence of dose. There were significant effects of both isomer and dose on plasma total cholesterol and LDL-cholesterol concentrations but not on HDL-cholesterol concentration. The ratios of LDL to HDL cholesterol and of total to HDL cholesterol were higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA. CLA supplementation had no significant effect on plasma insulin concentration, homeostasis model for insulin resistance, or revised quantitative insulin sensitivity check index. Conclusion: Divergent effects of cis-9,trans-11 CLA and trans10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.

Effects of consumption of probiotics and prebiotics on serum lipid levels in humans

The objective of this article is to review existing studies concerning the effects of probiotics and prebiotics on serum cholesterol concentrations, with particular attention on the possible mechanisms of their action. Although not without exception, results from animal and human studies suggest a moderate cholesterol-lowering action of dairy products fermented with appropriate strain(s) of lactic acid bacteria and bifidobacteria. Mechanistically, probiotic bacteria ferment food-derived indigestible carbohydrates to produce short-chain fatty acids in the gut, which can then cause a decrease in the systemic levels of blood lipids by inhibiting hepatic cholesterol synthesis and/or redistributing cholesterol from plasma to the liver. Furthermore, some bacteria may interfere with cholesterol absorption from the gut by deconjugating bile salts and therefore affecting the metabolism of cholesterol, or by directly assimilating cholesterol. For prebiotic substances, the majority of studies have been done with the fructooligosaccharides inulin and oligofructose, and although convincing lipid-lowering effects have been observed in animals, high dose levels had to be used. Reports in humans are few in number. In studies conducted in normal-lipidemic subjects, two reported no effect of inulin or oligofructose on serum lipids, whereas two others reported a significant reduction in serum triglycerides (19 and 27%, respectively) with more modest changes in serum total and LDL cholesterol. At present, data suggest that in hyperlipidemic subjects, any effects that do occur result primarily in reductions in cholesterol, whereas in normal lipidemic subjects, effects on serum triglycerides are the dominant feature.

Effects of endogenous flour lipids on the quality of semisweet biscuits

Fractionation and reconstitution techniques were used to study the contribution of enclogenous flour lipids to the quality of semisweet (Rich Tea-type) biscuits. Biscuit flour was defatted with chloroform and baked with bakery fat but without enclogenous lipid addition. Semisweet biscuits baked from defatted flour were flatter, denser, and harder and showed collapse of gas cells during baking when compared with control biscuits. Defatted flour semisweet doughs exhibited a different rheological behavior from the control samples showing higher storage and loss moduli (G' and G" values), that is, high viscoelasticity. Functionality was restored when total nonstarch flour lipids were added back to defatted flour. Both the polar and nonpolar lipid fractions had positive effects in restoring flour quality, but the polar lipid fraction was of greatest benefit. Both fractions were needed for complete restoration of both biscuit quality and dough rheological characteristics.

Effects of endogenous flour lipids on the quality of short-dough biscuits

Fractionation and reconstitution techniques were used to study the contribution of endogenous flour lipids to the quality of short-dough (shortcake type) biscuits. Biscuit flour was defatted with chloroform and baked with bakery fat, but without endogenous lipid. Short-dough biscuits baked from defatted flour had smaller diameters, and were flatter, denser and harder than control biscuits. Defatted flour shortcake doughs exhibited different rheological behaviour from the control samples, showing higher storage and loss moduli (G' and G" values), ie higher viscoelasticity. Functionality was restored when total non-starch flour lipids were added back to defatted flour. The polar lipid fraction had a positive effect in restoring flour quality whereas the non-polar lipid fraction had no effect. Both fractions were needed for complete restoration of both biscuit quality and dough rheological characteristics. A study of the microstructure of defatted biscuits revealed that their gluten protein was more hydrated and developed than the gluten of the control biscuits. This conclusion was supported by the higher water absorption of the defatted gluten. (C) 2004 Society of Chemical Industry.