Plasma phospholipid fatty acid composition as a biomarker of habitual dietary fat intake in an ethnically diverse cohort

Background and aimAs an evaluation of fatty acid intake measurement, our aim was to examine associations between diet and plasma phospholipid (PL) fatty acids, and whether these were modified by age, sex, country of birth, fasting status, use of cholesterol-lowering medication, body size, chronic disease and other lifestyle factors.Methods and resultsCross-sectional analysis of plasma PL fatty acid composition and dietary fatty acid intake over 12 months from a 121-item food frequency questionnaire (FFQ) in 4439 men and women aged 40–69 years, born in Australia, Greece or Italy. Crude correlation coefficients ranged from 0.18 to 0.40; and corrected correlation coefficients from 0.38 to 0.78 for total monounsaturated, polyunsaturated, n-6, n-3 fatty acids, oleic acid, linoleic acid, EPA and DHA. Weaker associations were observed for other fatty acids. The associations did not vary significantly by fasting status, use of lipid lowering medication or alcohol intake, but for some fatty acids did vary by sex, age, body mass index, country of birth, smoking and previous heart attack or diabetes.ConclusionsThe FFQ provides useful information on intakes of mono- and polyunsaturated fatty acids. Correlations did not differ by fasting status, or use of lipid-lowering medication.     

Energy restriction dilutes the changes related to dietary fat type in membrane phospholipid fatty acid composition in rats

To investigate liver cell membrane phospholipid (PL) fatty acid (FA) composition in response to the consumption of different types of dietary fat and graded levels of energy intake, rats were fed for 10 weeks on a diet containing either fish oil, safflower oil, or beef tallow. Within each dietary fat group, subgroups were either provided free access to food or energy-restricted to 85% or 70% of the ad libitum intake by reducing the dietary carbohydrate content while keeping other macronutrient intakes constant. Higher (P < .05) proportions of docosahexaenoic acid, linoleic acid, and monounsaturated FA were observed in the membrane PL of the fish oil, safflower oil, and beef tallow groups, respectively, resembling the FA composition in the diets. However, such modifications of dietary FA composition in, membrane PL FA were influenced by body energy status. The higher docosahexaenoic acid and total n-3 FA content in phosphatidylcholine (PC), sphingomyelin (SPH), and phosphatidylserine (PS) of the ad libitum fish oil group compared with the other dietary groups no longer existed when energy supply was restricted. Therefore, reducing energy intake tended to dilute the changes of membrane PL FA composition occurring as a function of dietary FA composition. These data suggest that the influence of dietary fat type on cellular structure and perhaps function becomes increasingly important with progressively positive energy balance.     

Erythrocyte membrane phospholipid composition is related to hyperinsulinemia in obese nondiabetic women: effects of weight loss

The complex mechanisms by which obesity predisposes to insulin resistance are not clearly understood. According to a cell membrane hypothesis of insulin resistance, the defects in insulin action could be related to changes in membrane properties. The purpose of this work was to examine the relationship between 2 markers of insulin resistance (fasting plasma insulin [FPI] and homeostasis model assessment [HOMA IR]) and erythrocyte membrane lipid composition. In the first cross-sectional study, 24 premenopausal nondiabetic overweight women (body mass index [BMI], 32.5 +/- 0.9 kg/m(2); age, 35.7 +/- 2.2 years) were compared to 21 lean healthy women (BMI, 21 +/- 0.4 kg/m(2); age, 35.4 +/- 2.2 years). The second study examined whether a 3-month diet-induced weight loss, which usually improves insulin resistance, could also affect the membrane phospholipid (PL) composition and fluidity in the overweight group. Overweight women had significantly higher FPI levels (P <.0001), HOMA IR (P <.0001), membrane sphingomyelin (SM) (P <.05), and cholesterol (P <.05) contents than lean women. Baseline FPI and HOMA IR were positively correlated with membrane SM (P <.005), phosphatidylethanolamine (PE) (P <.005), and phosphatidylcholine (PC) (P <.05) contents, and negatively with phosphatidylinositol (PI) (P <.05) contents in the whole population. Multivariate regression analyses showed that 2 membrane parameters, PE and SM, were among the independent predictors of FPI or HOMA IR in the whole population, but also in the lean and the obese groups separately. Intervention induced a significant reduction in body weight (-5.7% +/- 0.7%), fat mass (-11.3% +/- 1.4%), and FPI (-10.2% +/- 5.4%). An improvement in membrane lipid composition was only observed in the insulin resistant subgroup (FPI > 9.55 mU/L). The reduction in FPI or HOMA IR was directly associated with reduction in SM and PE contents, a finding independent of the reduction in fat mass. A stepwise multiple regression analysis indicated that the changes in SM accounted for 26.6% of the variance in the changes in FPI as an independent predictor, with the changes in fat mass and PE as other determinants (27.8% and 20%, respectively, adjusted r(2) =.704, P <.0001). These results suggest that the abnormalities in the membrane PL composition could be included in the unfavorable lipid constellation of obesity which correlated with impaired insulin sensitivity.     

Ethanol-induced alterations in erythrocyte membrane phospholipid composition

Ethanol's effects on erythrocyte membrane lipid composition were examined in male squirrel monkeys divided into three groups receiving three different regimens: Controls were fed a chemically defined liquid diet, and low and high ethanol primates were given diets with vodka substituted isocalorically for 12% and 24% of calories, respectively. After membrane lipid extraction, phospholipid mass, class composition, and fatty acid profiles were measured in each group. Although there were no differences in the total phospholipid mass, the low ethanol primates had significantly elevated phosphatidylethanolamine in their membranes as compared with the other monkeys. Membrane phospholipid fatty acid profiles showed no differences among the three groups. There were also no differences in the animals' plasma liver enzymes. Results of this investigation suggest that, despite the absence of nutritional deficiencies and liver malfunction, low amounts (12%) of dietary ethanol cause elevations in phosphatidylethanolamine that may represent a specific change in the membrane's inner leaflet where this phospholipid is located. These results may have clinical significance because ethanol-induced modifications in membrane lipids may contribute to alterations in fluidity and lead to pathologic changes in function.     

Erythrocyte deformability in diabetes and erythrocyte membrane lipid composition

Erythrocyte deformability was assessed in 40 diabetic patients, 24 insulin-dependent (IDD) and 16 non-insulin-dependent (NIDD), by measuring the initial filtration flow rate of whole blood, isolated red blood cells (RBC), and isolated RBC membranes with the Hanss hemorheometer, and its relationship to the plasma and ghost membrane lipid composition was investigated. RBC deformability was significantly reduced, whereas the deformability of the isolated RBC membranes did not differ significantly from the controls. In the plasma, the triglycerides were high, the high-density lipoprotein (HDL) cholesterol was reduced, and the ratio of total cholesterol over HDL cholesterol was high as compared with the controls. The RBC lipid composition expressed in mumol lipids/10(10) RBC showed significantly lower levels of free cholesterol, sphingomyelines, and phosphatidylcholine, which are the lipids principally located on the outer layer of the RBC membranes. These data suggest that in both IDD and NIDD patients, there may be a relation between these modifications in the RBC lipid composition and rheological impairment of the RBC.     

Erythrocyte and glomerular C4d deposits as a biomarker for active lupus nephritis

Introduction

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and histologically evident even in those without clinical manifestations of renal disease.

Development of MR quantified pancreatic fat deposition as a cancer risk biomarker

Background

Excess body adiposity is associated with increased risk of pancreatic cancer, and in animal models excess intra-pancreatic fat is a driver of pancreatic carcinogenesis. Within a programme to evaluate pancreatic fat and PC risk in humans, we assessed whether MR-quantified pancreatic fat fraction (PFF) was ‘fit for purpose’ as an imaging biomarker.

Development of dietary obesity in rats: influence of amount and composition of dietary fat.

This study was conducted to examine long-term effects of amount and type of dietary fat on body weight and body composition. Adult male Wistar rats were fed high fat (HF; 60% of calories) or low fat (LF; 20% of calories) diets for 28 weeks. Half of the rats in each condition received diets with saturated fat (lard) (S) and the remainder received diets with polyunsaturated fat (corn oil) (U). From 28-39 weeks, HF rats were switched to LF diets (fat type remained constant). From 40-50 weeks, previously HF fed rats were weight-matched to rats in the LF fed groups. HF rats became fatter than LF rats during weeks 1-28 and remained heavier and fatter from weeks 28-39. During weeks 1-28, type of dietary fat had no effect on total body fat in either HF or LF rats, but during period 2 (weeks 28-39), U rats were heavier and fatter than S rats. There was some indication that U diets were associated with greater accumulation of fat in subcutaneous adipose tissue depots than S diets. From 40-50 weeks, rats previously fed the HF diet required less food to maintain their body weight than did LF diet rats. In summary, these results suggest that although both amount and type of dietary fat can affect body weight and body composition, the effects of the type of fat are less than those of amount of dietary fat.     

Serum lipid profile as a biomarker of intra-pancreatic fat deposition: A nested cross-sectional study

Background and aimsThe relationship between intra-pancreatic fat deposition (IPFD) and lipid profile has been investigated in individuals with obesity and/or type 2 diabetes, but not in healthy non-obese individuals and those after acute pancreatitis. The aim of the study was to investigate the association between serum lipid profile and IPFD in the latter individuals and to determine the effect of abdominal fat distribution and other covariates.Methods and resultsA total of 90 individuals with a history of acute pancreatitis as well as 23 healthy non-obese individuals participated in the study. Magnetic resonance imaging was used to quantify IPFD and visceral-to-subcutaneous fat volume ratio, followed by fasting state measurement of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TC/HDL-C ratio, and triglycerides. In healthy non-obese individuals, IPFD was not significantly associated with any of the studied markers. In individuals after acute pancreatitis, IPFD was significantly associated with triglycerides in both unadjusted (β = 0.360; 95% CI, 0.090–0.629; p = 0.009) and adjusted models, with a β-coefficient of 0.280 [(95% CI, 0.016–0.545); p = 0.038] in the most adjusted model. Also, IPFD was significantly associated with TC/HDL-C ratio in both unadjusted (β = 0.336; 95% CI, 0.045–0.626; p = 0.024) and adjusted models, with a β-coefficient of 0.375 [(95% CI, 0.090–0.660); p = 0.010] in the most adjusted model. Multiple regression yielded triglycerides, but not TC/HDL-C ratio, as a significant marker of IPFD in individuals after acute pancreatitis.ConclusionsSerum lipid profile is not associated with IPFD in healthy non-obese. Triglycerides, but not other components of lipid profile, is a promising biomarker for IPFD in individuals following acute pancreatitis.     

Novel high-performance liquid chromatography for determination of membrane phospholipid composition of rat hepatocytes

We have developed a new, quick and efficient method of high-performance liquid chromatography (HPLC) for the isolation and quantitative determination of phospholipids in hepatocyte membranes. A silica gel column was used for the isolation and determination, and an isocratic mixture of acetonitrile, methanol and 85% phosphoric acid (130:5:1.7, v/v/v) was used as a mobile phase. Six kinds of phospholipids, i.e. phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphinogomyelin (SPH), in this order, were completely isolated within 45 min. The phospholipid composition of sinusoidal membrane vesicles (SMV) and canalicular membrane vesicles (CMV) obtained from rat liver, as well as of human erythrocyte ghosts were determined by this HPLC method. The level of SPH in CMV was significantly higher than that in SMV, and the level of PC in CMV was significantly lower than that in SMV. These results were considered attributable to the low fluidity of CMV. The phospholipid composition of human erythrocyte membrane was different from that of rat SMV and CMV. The present technique is suitable for quantitative determination of phospholipids in cell membranes.     

Erythrocyte as a biological sensor

The erythrocytes ability of sensing the local oxygen gradient through the hemoglobin conformation, along with changes in nitric oxide mobilization and vasomotor repercussions at the microcirculation, were reviewed in detail in this article. Different approachs trying to explain the erythrocyte death were additionally documented. Also, the influence of several types of molecules (vasoactive, oxidant/reductor) on the erythrocyte roles as sensor of (i) oxygen tissue needs, (ii) blood viscosity and myogenic environment, (iii) and inflammatory conditions were mentioned in order to highlight its physiologycal function and substitute the erroneous idea of the erythrocyte being simply a hemoglobin sac content.     

Progesterone receptor membrane component 1 as a potential prognostic biomarker for hepatocellular carcinoma

AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.     

Rat brain fatty acid composition: effect of dietary fat and age.

The polyunsaturated fatty acid composition of human brain changes, as well as progressively decreases, with age. To determine if whole brain rat lipid shows similar changes with age, rats born to mothers fed semi-synthetic diets were raised on the same diet as their mothers for varying periods prior to sacrifice. Whole brain lipid composition was determined for female offspring, fed diets containing 20% w (by weight) of either lard or safflower oil, from age 6 days to 730 days. The percentage of 20:4omega6 and 22:6omega6 decreased with age; as in man these changes were compensated for largely by increases in 18:1omega9. In contrast, 22:6omega3 rose gradually from 6 to 730 days of age. Varying the degree of unsaturation and/or the amount of dietary fat, with the exception of lard, did not influence the fatty acid composition of whole brain lipid or of the two major phospholipids, phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC). Lard was found to contain trace amounts of 22:5omega3; this acid was avidly retained in the brain accompanied by corresponding decreases in 22:5omega6. The functional significance of the observed age-related brain lipid changes is unknown; it is likely that the lipid changes are in some way related to the deterioration of the central nervous system with time.     

Novel high-performance liquid chromatography for determination of membrane phospholipid composition of rat hepatocytes.

We have developed a new, quick and efficient method of high-performance liquid chromatography (HPLC) for the isolation and quantitative determination of phospholipids in hepatocyte membranes. A silica gel column was used for the isolation and determination, and an isocratic mixture of acetonitrile, methanol and 85% phosphoric acid (130:5:1.7, v/v/v) was used as a mobile phase. Six kinds of phospholipids, i.e. phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphinogomyelin (SPH), in this order, were completely isolated within 45 min. The phospholipid composition of sinusoidal membrane vesicles (SMV) and canalicular membrane vesicles (CMV) obtained from rat liver, as well as of human erythrocyte ghosts were determined by this HPLC method. The level of SPH in CMV was significantly higher than that in SMV, and the level of PC in CMV was significantly lower than that in SMV. These results were considered attributable to the low fluidity of CMV. The phospholipid composition of human erythrocyte membrane was different from that of rat SMV and CMV. The present technique is suitable for quantitative determination of phospholipids in cell membranes.     

Early growth restriction, membrane phospholipid fatty acid composition, and insulin sensitivity

An animal model of protein restriction during pregnancy and lactation with subsequent dietary fatty acid manipulation was used to investigate the association between poor early growth, defective unsaturated fatty acid handling, and later disease. Both control and early growth-restricted animals fed a diet rich in saturated fatty acids showed a doubling of the plasma insulin levels as well as a reduced degree of unsaturation in liver and skeletal muscle membrane phospholipids compared with animals fed diets rich in unsaturated fatty acids. The skeletal muscle of early growth-restricted animals weaned onto a saturated fat diet had reduced proportions of 22:6n-3 and increased proportions of 18:1n-9. This reduction in 22:6n-3 is similar to that observed in Pima Indians, a population with a high prevalence of type 2 diabetes.     

Mutational alteration of membrane phospholipid composition and voltage-sensitive ion channel function in paramecium.

A behavioral mutant of Paramecium tetraurelia (baA) has been isolated that has an abnormal response when placed in solutions containing Ba2+. This mutant is shown here to have a dramatic alteration of the sphingolipid and phosphonolipid composition of its ciliary membrane. This biochemical defect is present in independently isolated alleles at baA locus and segregates in crosses with the behavioral phenotype. Electrophysiologically, the mutation reduces significantly conductance of both voltage-sensitive Ca2+ channels and voltage-sensitive K+ channels. When the mutant is grown in sterol-supplemented medium, its behavior, electrophysiological properties, and lipid composition are hardly distinguishable from wild type grown under similar conditions. This mutant then, provides strong evidence that membrane lipids significantly influence the function of the membrane molecules responsible for the generation of action potentials.     

Influence of dietary fat on the lipid composition of perirenal adipose tissue in rats

The influence of dietary fat on the composition of perirenal adipose tissue was studied in Wistar rats fed three experimental semisynthetic, isocaloric diets containing different qualities of fat (olive oil, butter and medium chain triglycerides + corn oil). Under these experimental conditions, the saturation index reflects the percentage of fatty acids supplied by each diet; this index was highest in animals fed the diet containing butter and lowest in the group in which olive oil was the dietary fat source. The amount of linoleic acid (the major component of the diunsaturation index) supplied by the diet is directly paralleled by levels of this fatty acid in perirenal adipose tissue, whereas the monounsaturation index in adipose tissues, considered an indicator of the dietary supply of monounsaturated fatty acids in the rat, failed to show a clearly proportional relationship between intake and perirenal adipose tissue levels.     

Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition

Nine adults took two 7-day diets of standardised energy and total fat content, but with a dietary polyunsaturated/saturated fat ratio of less than 0.3 and greater than 3.0 respectively, while adhering to their daily routine. Blood was drawn on 6 occasions between 09.00 and 22.45 h on the final day of each dietary period for factor VII activity (VIIc), factor VII antigen (VIIag) and lipoprotein lipid concentrations. Diurnal variation was described for each variable in terms of its deviation from the individual's daily mean value at each time point across the day. Plasma triglyceride remained low until after the midday meal, whereafter a marked rise was sustained into the later evening. Plasma VIIc declined until early afternoon, but showed a marked rise in the late afternoon. Plasma VIIag showed no significant diurnal variation. Changes in plasma triglyceride concentration during the day were related positively to changes in VIIc about 160 min later, but not to VIIc at other time points. This effect of postprandial triglyceridaemia on VIIc persisted after allowance for the effect of VIIag on VIIc. Dietary fat composition did not influence VIIc or VIIag. The results suggested an acute but evanescent effect of triglyceride-rich lipoproteins on the reactivity of factor VII, irrespective of their lipid core composition.