Long-chain polyunsaturated fatty acids in plasma lipids of obese children

Fatty acid composition of plasma phospholipids (PL), triglycerides (TG), and sterol esters (STE) was determined by high-resolution capillary gas-liquid chromatography in 22 obese children (age: 13.7±1.4 y, body weight relative to normal weight for height: 170±24%, mean ±SD) and compared with data obtained in 25 age-matched healthy controls. There were no differences in the levels of linoleic acid (LA, C_18∶2n-6) in any of the plasma fractions from the obese children and the controls. Obese children exhibited significantly higher values of arachidonic acid (AA, C_20∶4n-6) than controls both in PL (12.6 [2.4] vs. 8.3 [1.4], % wt/wt, [median (interquartile range)],P<0.001) and STE (7.3 [1.8] vs. 6.0 [1.1],P<0.05). Similarly, obese children showed higher values than controls for dihomo-γ-linolenic acid (DHGLA, C_20∶3n-6) in PL (4.0 [0.5] vs. 3.0 [0.6],P<0.001), TG (0.4 [0.1] vs. 0.2 [0.1],P<0.001), and STE (0.9 [0.1] vs. 0.7 [0.1],P<0.01), and for γ-linolenic acid (C_18∶3n-6) in STE (1.1 [0.2] vs. 0.8 [0.2],P<0.001). The AA/LA ratios were higher in obese children than in controls in PL (0.68 [0.16] vs. 0.42 [0.09],P<0.0005) and STE (0.16 [0.04] vs. 0.12 [0.02],P<0.05), whereas the AA/DHGLA ratios were lower in TG of obese children than in controls (3.40 [0.64] vs. 5.10 [1.75],P<0.005). Plasma glucose concentrations were inversely related to AA in TG (r=0.53,P<0.05), and plasma TG concentrations were inversely related to AA in PL and STE (r=−0.49,P<0.05 andr=−0.48,P<0.05) and to the AA/DHGLA ratios in PL (r=−0.57,P<0.01),TG (r=−0.56,P<0.01) and STE (r=−0.56,P<0.01). We conclude that the significantly higher values of n-6 long-chain polyunsaturated fatty acids (LCP) in plasma lipids of obese children than in age-matched controls may be caused by an enhanced activity of Δ6-desaturation, and we speculate that elevated fasting immunoreactive insulin seen in obese children (19.4±8.0 μU/mL) may stimulate synthesis of n-6 LCP fatty acids.     

Plasma Lipid Transfer Enzymes in Non-Diabetic Lean and Obese Men and Women

There are considerable differences in the plasma lipid profile between lean and obese individuals and between men and women. Little, however, is known regarding the effects of obesity and sex on the plasma concentration of enzymes involved in intravascular lipid remodeling. Therefore, we measured the immunoreactive protein mass of lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol-ester transfer protein (CETP) and lecithin-cholesterol acyl transferase (LCAT) in fasting plasma samples from 40 lean and 40 obese non-diabetic men and premenopausal women. Women, compared with men, had ~5% lower plasma LCAT (p < 0.041), ~35% greater LPL (p = 0.001) and ~10% greater CETP (p = 0.085) concentrations. Obese, compared with lean individuals of both sexes, had ~30% greater plasma LCAT (p < 0.001), ~20% greater CETP (p < 0.001) and ~20% greater LPL (p = 0.071) concentrations. Plasma HL concentration was not different in lean men and women. Obesity was associated with increased (by ~50%) plasma HL concentration in men (p = 0.018) but not in women; consequently, plasma HL concentration was lower in obese women than obese men (p = 0.009). In addition, there were direct correlations between plasma lipid transfer enzyme concentrations and lipoprotein particle concentrations and sizes. There are considerable differences in basal plasma lipid transfer enzyme concentrations between lean and obese subjects and between men and women, which may be partly responsible for respective differences in the plasma lipid profile.     

Vitamin D and Evening Primrose Oil Administration Improve Glycemia and Lipid Profiles in Women with Gestational Diabetes

Limited data are available assessing the effects of vitamin D and evening primrose oil (EPO) administration on markers of insulin resistance and lipid concentrations in gestational diabetes mellitus (GDM). This study was designed to evaluate the effects of vitamin D and EPO administration on insulin resistance and lipid concentrations among women with GDM. In this prospective randomized, double‐blind, placebo‐controlled clinical trial, 60 participants with GDM were divided into 2 groups of either 1000 IU vitamin D3 and 1000 mg EPO or placebo for 6 weeks. At the beginning and end of the study, fasting blood samples were obtained from the participants to measure related variables. After 6 weeks of intervention, changes in fasting plasma glucose (?3.6 ± 7.5 vs. +1.5 ± 11.4 mg/dL, P = 0.04), serum insulin concentrations (?2.0 ± 5.3 vs. +4.6 ± 10.7 µIU/mL, P = 0.004), homeostasis model of assessment (HOMA) insulin resistance (?0.5 ± 1.1 vs. +1.1 ± 2.5, P = 0.003), HOMA‐B cell function (?7.7 ± 23.3 vs. +17.4 ± 42.9, P = 0.007) and the quantitative insulin sensitivity check index (+0.01 ± 0.02 vs. ?0.01 ± 0.02, P = 0.007) in the vitamin D plus EPO group were significantly different from the placebo group. In addition, compared with the placebo, vitamin D and EPO supplementation resulted in significant reductions in serum TAG (?20.0 ± 54.3 vs. +34.3 ± 38.2 mg/dL, P < 0.001), VLDL (?4.0 ± 10.9 vs. +6.9 ± 7.6 mg/dL, P < 0.001), TC (?22.1 ± 32.6 vs. +5.3 ± 20.1 mg/dL, P < 0.001), LDL concentrations (?18.0 ± 25.5 vs. +1.8 ± 15.7 mg/dL, P = 0.001) and TC/HDL (?0.3 ± 0.4 vs. +0.3 ± 0.5 mg/dL, P < 0.001). We did not observe any significant effect of vitamin D and EPO supplementation on serum HDL concentrations. Clinical trial registration number: http://www.irct.ir : IRCT201509115623N52.     

Dehydroepiandrosterone alters lipid profiles in Zucker rats

High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair-fed (PF) group (n=6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (∼1 mmol/L) compared to lean rats (∼0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P<0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.     

Preferential loss of visceral fat following aerobic exercise, measured by magnetic resonance imaging

The aim of this study was to use whole-body magnetic resonance imaging (MRI) together with biochemical and anthropometric measurements to study the influence of regular moderate exercise with no dietary intervention on adipose tissue distribution in nonobese healthy women. We found significant decreases in both total (28.86±2.24 vs. 27.00±2.27 liters, P<0.05) and regional fat depots (visceral fat: 1.68±0.21 vs. 1.26±0.18 liters, P<0.01) using whole-body MRI despite no significant change in body weight, body mass index, or the waist-to-hip ratio. Interestingly, no changes in body fat content were found using anthropometry or impedance. There was a significant increase in high density lipoprotein cholesterol (1.58 ±0.06 vs. 1.66±0.08 mmol/L P<0.02) following exercise although there were no changes in other blood lipids such as triglycerides. In summary, moderate aerobic exercise over a period of 6 mon resulted in a preferential loss in visceral fat in nonobese healthy women, and this may help to explain some of the health benefits associated with regular and moderate physical activity.     

Effects of Dietary Coconut Oil on the Biochemical and Anthropometric Profiles of Women Presenting Abdominal Obesity

The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences (WC) >88 cm (abdominal obesity) were investigated. The randomised, double-blind, clinical trial involved 40 women aged 20–40 years. Groups received daily dietary supplements comprising 30 mL of either soy bean oil (group S; n = 20) or coconut oil (group C; n = 20) over a 12-week period, during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day. Data were collected 1 week before (T1) and 1 week after (T2) dietary intervention. Energy intake and amount of carbohydrate ingested by both groups diminished over the trial, whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged. At T1 there were no differences in biochemical or anthropometric characteristics between the groups, whereas at T2 group C presented a higher level of HDL (48.7 ± 2.4 vs. 45.00 ± 5.6; P = 0.01) and a lower LDL:HDL ratio (2.41 ± 0.8 vs. 3.1 ± 0.8; P = 0.04). Reductions in BMI were observed in both groups at T2 (P < 0.05), but only group C exhibited a reduction in WC (P = 0.005). Group S presented an increase (P < 0.05) in total cholesterol, LDL and LDL:HDL ratio, whilst HDL diminished (P = 0.03). Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity.     

Natural Rumen‐Derived trans Fatty Acids Are Associated with Metabolic Markers of Cardiac Health

Evidence suggests that industrial trans fatty acids (iTFA) impair lipid profiles while ruminant trans fatty acids (rTFA) may lower insulin resistance and blood pressure. The objective of this article was to determine if the plasma phospholipid percentage of rTFA is associated with a favorable cardiometabolic profile. We collected fasting blood samples from 200 individuals from Quebec city (QC, Canada) aged from 18 to 55 years old, including 100 obese (BMI ≥ 30 kg m^?2) and 100 non‐obese (BMI < 30 kg m^?2) men and women. Fatty acid levels in plasma phospholipids were determined using gas chromatography. After separating the subjects into two groups, according to the median percentage of rTFA in plasma phospholipids, participants in the group with higher percentages of rTFA (0.86 ± 0.24 %) had higher adiponectin levels (p = 0.01) and a lower blood pressure (systolic, p = 0.005; diastolic, p = 0.04). In contrast, concentrations in plasma phospholipids of elaidic acid, a major iTFA, are positively correlated with glycemia in non‐obese subjects (p = 0.01) and with both triacylglycerol (TAG) (p = 0.0007) and total cholesterol (TC) (p = 0.009) in obese subjects. These data suggest that rTFA may have beneficial effects on cardiometabolic risk factors conversely to their counterpart iTFA. Dietary sources of TFA should be taken into account in future cardiometabolic studies.     

Primary Hypercholesterolemia, Carotid Atherosclerosis and Insulin Resistance Among Chinese

We investigated the genetic contributions to carotid atherosclerosis and insulin resistance in Chinese patients with primary hypercholesterolemia. A family study of probands from the outpatient clinics in patients with high low-density-lipoprotein cholesterol levels was conducted. A total of 62 families (360 subjects) underwent carotid ultrasonography and insulin resistance measurement. The correlation coefficients of carotid intima-media thickness (IMT) were high among spouse, parent–offspring, and sibling pairs (0.39, 0.38 and 0.35, respectively). All insulin indices and IMT had significant estimates of heritability, of which fasting insulin had the highest heritability (0.410 ± 0.104, P = 0.0001), followed by homeostasis model assessment (HOMA) (0.395 ± 0.108, P = 0.0001). The estimated heritability of IMT was significant (0.185 ± 0.103, P = 0.025) but not of plaque score. Bivariate genetic coefficient between IMT and HOMA was 0.569 ± 0.292, while the environmental coefficient was 0.028 ± 0.103. The study confirms a relationship between insulin resistance and atherosclerosis and, in particular, between insulin resistance and the thickening of the arterial wall. Moreover, it shows that genetics influence both insulin resistance and atherosclerosis, implying that the management of insulin resistance may benefit the prevention of atherosclerotic disease in familial hypercholesterolemia.     

Influence of Interesterification of a Stearic Acid-Rich Spreadable Fat on Acute Metabolic Risk Factors

Chemical and enzymatic interesterification are used to create spreadable fats. However, a comparison between the two processes in terms of their acute metabolic effects has not yet been investigated. A randomised crossover study in obese (plasma TAG > 1.69 mmol/L, and BMI > 30 (BMI = kg/m²) or waist circumference > 102 cm, n = 11, age = 59.3 ± 1.8 years) and non-obese (plasma triacylglycerol (TAG) < 1.69 mmol/L, and BMI < 30  or waist circumference < 102 cm, n = 10, age = 55.8 ± 2.2 years) men was undertaken to compare the effects of chemical versus enzymatic interesterification on postprandial risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). TAG, cholesterol, glucose, insulin and free fatty acid concentrations were measured for 6 h following consumption of 1 g fat/kg body mass of non-interesterified (NIE), chemically interesterified (CIE), enzymatically interesterified (EIE) stearic acid-rich fat spread or no fat, each with 50 g available carbohydrate from white bread. Interesterification did not affect postprandial glucose, insulin, free fatty acids or cholesterol (P > 0.05). Following ingestion of NIE, increases in serum oleic acid were observed, whereas both oleic and stearic acids were increased with CIE and EIE (P < 0.05). While postprandial TAG concentrations in non-obese subjects were not affected by fat treatment (P > 0.05), obese subjects had an 85% increase in TAGs with CIE versus NIE (P < 0.05). The differences in TAG response between non-obese and obese subjects suggest that interesterification may affect healthy individuals differently compared to those already at risk for T2D and/or CVD.     

Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue

Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the “one true” endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a “good candidate” as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA’s effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments we employed a DHEA and a pair-fed (PF) group (n=6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18∶1) acid than their PF controls. Likewise, 18∶1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.     

Effect of human mammary MX-1 tumor on plasma free fatty acids in fasted and fasted-refed nude mice

We hypothesized that tumor-bearing (TB) nude mice, because they are reported to have no detectable, circulating tumor necrosis factor (TNF)/cachectin, would regulate their plasma free fatty acid (FFA) levels normally when fasted and refed. We compared levels of individual plasma FFA in response to fasting (24 hr) and to refeeding (for 20 hr after fasting) a fat-free, 65% sucrose diet in control, nude mice and in mice bearing 1.3±0.4 g MX-1 tumors. Total plasma FFA levels were typically high in 24-hr fasted mice [mean concentrations in μM±SE (n); controls 515±63 (6); TB, 625±63 (6)]. FFA levels were reduced by 65% in each group in response to refeeding. Each major plasma FFA species fell in response to refeeding, except arachidonate, which did not change significantly (fastedvs. fasted-refed concentrations) in either controls or TB mice. In refed mice, the molar FFA ratio of oleate to linoleate rose; however, that of oleate to arachidonate fell markedly. TB nude mice had normal appetites. We conclude that all species of FFA were mobilized from adipose tissue in a normal manner in TB nude mice; therefore, regulation of adipose triacylglycerol fatty acid mobilization (as plasma FFA) by dietary sugar is probably not affected by MX-1 tumor growth in these mice. Our findings are consistent with the hypothesis that nude mice may be unable to secrete TNF/cachectin in response to tumor growth, but they do not establish whether or not endogenous, circulating TNF/cachectin increases FFA mobilization in any TB animal.     

Relationships between the fatty acid composition of muscle and erythrocyte membrane phospholipid in young children and the effect of type of infant feeding

Muscle membrane fatty acid (FA) composition is linked to insulin action. The aims of this study were to compare the FA composition of muscle and erythrocyte membrane phospholipid in young children; to investigate the effect of diet on these lipid compositions; and to investigate differential incorporation of FA into muscle, erythrocyte and adipose tissue membrane phospholipid, and adipose tissue triglyceride. Skeletal muscle biopsies and fasting blood samples were taken from 61 normally nourished children (15 males and 16 females), less than 2 yr old (means ±SE, 0.80±0.06 yr), undergoing elective surgery. Adipose tissue samples were taken from 15 children. There were significant positive correlations between muscle and erythrocyte docosahexaenoic acid (DHA) (r=0.44, P<0.0001), total n−3 polyunsaturated fatty acids (PUFA) (r=0.39, P=0.002), and the n−6/n−3 PUFA ratio (r=0.39, P=0.002). Adipose tissue triglyceride had lower levels of long-chain PUFA, especially DHA, than muscle and erythrocytes (0.46±0.18% vs. 2.44±0.26% and 3.17±0.27%). Breast-fed infants had higher levels of DHA than an age-matched group of formulafed infants in both muscle (3.91±0.21% vs. 1.94±0.18%) and erythrocytes (3.81±0.10% vs. 2.65±0.23%). The results of this study show that (i) erythrocyte FA composition is a reasonable index of muscle DHA, total n−3 PUFA, and the n−6/n−3 PUFA ratio; (ii) breast feeding has a potent effect on the FA composition of all these tissues; and (iii) there is a wide range in long-chain PUFA levels in muscle, erythrocytes, and adipose tissue.     

Oxidation of intracellular and extracellular fatty acids in skeletal muscle

Fatty acids are a major fuel for many tissues, and abnormal utilization is implicated in diseases. However, tissue fatty acid oxidation has not been determined reliably in vivo. Furthermore, fatty acid oxidation has not been partitioned into intracellular and extracellular components. In this report, a one‐pool model is described that enables direct quantitation of fluxes of intracellular and plasma fatty acids to mitochondria in skeletal muscle using dual stable isotopes and liquid chromatography/electrospray ionization ion‐trap tandem mass spectrometry technology. It is validated by the determination of palmitate oxidation by skeletal muscle in lean and obese rats and the regulation by insulin. Resting postabsorptive intramyocellular and plasma palmitate oxidation by the gastrocnemius muscle was determined to be 3.47 ± 0.8 and 2.06 ± 0.5 nmol/g/min in lean and 6.96 ± 1.8 and 1.34 ± 0.2 nmol/g/min in obese rats, respectively. In obese rats, hyperinsulinemia (1 nmol/L) suppressed intramyocellular (by 59 ± 5% to 2.88 ± 0.3 nmol/g/min; p <0.05) but not plasma (1.41 ± 0.14 nmol/g/min; p >0.05) palmitate oxidation. The fractional turnover rate of palmitoylcarnitine (0.34 ± 0.1/min vs. 0.83 ± 0.2/min; p <0.05) was also suppressed by insulin in obese rats. In obese and lean rats, 83 and 51%, respectively (p = 0.08), of plasma fatty acids traverse the triacylglycerol pool before being oxidized. The results demonstrated that the methodology is feasible and sensitive to metabolic alterations and thus can be used to study fatty acid utilization at tissue level in vivo in a compartmentalized manner for the first time.     

Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans

Data on the effect of dietary arachidonic acid (AA) (20∶4n-6) on the synthesis of thromboxane and prostacyclin (PGI₂) in humans are lacking. We measured the effect of 1.5 g/d (ca. 0.5 en%) of 20∶4n-6 added isocalorically to a stabilization (low-AA) diet on the excretion of 11-dehydrothromboxane B₂ (11-DTXB₂) and 2,3-dinor-6-oxo-PGF_1α (PGI₂-M). In a crossover design, 10 healthy men, living in a metabolic unit, were fed a diet (low-AA) containing 210 mg/d of 20∶4n-6 for 65 d and an identical diet (high-AA) that contained 1.5 g/d of additional 20∶4n-6 for 50 d. Three-day urine pools were collected at the end of each dietary period and analyzed for eicosanoids by gas chromatography-electron capture negative ion-tandem mass spectrometry. Mean excretion of 11-dehydrothromboxane B₂ was 515±76, 493±154, and 696±144 ng/d (SD; n=10) during the acclimation (15 d) low-AA diet and high-AA diet periods, respectively (41% increase from low-AA to high-AA diet, P=0.0037); mean excretion of PGI₂-M was 125±40, 151±36, and 192±55 ng/d (SD; n=10) during acclimation (15 d) low-AA and high-AA diets, respectively (27% increase from low-AA to high-AA diets; P=0.0143). Thus, both the metabolites of thromboxane and PGI₂ increase on the high-AA diet. Furthermore, both indicated changes in metabolite excretion may be associated with measurable effects on several physiologically significant cellular functions, such as platelet aggregation in vivo and inflammation in response to immune challenges.     

Chronic free fatty acid infusion in rats results in insulin resistance but no alteration in insulin-responsive glucose transporter levels in skeletal muscle

To investigate the mechanism by which free fatty acids (FFA) affect glucose uptake, we studied the effect of chronic elevation (24 h) of plasma FFA in rats on whole body glucose disposal and glucose utilization index (GUI) in the basal state and under a euglycemic hyperinsulinemic clamp in relation to the amount of insulin-responsive glucose transporter (IRGT, i.e., GLUTU), protein in different muscles (oxidative and glycolytic) and adipose tissue. Infusion of Intralipid in the basal state led to a∼40% increase in whole body glucose uptake and a∼250% increase in GUI in adipose tissue as compared to control rats. There was no change in the amount of IRGT protein in any of the muscle types whereas in fat depots it was either unchanged or decreased. Under moderate or supraphysiological hyperinsulinemia, increment of whole body glucose disposal was significantly lower in Intralipid perfused rats when compared to controls (∼110 μU/mL: 0.7±0.1 vs. 1.3±0.1 mg/min,P<0.02; ∼1000 μU/mL: 3.0±0.2 vs. 3.9±0.4 mg/min,P<0.02). Under moderate hyperinsulinemia stimulation, GUI was significantly reduced in different muscles and adipose tissue as compared to controls. We conclude that peripheral insulin resistance which occurs after elevation of plasma FFA levels does not seem to be explained by changes in the amount of IRGT protein in either oxidative or glycolytic skeletal muscle. Thus fatty acid infusion appears to be associated with a defect in IRGT translocation to the plasma membrane, fusion with the membrane, or intrinsic activity.     

Plasma kinetics of a cholesterol-rich emulsion in young, middle-aged, and elderly subjects

Low density lipoprotein (LDL) plasma concentration is increased in the elderly. In this group, the incidence of coronary artery disease (CAD) is greater and LDL remains an important risk factor for CAD development. In this study, the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors was studied in 10-subject groups of the elderly (70±4 yr), middle-aged (42±5 yr) and young (23±2 yr). All were normolipidemic, nonobese, nondiabetic subjects who did not have CAD. The emulsion was labeled with ¹⁴C-cholesteryl oleate and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 h to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate (FCR, in h⁻¹). FCR of the emulsion label was smaller in elderly compared to young subjects (0.032±0.035 and 0.071±0.049 h⁻¹, respectively; mean±SD, P<0.05). FCR of the middle-aged subjects (0.050±0.071 h⁻¹) was intermediate between the values of the elderly and young subjects, although not statistically different from them. A negative correlation was found between the emulsion FCR and subjects’ age (r=−0.47, P=0.008). We conclude that aging is accompanied by progressively diminished clearance of the emulsion cholesterol esters and, by analogy, of the native LDL.     

Decreased serum adiponectin in adolescents and young adults with familial primary hypercholesterolemia

Decreased serum adiponectin is associated with dyslipidemia. However, serum adiponectin status has never before been studied in patients with familial-related severe primary hypercholesterolemia (FRSPH). The aim of this study is to measure serum adiponectin level in a group of young patients with FRSPH and determine its correlation with insulin-resistant status. Twenty-three patients with FRSPH [average LDL-cholesterol (LDL-C)=250.8 (190–610) mg/dL] without clinical manifestations of metabolic syndrome as well as 46 healthy (control) adolescents and young adults (<30 yr old) were included. The serum adiponectin, fasting sugar, insulin, lipids, systolic and diastolic blood pressure (SBP and DBP), and anthropometrical indices such as body mass index and waist circumference were obtained. The homeostasis model assessment (HOMA) was calculated to estimate the insulin resistant status. Compared with healthy controls, patients with FRSPH had a significantly lower mean serum adiponectin level (7.7±1.8 μg/mL vs. 10.1±4.3 μg/mL, P=0.013). After adjustment for HOMA and associated covariates, multiple linear regression analysis showed that patients with FRSPH are significantly associated with hypoadiponectinemia. Compared with healthy controls, patients with FRSPH had a significantly lower mean serum adiponectin level (7.7±1.8 μg/mL vs. 10.1±4.3 μg/mL, P=0.013). After adjustment for HOMA and associated covariates, multiple linear regression analysis showed that patients with FRSPH are significantly associated with hypoadiponectinemia. The serum adiponectin levels are lower in young patients with FRSPH without clinical manifestations of metabolic syndrome. The mechanism of hypoadiponectinemia in patients with FRSPH is probably independent of insulin resistance.     

EPA,but not DHA,decreases mean platelet volume in normal subjects

The first indication of platelet activation is an increase in mean platelet volume (MPV). n−3 FA are known to inhibit platelet function and to reduce the risk for coronary heart disease. The purpose of this study was to determine the effects of FPA and DHA on MPV. Healthy subjects received olive oil placebo for 4 wk and then were randomly assigned to receive 4g of ethyl esters of either safflower oil (n=11), EPA (n=10), or DHA (n=12) for 4 wk. At the end of placebo run-in and treatment periods, MPV (fL; mean±SEM) and platelet count (PLT-CT; 10³/μL blood) were measured in the basal state and after ex vivo stimulation with collagen (10 μg/mL), cold (4°C), and heat (37°C). Unlike DHA, EPA lowered MPV as compared with safflower oil (7.2±0.1 vs. 7.5±0.1 fL; P<0.05) and raised PLT-CT (211±18 vs. 192±18 10³/μL; P<0.05) in the fasting state. Collagen and cold significantly increased MPV whereas heat lowered MPV regardless of treatment. All stimuli decreased PLT-CT. EPA significantly increased platelet EPA (0.2±0.1 vs. 3.3±0.4%) and docosapentaenoic acid (DPA; 2.2±0.3 vs. 2.9±0.3%) concentrations, but not DHA. DHA treatment significantly increased DHA (1.4±0.2 vs. 4.1±0.5%) and DPA (2.0±0.4 vs. 3.0±0.4%) concentrations, but not EPA. In conclusion, EPA, but not DHA, reduces platelet activation, an early step in platelet aggregation.     

Sex and Depot Differences in Palmitoleic Acid Content of Human Blood and Fat

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test–retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.     

The esterified plasma fatty acid profile is altered in early HIV-1 infection

Previous studies have shown that alterations in micronutrient utilization occur in patients with Acquired Immune Deficiency Syndrome. In this study, total plasma fatty acid composition was measured in 36 homosexual men infected with the Human Immunodeficiency Virus 1 (HIV-1) and in 17 HIV-1 seronegative homosexual men in order to evaluate differences associated with early HIV-1 infection. Immunologic assessment included CD4 cell number count and lymphocyte blastogenesis in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). The mean total amount of ω6 polyunsaturated fatty acids (18∶2 and 20∶4) was significantly lower in the HIV-1 seropositive subjects (38±8.1% SD) as compared to HIV-1 seronegative subjects (43±4.2%;P=0.0027). This was also reflected in a higher level of total saturated fatty acids (16∶0 and 18∶0) in HIV-1 seropositive subjects (30±2.2%vs. 26±2.8%;P=0.0001). The ratio of linoleic to arachidonic acid (18∶2 to 20∶4) was higher in the HIV-1 seronegative group (6.76±4.88) compared to the HIV-1 seronegative group (4.86±1.37;P=0.0213). The response to PHA in seropositive subjects correlated inversely with total plasma ω6 fatty acids (r=−0.36;P=0.027), and directly with the 18∶2 to 20∶4 ratio (r=0.33;P=0.046). CD4 cell counts and the response to PWM did not correlate with plasma fatty acid levels in HIV-1 seropositive subjects. We conclude that early HIV-1 infection is associated with lower plasma ω6 polyunsaturated fatty acids, notably arachidonic acid, than are controls, and that the changes in the plasma fatty acid profile correlate with some indices of immune function.