An Oral Mixed Fat Load Is Followed by a Modest Anti-inflammatory Adipocytokine Response in Overweight Patients with Metabolic Syndrome

We investigated the postprandial changes in plasma levels of adipocytokines in overweight patients with metabolic syndrome after an oral fat load. After an oral fat load and during a prolonged fast, blood was drawn at 0, 2, 3, 4 and 8 h for measurement of adiponectin, adipsin, cathepsin S, chemerin, hepatic growth factor, interferon‐γ‐inducible protein‐10, leptin, macrophage chemoattractant protein‐1, macrophage migration inhibitory factor, nerve growth factor, retinol binding protein‐4, resistin, serum amyloid A1, tissue inhibitor of metalloproteinase‐1 and thrombopoietin using a microbead‐based Luminex assay. Area under the curves (AUC) were calculated and compared. Plasma adiponectin levels were higher after an oral fat load compared to fasting at t = 2 h (950 ± 513 vs. ?1,881 ± 713 ng/ml) while the plasma levels for adipsin (?9 ± 5 vs. 16 ± 5 ng/ml), chemerin (?122 ± 35 vs. 13 ± 21 ng/ml), SAA‐1 (?391 ± 213 vs. 522 ± 173 ng/ml) and TPO (?335 ± 144 vs. 622 ± 216 ng/ml) were lower after an oral fat load compared to fasting. The baseline corrected AUC for IP‐10 was higher after fat load compared to fasting (median ?116 pg h/ml; IQR ?270 to 10 vs. ?21 pg h/ml; IQR ?136 to 418 (p = 0.047). In conclusion, in overweight male subjects with the metabolic syndrome, an oral fat load is accompanied with a modest anti‐inflammatory response of adipose tissue‐derived adipocytokines.     

Simple,Rapid Lipidomic Analysis of Triacylglycerols in Bovine Milk by Infusion-Electrospray Mass Spectrometry

Bovine milk is a complex mixture of lipids, proteins, carbohydrates, and other factors of which lipids comprise 3–5% of the total mass. Rapid analysis and characterization of the triacylglycerols (TAG) that comprise about 95% of the total lipid is daunting given the numerous TAG species. In the attached methods paper, we demonstrate an improved method for identifying and quantifying TAG species by infusion-based “shotgun” lipidomics. Because of the broad range of TAG species in milk, a single internal standard was insufficient for the analysis and required sectioning the spectrum into three portions based upon mass range to provide accurate quantitation of TAG species. Isobaric phospholipid interferences were removed using a simple dispersive solid-phase extraction step. Using this method, > 100 TAG species were quantitated by acyl carbon number and desaturation level in a sample of commercially purchased bovine milk.     

Dynamic Assessment of Functional Lipidomic Analysis in Human Urine

The development of enabling mass spectrometry platforms for the quantification of diverse lipid species in human urine is of paramount importance for understanding metabolic homeostasis in normal and pathophysiological conditions. Urine represents a non‐invasive biofluid that can capture distinct differences in an individual's physiological status. However, currently there is a lack of quantitative workflows to engage in high throughput lipidomic analysis. This study describes the development of a MS/MS^ALL shotgun lipidomic workflow and a micro liquid chromatography–high resolution tandem mass spectrometry (LC–MS/MS) workflow for urine structural and mediator lipid analysis, respectively. This workflow was deployed to understand biofluid sample handling and collection, extraction efficiency, and natural human variation over time. Utilization of 0.5 mL of urine for structural lipidomic analysis resulted in reproducible quantification of more than 600 lipid molecular species from over 20 lipid classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In summary, the high‐throughput functional lipidomics workflow described in this study demonstrates an impressive robustness and reproducibility that can be utilized for population health and precision medicine applications.     

Effect of Interesterification of Palmitic Acid-rich Triacylglycerol on Postprandial Lipid and Factor VII Response

The process of interesterification results in changes in triacylglycerol (TAG) structure and is used to increase the melting point of dietary fats. The acute health effects of this process on palmitic acid-rich fats are uncertain with regard to postprandial lipemia, insulin and factor VII activated (FVIIa) concentrations. Two randomized crossover trials in healthy male subjects compared the effects of meals containing 50 g fat [interesterified palm oil (IPO) versus native palm oil (NPO); n = 20, and IPO versus high-oleic sunflower oil (HOS); n = 18], on postprandial changes in lipids, glucose, insulin, chylomicron composition and FVIIa. Compared with NPO, IPO decreased postprandial TAG and insulin concentrations. Both NPO and IPO increased FVIIa concentrations postprandially; mean increases at 6 h were 21 and 19%, respectively. Compared with HOS, IPO decreased postprandial TAG (47% lower incremental area under the curve) and reduced the postprandial increase in FVIIa concentration by 64% at 6 h; no significant differences in hepatic and total lipase activities or insulin concentrations were noted. All three test meals increased postprandial leukocyte counts (average 26% at 6 h). The fatty acid composition of the chylomicron TAG was similar to the test fats following all test meals. It is concluded that interesterification of palm oil does not result in adverse changes in postprandial lipids, insulin or FVIIa compared to high oleate and native palm oils. George J. Miller: Deceased August 2006.     

Lipidomic Analysis of Serum from High Fat Diet Induced Obese Mice

Lipid metabolites regulate fatty acid and glucose homeostasis. The intention of the current study is to identify circulating lipid species, which are altered in rodent obesity and strongly correlate with the classically measured metabolites glucose, triglycerides, and cholesterol. Mice fed a high fat diet (HFD) for 14 weeks have increased body weight and fasting glucose. Serum triglycerides are not altered, while cholesterol tends to be increased. Accordingly, major cholesteryl ester (CE) species and free cholesterol are not significantly raised in obesity while minor metabolites, including CE 20:3 and CE 18:3, are increased or reduced, respectively. Distinct sphingomyelin (SM) species are elevated while ceramides are not raised. Phosphatidylinositol (PI) species, including PI 34:1, are raised while others are decreased. PI 34:1 strongly correlates with fasting glucose and proinsulin levels. Phosphatidylcholine (PC) 26:0, 40:2, and 40:5, which are induced in obesity, correlate with cholesterol. PC 38:4 and PC 40:6 are also raised in fat fed mice and positively correlate with fasting glucose. Lysophosphatidylcholine (LPC) species are also changed in obesity and the already shown reduction of LPC 16:1 has been confirmed. LPC 22:4, which is increased, correlates with serum cholesterol. The data indicate that circulating levels of various lipid species are changed in the obesity model studied and some of them are strongly associated with classically measured metabolites.     

Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet

We recently proposed that the biological markers improved by carbohydrate restriction were precisely those that define the metabolic syndrome (MetS), and that the common thread was regulation of insulin as a control element. We specifically tested the idea with a 12-week study comparing two hypocaloric diets (~1,500 kcal): a carbohydrate-restricted diet (CRD) (%carbohydrate:fat:protein = 12:59:28) and a low-fat diet (LFD) (56:24:20) in 40 subjects with atherogenic dyslipidemia. Both interventions led to improvements in several metabolic markers, but subjects following the CRD had consistently reduced glucose (−12%) and insulin (−50%) concentrations, insulin sensitivity (−55%), weight loss (−10%), decreased adiposity (−14%), and more favorable triacylglycerol (TAG) (−51%), HDL-C (13%) and total cholesterol/HDL-C ratio (−14%) responses. In addition to these markers for MetS, the CRD subjects showed more favorable responses to alternative indicators of cardiovascular risk: postprandial lipemia (−47%), the Apo B/Apo A-1 ratio (−16%), and LDL particle distribution. Despite a threefold higher intake of dietary saturated fat during the CRD, saturated fatty acids in TAG and cholesteryl ester were significantly decreased, as was palmitoleic acid (16:1n-7), an endogenous marker of lipogenesis, compared to subjects consuming the LFD. Serum retinol binding protein 4 has been linked to insulin-resistant states, and only the CRD decreased this marker (−20%). The findings provide support for unifying the disparate markers of MetS and for the proposed intimate connection with dietary carbohydrate. The results support the use of dietary carbohydrate restriction as an effective approach to improve features of MetS and cardiovascular risk. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Lipidomic Profiling Reveals the Effect of Egg Components on Nonalcoholic Steatosis in HepG2 Cells and Its Involved Mechanisms

Non‐alcoholic fatty liver disease (NAFLD) is a major cause of cardiovascular disease. The relationship between egg consumption and NAFLD is still controversial for its high cholesterol content. In this study, the effects of different egg components (egg white (EW), egg yolk (EY), and whole egg (WE)) on NAFLD are examined using oleic acid (OA)‐induced HepG2 cells with UPLC‐ESI‐MS/MS approach. The results show EY could affect the lipid profile effectively by increasing phosphocholine (PC), phosphatidylglycerol (PG), and carnitine (CAR). Orthogonal projections to latent structures?discriminate analysis (OPLS‐DA) combine with S‐plot analysis select 10, 82, and 20 potential biomarkers in EW, EY, and WE group, respectively. Up‐regulated TG, DG, and down‐regulated lysophosphatidylcholines (lysoPC), lysophosphatidylethanolamine (lysoPE) biomarkers are found in EY group, while down‐regulated TG and FFA are found in EW and WE group. Glycerolipid and choline metabolism are the most involved pathways affected by EY and WE. In addition, the mechanism is associated with the expression of Pla2g15, Pnpla6‐1, Gad1, and involved lipogenic genes ABC1 and PPARα. This study suggests that WE treatment can ameliorate OA‐induced hepatic steatosis by inhibiting TG accumulation, while EY seems slightly accelerate hepatic steatosis. Furthermore, the effects are closely associated with its effects on glycerolipid metabolism. Practical applications: Nonalcoholic fatty liver disease (NAFLD) is a worldwide disease, while the associations between egg consumption and NAFLD are still poorly understood. This study investigates the effects of egg components on NAFLD in oleic acid (OA)‐induced HepG2 cells based on a targeted lipidomics approach. The results indicate that WE (whole egg) treatment could ameliorate OA‐induced hepatic steatosis by inhibiting TG and FFA accumulation, which is closely associated with glycerolipid metabolism. The results provide knowledge and understanding of the effects of egg on NAFLD and involved mechanism, and further provided nutritional guidelines for egg consumption.     

Fatty Acid de Novo Synthesis in Adult Intrauterine Growth-Restricted Offspring,and Adult Male Response to a High Fat Diet

Intrauterine growth restriction (IUGR) with rapid catch‐up growth leads to adult obesity and insulin resistance. We have previously shown that IUGR male rats demonstrated increased de novo fatty acid synthesis in the subcutaneous (SC) fat, but not the visceral fat, during the nursing period prior to the onset of obesity. Young IUGR females do not exhibit the same increase. We further hypothesized that in male IUGR offspring, de novo synthesis is a programmed intrinsic effect that persists to adulthood and does not suppress in response to a high fat diet. We measured fatty acid de novo synthesis in IUGR adult males (6 months) using deuterium‐enriched drinking water as a stable isotope tracer, then further studied the response after consumption of an isocaloric high fat diet. Baseline de novo synthesis in adult females was also studied at age 9 months. Males demonstrated increased baseline de novo synthesis in both SC fat and visceral fat. Correspondingly, SC and visceral fat protein expression of lipogenic enzymes acetyl‐coA carboxylase‐α (ACCα) and fatty acid synthase were upregulated. After the isocaloric high fat diet, de novo synthesis was suppressed such that no differences remained between the two groups, although, IUGR SC fat demonstrated persistently increased lipogenic protein expression. In contrast, de novo synthesis among adult females is not impacted in IUGR. In conclusion, enhancement of male IUGR SC fat de novo synthesis appears to be an early consequence of metabolic programming, whereas enhancement in visceral fat appears to be a later consequence.     

Lipidomic Study of Precursors of Endocannabinoids in Freshwater Bryozoan Pectinatella magnifica

Freshwater bryozoan Pectinatella magnifica was collected from a sand pit (South Bohemia). The total lipids after extraction from lyophilized bryozoans were analyzed using high‐performance liquid chromatography/high‐resolution negative tandem electrospray mass spectrometry. A total of 19 lipid classes were identified, including N‐acyl‐substituted phospholipids, that is, N‐acylphosphatidylethanolamine and N‐acylphosphatidylserine in their plasmenyl forms. Based on gas chromatography/mass spectrometry of 3‐pyridylcarbonyl (picolinyl) esters, a very unusual fatty acid was identified, namely 24:7n‐3 (all‐cis‐3,6,9,12,15,18,21‐tetracosaheptaenoic acid). The presence of polyunsaturated fatty acids in individual classes is very specific: arachidonic and eicosapentaenoic acids being predominantly bound as amides in N‐acyl phospholipids, that is, diacyl‐N‐acylphosphatidylethanolamines (NAPtdEtn), plasmenyl‐N‐acylphosphatidyl ethanolamines (PlsNAPtdEtn), diacyl‐N‐acylphosphatidylserines (NAPtdSer), and plasmenyl‐N‐acylphosphatidylserines (PlsNAPtdSer). While 24:6n‐3 was identified in the sn‐2 position of several phospholipids, 24:7n‐3 was identified in only two plasmalogens, that is, PlsNAPtdEtn and PlsNAPtdSer. Thanks to the tandem mass spectrometry, we managed to identify the position of all acyl groups in both diacyl‐ and also in alkenyl‐acyl‐(plasmenyl) molecular species of N‐acylphospholipids. The identification of the molecular species of N‐acyl‐substituted phosphatidylethanolamine and phosphatidylserine, including their plasmalogen forms, in the freshwater bryozoan P. magnifica has enabled the identification of endogenous cannabinoid precursors.     

Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease with progressive central nervous system involvement. This study examined the lipid, cholesterol, and myelin basic protein composition of white matter in the corpus callosum of MPS I mice. We studied 50 week-old, male MPS I mice and littermate, heterozygote controls (n = 12 per group). Male MPS I mice showed lower phosphatidylcholine and ether-linked phosphatidylcholine quantities than controls (p < 0.05). Twenty-two phospholipid or ceramide species showed significant differences in percent of total. Regarding specific lipid species, MPS I mice exhibited lower quantities of sphingomyelin 18:1, phosphatidylserine 38:3, and hexosylceramide d18:1(22:1) mH₂O than controls. Principal components analyses of polar, ceramide, and hexosylceramide lipids, respectively, showed some separation of MPS I and control mice. We found no significant differences in myelin gene expression, myelin basic protein, or total cholesterol in the MPS I mice versus heterozygous controls. There was a trend toward lower proteolipid protein-1 levels in MPS I mice (p = 0.06). MPS I mice show subtle changes in white matter composition, with an unknown impact on pathogenesis in this model.     

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.     

Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets

We previously demonstrated the marked hepatosteatosis and endothelial dysfunction in hepatocyte-specific ERK2 knockout mice (LE2KO) with a high-fat/high-sucrose diet (HFHSD), but detailed metabolic changes and the characteristics in insulin-sensitive organs were not tested. This study aimed to characterize metabolic remodeling with changes in insulin-sensitive organs, which could induce endothelial dysfunction in HFHSD-LE2KO. The serum glucose and fatty acid (FA) were modestly higher in HFHSD-LE2KO than HFHSD-Control. FA synthesis genes were up-regulated, which was associated with the decreased phosphorylation of AMPK and ACC, and with the up-regulation of SREBP-1 in the liver from HFHSD-LE2KO. In FA and amino acids fraction analysis, arachidonic acid/eicosapentaenoic acid ratio, L-ornithine/arginine ratio, asymmetric dimethylarginine and homocysteine levels were elevated in HFHSD-LE2KO. Insulin-induced phosphorylation of AKT was blunted in skeletal muscle. Serum leptin and IL-1β were elevated, and serum adiponectin was decreased with the enlargement of epididymal adipocytes. Finally, the enhanced superoxide levels in the aorta, which were blunted with CCCP, apocynin, and tempol, were observed in HFHSD-LE2KO. A pre-incubation of aortic rings with tempol improved endothelial dysfunction in HFHSD-LE2KO. HFHSD-LE2KO revealed an acceleration of FA synthesis in the liver leading to insulin resistance in skeletal muscle and the enlargement of visceral adipocytes. Global metabolic remodeling such as changes in arginine metabolism, ω3/ω6 ratio, and adipocytokines, could affect the vascular oxidative stress and endothelial dysfunction in HFHSD-LE2KO.     

Stanniocalcin 1 Enhances Carbon Flux from Glucose to Lipids in White Retroperitoneal Adipose Tissue in the Fed Rat

The present work assesses in vitro the role of human Stanniocalcin 1 (hSTC‐1) in glucose metabolism in white retroperitoneal adipose tissue (WRAT) from fed rat. In the fed state, hSTC1 increases the incorporation of ¹⁴C from glucose into lipids in the rat WRAT. The increase in lipogenesis capacity supports the hypothesis that the activity of the glycerol‐3‐phosphate‐generating pathway (glycolysis) from glucose is regulated by hSTC‐1. The effect of hSTC‐1 on de novo fatty acid synthesis and on glucose oxidation in WRAT is supported by an 85 % increase in ¹⁴CO₂ production from ¹⁴C‐glucose. The incubation of WRAT in the presence of hSTC‐1 maintained the ADP/ATP ratio close to the control group. The presence of hSTC‐1 in the incubation medium did not inhibit the lipolytic effect of epinephrine. In conclusion, hSTC‐1 is one of the hormonal factors that control glucose metabolism in WRAT in the fed state.     

Loss of Fat with Increased Adipose Triglyceride Lipase-Mediated Lipolysis in Adipose Tissue During Laying Stages in Quail

The goal of the current study was to investigate regulation of key genes involved in lipid metabolism in adipose and liver to relate lipolytic and lipogenic capacities with physiological changes at the pre-laying, onset of laying, and actively laying stages of quail. Followed by a 50 % increase from pre-laying to onset of laying, adipose to body weight ratio was significantly reduced by 60 % from the onset of laying to the actively laying stage (P < 0.05), mainly resulting from the significantly increased adipocyte size from the pre-laying stage to the onset of laying and reduction of adipocyte size from the onset of laying to the actively laying stage (P < 0.05). In the adipose tissue of actively laying quail, increased protein expression and phosphorylation of adipose triglyceride lipase (ATGL) together with an elevated mRNA expression of comparative gene identification-58, an activator of ATGL, contributes to increased lipolytic activity, as proved by increased amounts of plasma non-esterified fatty acid (P < 0.05). In addition, decreased mRNA expression of fatty acid transport protein in the actively laying quail could contribute to the adipocyte hypotrophy (P < 0.05). In the liver, relative mRNA expression of apo-very low density lipoprotein (VLDL)-II increased significantly from the pre-laying to actively laying stages (P < 0.05), indicating increased apoVLDL-II actively facilitated VLDL secretion in the actively laying quail. These results suggest that the laying birds undergo active lipolysis in the adipocyte, and increase VLDL secretion from the liver in order to secure a lipid supply for yolk maturation.     

Inhibition of Serum Cholesterol Oxidation by Dietary Vitamin C and Selenium Intake in High Fat Fed Rats

Cholesterol oxidation products (COPs) have been considered as specific in vivo markers of oxidative stress. In this study, an increased oxidative status was induced in Wistar rats by feeding them a high-fat diet (cafeteria diet). Another group of animals received the same diet supplemented with a combination of two different antioxidants, ascorbic acid (100 mg/kg rat/day) and sodium selenite (200 μg/kg rat/day) and a third group fed on a control diet. Total and individual COPs analysis of the different diets showed no differences among them. At the end of the experimental trial, rats were sacrificed and serum cholesterol, triglycerides and COPs were measured. None of the diets induced changes in rats body weight, total cholesterol and triglycerides levels. Serum total COPs in rats fed on the high-fat diet were 1.01 μg/ml, two times the amount of the control rats (0.47 μg/ml). When dietary antioxidant supplementation was given, serum total COPs concentration (0.44 μg/ml) showed the same levels than those of the rats on control diet. 7β-hydroxycholesterol, formed non-enzymatically via cholesterol peroxidation in the presence of reactive oxygen species, showed slightly lower values in the antioxidant-supplemented animals compared to the control ones. This study confirms the importance of dietary antioxidants as protective factors against the formation of oxysterols.     

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.     

Effect of Dietary Cholesterol and Fat on Cell Cholesterol Transfer to Postprandial Plasma in Hyperlipidemic Men

Postprandial chylomicrons are potent ultimate acceptors of cell membrane cholesterol and are believed to accelerate reverse cholesterol transport (RCT). We compared the effects of meals rich in polyunsaturated fat (PUFA) and either high (605 mg) or low (151 mg) in cholesterol and a meal rich in dairy fat (DF) in the form of cream on net in vitro transport of red blood cell (RBC) membrane cholesterol to 4 and 6 h postprandial plasma in eight normotriglyceridemic (NTG-H) and eight hypertriglyceridemic (HTG-H) men with mild to moderate hypercholesterolemia. In HTG-H men, cell cholesterol accumulation in 6-h postprandial plasma was significantly (P = 0.02) less after the PUFA-HC meal compared with the other meals. The significant (P < 0.001) increase in cell plus endogenous cholesterol accumulation in the triglyceride-rich lipoprotein (TRL) fraction of 4 h postprandial plasma incubated with RBC was significantly (P = 0.007) higher after the PUFA-HC meal compared with DF meal in HTG-H men. In NTG-H men, cholesterol accumulation in plasma and plasma lipoproteins in the presence and absence of RBC was not significantly affected by the type of meal ingested. These data suggest that addition of large amounts of cholesterol to a PUFA meal may impair diffusion-mediated transport of cell membrane cholesterol to postprandial plasma and that replacing DF with PUFA in a meal increases postprandial lipemia and may potentially increase cholesterol accumulation in atherogenic postprandial TRL in HTG-H men.     

Lipid Metabolic Dose Response to Dietary Alpha-Linolenic Acid in Monk Parrot (Myiopsitta monachus)

Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258–266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.     

Metabolic Regulation and Lipidomic Remodeling in Relation to Spermidine-induced Stress Tolerance to High Temperature in Plants

Beneficial effects of spermidine (Spd) on alleviating abiotic stress damage have been explored in plants for hundreds of years, but limited information is available about its roles in regulating lipids signaling and metabolism during heat stress. White clover (Trifolium repens) plants were pretreated with 70 μM Spd and then subjected to high temperature (38/33 °C) stress for 20 days. To further investigate the effect of Spd on heat tolerance, transgenic Arabidopsis thaliana overexpressing a TrSAMS encoding a key enzyme involved in Spd biosynthesis was exposed to high temperature (38/33 °C) stress for 10 days. A significant increase in endogenous Spd content in white clover by exogenous application of Spd or the TrSAMS overexpression in Arabidopsis thaliana could effectively mitigate heat-induced growth retardation, oxidative damage to lipids, and declines in photochemical efficiency and cell membrane stability. Based on the analysis of metabolomics, the amino acids and vitamins metabolism, biosynthesis of secondary metabolites, and lipids metabolism were main metabolic pathways regulated by the Spd in cool-season white clover under heat stress. Further analysis of lipidomics found the TrSAMS-transgenic plants maintained relatively higher accumulations of total lipids, eight phospholipids (PC, phosphatidylcholine; PG, phosphatidylglycerol; PS, phosphatidylserine; CL, cardiolipin; LPA, lysophosphatidic acid; LPC, lyso phosphatidylcholine; LPG, lyso phosphatidylglycerol; and LPI, lyso phosphatidylinositol), one glycoglycerolipid (DGDG, digalactosyl diacylglycerol), and four sphingolipids (Cer, ceramide; CerG2GNAc1, dihexosyl N-acetylhexosyl ceramide; Hex1Cer, hexosyl ceramide; and ST, sulfatide), higher ratio of DGDG: monogalactosyl diacylglycerol (MGDG), and lower unsaturation level than wild-type Arabidopsis thaliana in response to heat stress. Spd-induced lipids accumulation and remodeling could contribute to better maintenance of membrane stability, integrity, and functionality when plants underwent a long period of heat stress. In addition, the Spd significantly up-regulated PIP2 and PA signaling pathways, which was beneficial to signal perception and transduction for stress defense. Current findings provide a novel insight into the function of Spd against heat stress through regulating lipids signaling and reprograming in plants.