Plasma lipids and prolactin in patients with breast cancer

In a comparative study of pre- and postmenopausal women with benign and malignant breast disease, a number of differences were observed in circulating plasma prolactin and lipid concentrations. Plasma lipids, phospholipids, triglycerides, cholesterol and free fatty acids were all higher in blood obtained from breast cancer patients prior to surgery. HDL-Cholesterol levels were significantly lower in these patients. These differences remained when the patient groups were sub-divided according to menopausal status. Plasma prolactin concentrations were also found to be higher in cancer compared with non-cancer patients, this effect being more marked in premenopausal than in postmenopausal patients. Premenopausal patients with invasive or poorly differentiated disease had significantly higher prolactin levels than those with non-invasive disease. No correlations were found between plasma prolactin and any of the lipid fractions.

Variation in the FFAR1 gene modifies BMI, body composition and plasma lipids but not plasma insulin or Beta-cell function in overweight subjects

Background FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids. Methodology/Principal Findings For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m2 higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P<0.05) cholesterol, but also with lower HDL-cholesterol (0.09 mmol/L, P<0.05) although the difference was not apparent when controlling for multiple testing. There were no statistically significant effects of the three SNPs on insulin sensitivity or beta cell function. However accumulated risk allele showed a lower beta cell function on increasing plasma fatty acids with a carbon chain greater than six. Conclusions/Significance Differences in body composition and lipids associated with common SNPs in the FFAR1 gene were apparently not mediated by changes in insulin sensitivity or beta-cell function.

Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids

Objective: SNPs identified from genome wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods: Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total(P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

A highly oriented cubic phase formed by lipids under shear

We demonstrate the formation of a macroscopically oriented inverse bicontinuous cubic (QII) lipid phase from a sponge (L3) phase by controlled hydration during shear flow. The L3 phase was the monoolein/ butanediol/water system; the addition of water reduces the butanediol concentration, inducing the formation of a diamond (QIID) cubic phase, which is oriented by the shear flow. The phenomenon was reproduced in both capillary and Couette geometries, indicating that this represents a robust general route for the production of highly aligned bulkQII samples, with applications in nanomaterial templating and protein research.

Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk

The PPARγ2 gene SNP Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. We investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 White subjects aged 30-70 y at increased cardiometabolic risk, in the RISCK study. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet and after 24-week reference (HS), high-MUFA (HM) and low-fat (LF) diets. At recruitment, there were no significant associations between genotype and plasma lipids, however, P:S x genotype interaction influenced plasma total cholesterol (TC) (P=0.02), LDL-cholesterol (LDL-C) (P=0.002) and triglyceride (TG) (P=0.02) concentrations. At P:S ratio ≤0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in non-carriers (respectively P=0.003; P=0.0001). Significant trends in reduction of plasma TC (P=0.02) and TG (P=0.002) concentrations occurred with increasing P:S (respectively ≤0.33 to >0.65 and 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and non-carriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but are not dependent on a reduction in SFA intake.

Role of lipids in human nutrition

Fat is a major contributor to energy intake in most Western diets, supplying 35–40% of food energy. It is described as being ‘energy-dense’, because a gram of fat (9 kcal/g) yields more than twice as much metabolisable energy as a gram of either carbohydrate or protein (4 kcal/g). Most of the fat we consume in our diet is in the form of triacylglycerol (90-95%), with cholesterol and phospholipids making up the bulk of the remainder. Dietary advice invariably stresses the importance of fat reduction, yet fats have diverse roles in human nutrition. They are important as a source of energy, both for immediate utilisation by the body and in laying down a storage depot (adipose tissue) for later utilisation when food intake is reduced, they act as a vehicle for the ingestion and absorption of fat-soluble vitamins, and they have diverse structural and functional roles in the body. Cholesterol is also an essential component of cell membranes and is the precursor for synthesis of hormones. This chapter describes the structure, digestion, transport and functional properties of dietary fat in the body and explains the basis of associations between fat consumption and chronic disease.

Effect of forage conservation method on plasma lipids, mammary lipogenesis, and milk fatty acid composition in lactating cows fed diets containing a 60:40 forage-to-concentrate ratio

The effects of forage conservation method on plasma lipids, mammary lipogenesis, and milk fat were examined in 2 complementary experiments. Treatments comprised fresh grass, hay, or untreated (UTS) or formic acid treated silage (FAS) prepared from the same grass sward. Preparation of conserved forages coincided with the collection of samples from cows fed fresh grass. In the first experiment, 5 multiparous Finnish Ayrshire cows (229 d in milk) were used to compare a diet based on fresh grass followed by hay during 2 consecutive 14-d periods, separated by a 5-d transition during which extensively wilted grass was fed. In the second experiment, 5 multiparous Finnish Ayrshire cows (53 d in milk) were assigned to 1 of 2 blocks and allocated treatments according to a replicated 3 × 3 Latin square design, with 14-d periods to compare hay, UTS, and FAS. Cows received 7 or 9 kg/d of the same concentrate in experiments 1 and 2, respectively. Arterial concentrations of triacylglycerol (TAG) and phospholipid were higher in cows fed fresh grass, UTS, and FAS compared with hay. Nonesterified fatty acid (NEFA) concentrations and the relative abundance of 18:2n-6 and 18:3n-3 in TAG of arterial blood were also higher in cows fed fresh grass than conserved forages. On all diets, TAG was the principle source of fatty acids (FA) for milk fat synthesis, whereas mammary extraction of NEFA was negligible, except during zero-grazing, which was associated with a lower, albeit positive calculated energy balance. Mammary FA uptake was higher and the synthesis of 16:0 lower in cows fed fresh grass than hay. Conservation of grass by drying or ensiling had no influence on mammary extraction of TAG and NEFA, despite an increase in milk fat secretion for silages compared with hay and for FAS than UTS. Relative to hay, milk fat from fresh grass contained lower 12:0, 14:0, and 16:0 and higher S3,R7,R11,15-tetramethyl-16:0, cis-9 18:1, trans-11 18:1, cis-9,trans-11 18:2, 18:2n-6, and 18:3n-3 concentrations. Even though conserved forages altered mammary lipogenesis, differences in milk FA composition were relatively minor, other than a higher enrichment of S3,R7,R11,15-tetramethyl-16:0 in milk from silages compared with hay. In conclusion, differences in milk fat composition on fresh grass relative to conserved forages were associated with a lower energy balance, increased uptake of preformed FA, and decreased synthesis of 16:0 de novo in the mammary glands, in the absence of alterations in stearoyl-coenzyme A desaturase activity.

Self-assembly of three bacterially-derived bioactive lipopeptides

The self-assembly in aqueous solution of three lipopeptides obtained from Bacillus subtilis has been investigated. The lipopeptides surfactin, plipastatin and mycosubtilin contain distinct cyclic peptide headgroups as well as differences in alkyl chain length, branching and chain length distribution. Cryogenic transmission electron microscopy and X-ray scattering reveal that surfactin and plipastatin aggregate into 2 nm-radius spherical micelles, whereas in complete contrast mycosubtilin self-assembles into extended nanotapes based on bilayer ordering of the lipopeptides. Circular dichroism and FTIR spectroscopy indicate the presence of turn structures in the cyclic peptide headgroup. The unexpected distinct mode of self-assembly of mycosubtilin compared to the other two lipopeptides is ascribed to differences in the surfactant packing parameter. This in turn is due to specific features of the conformation of the peptide headgroup and alkyl chain branching.

Influence of SNPs in nutrient-sensitive candidate genes and gene–diet interactions on blood lipids: the DiOGenes study

Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene–diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP–diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP–dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of − 0·26 mmol/l per A-allele/protein unit (95 % CI − 0·38, − 0·14, P= 0·000043). In conclusion, we investigated SNP–diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.

Bioactive films produced from self-assembling peptide amphiphiles as versatile substrates for tuning cell adhesion and tissue architecture in serum-free conditions

The development of versatile bioactive surfaces able to emulate in vivo conditions is of enormous importance to the future of cell and tissue therapy. Tuning cell behaviour on two-dimensional surfaces so that the cells perform as if they were in a natural three-dimensional tissue represents a significant challenge, but one that must be met if the early promise of cell and tissue therapy is to be fully realised. Due to the inherent complexities involved in the manufacture of biomimetic three-dimensional substrates, the scaling up of engineered tissue-based therapies may be simpler if based upon proven two-dimensional culture systems. In this work, we developed new coating materials composed of the self-assembling peptide amphiphiles (PAs) C16G3RGD (RGD) and C16G3RGDS (RGDS) shown to control cell adhesion and tissue architecture while avoiding the use of serum. When mixed with the C16ETTES diluent PA at 13 : 87 (mol mol-1) ratio at 1.25 times 10-3 M, the bioactive {PAs} were shown to support optimal adhesion, maximal proliferation, and prolonged viability of human corneal stromal fibroblasts ({hCSFs)}, while improving the cell phenotype. These {PAs} also provided stable adhesive coatings on highly-hydrophobic surfaces composed of striated polytetrafluoroethylene ({PTFE)}, significantly enhancing proliferation of aligned cells and increasing the complexity of the produced tissue. The thickness and structure of this highly-organised tissue were similar to those observed in vivo, comprising aligned newly-deposited extracellular matrix. As such, the developed coatings can constitute a versatile biomaterial for applications in cell biology, tissue engineering, and regenerative medicine requiring serum-free conditions.