Various Aspects Of Lipid Metabolism Research Articles

ANGPTL4-the Link Binding Lipid Metabolism and Inflammation.

Angiopoietin-like 4 (ANGPTL4) belongs to the family of angiopoietin- like proteins. The involvement of ANGPTL4 in various aspects of lipid metabolism and inflammation has become an important area of research. A thorough search on PubMed related to ANGPTL4, lipid metabolism, and inflammation was performed. Over the past two decades, the recognition of ANGPTL4 as a potent regulator of lipid metabolism has substantially increased. As part of the senescence-associated secretory phenotype, ANGPTL4 also serves as an inflammatory mediator. Considering the advancements in ANGPTL4 research, we have highlighted that ANGPTL4 acts as a key node linking lipid metabolism and inflammation. ANGPTL4 impacts inflammation by regulating lipid metabolism. It affects critical enzymes (lipoprotein lipase, hepatic lipase, endothelial lipase, and acetyl-CoA carboxylase), regulatory factors (AMPK, cAMP, SLC7A11, GPX4, and mTOR), and receptors (LepR, CD36, and PPARγ) of lipid oxidation, synthesis, and peroxidation, thereby affecting immune cells and inflammatory pathways. Understanding the potential association and the therapeutic value of ANGPTL4 for regulating lipid metabolism and inflammation could contribute to drug discovery and therapeutic development.

George Alan Garton. 4 June 1922—13 May 2010

Alan Garton and his group at The Rowett Research Institute in Aberdeen made very significant and unique contributions to the understanding of differences in digestion, absorption and metabolism of dietary lipids (fats) and their importance to health in mammalian species, particularly farm animals, but also various aspects of lipid metabolism and health in humans. The group were the first to use commercially available gas chromatography and first, this side of the Atlantic, to employ thin-layer chromatography for lipid analyses. A special adaptation of radio-gas chromatography, developed in-house, also led to the definitive evidence that radio-labelled methylmalonyl-CoA, derived from propionic acid, particularly from grain-fed sheep, can be utilized for fatty acid synthesis. Alan always highlighted the relevance of the group's lipid research to human health and wellbeing, as seen by the role of branched-chain fatty acids in Refsum's disease and the later development of studies of the role of saturated and essential omega-3, -6 and -9 fatty acids, including conjugated linoleic acids and trans fatty acids, in human health and disease by the group.

The Impact of Incretin-Based Medications on Lipid Metabolism.

Pathophysiological pathways that are induced by chronic hyperglycemia negatively impact lipid metabolism. Thus, diabetes is commonly accompanied by varying degrees of dyslipidemia which is itself a major risk factor for further macro- and microvascular diabetes complications such as atherosclerosis and nephropathy. Therefore, normalizing lipid metabolism is an attractive goal for therapy in patients with diabetes. Incretin-based medications are a novel group of antidiabetic agents with potent hypoglycemic effects. While the impact of incretins on glucose metabolism is clear, recent evidence indicates their positive modulatory roles on various aspects of lipid metabolism. Therefore, incretins may offer additional beneficial effects beyond that of glucose normalization. In the current review, how these antidiabetic medications can regulate lipid homeostasis and the possible cellular pathways involved are discussed, incorporating related clinical evidence about incretin effects on lipid homeostasis.

Using 14C-acetate Pulse-chase Labeling to Study Fatty Acid and Glycerolipid Metabolism in Plant Leaves.

Lipids metabolism is comprised of networks of reactions occurred in different subcellular compartments. Isotopic labeling is a good way to track the transformations and movements of metabolites without perturbing overall cellular metabolism. Fatty acids, the building blocks of membrane lipids and storage triacylglycerols, are synthesized in plastids. The immediate precursor for fatty acid synthesis is acetyl-CoA. Exogenous acetate is rapidly incorporated into fatty acids in leaves and isolated plastids because it can diffuse freely through cellular membranes, enter the plastid where it is rapidly metabolized to acetyl-CoA. Therefore, isotope-labeled acetate is often used as a tracer for the investigation of fatty acid synthesis and complex lipid metabolism in plants and other organisms. The basic principle of isotope labeling and its recent technological advances have been reviewed ( Allen et al., 2015 ). The present protocol describes the use of 14C-labeled acetate to determine rates of fatty acid synthesis and degradation and to track the metabolism of glycerolipids in leaves. This method, which is often referred to as acetate pulse-chase labeling, has been widely used to probe various aspects of lipid metabolism ( Allen et al., 2015 ), including the role of autophagy in membrane lipid turnover ( Fan et al., 2019 ) and the interplay between lipid and starch metabolism pathways ( Yu et al., 2018 ).

Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells.

The Roles of mTOR Complexes in Lipid Metabolism.

The synthesis of lipids in response to food intake represents a key advantage that allows organisms to survive when energy availability is limited. In mammals, circulating levels of insulin and nutrients, which fluctuate between fasting and feeding, dictate whether lipids are synthesized or catabolized by tissues. The mechanistic target of rapamycin (mTOR), a kinase that is activated by anabolic signals, plays fundamental roles in regulating lipid biosynthesis and metabolism in response to nutrition. The mTOR kinase nucleates two large protein complexes named mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Following their activation, these complexes facilitate the accumulation of triglycerides by promoting adipogenesis and lipogenesis and by shutting down catabolic processes such as lipolysis and β-oxidation. Here, we review and discuss the roles of mTOR complexes in various aspects of lipid metabolism in mammals. We also use this opportunity to discuss the implication of these relations to the maintenance of systemic lipid homeostasis.

Abstract 164: Identification of Genetic Regulators of the Atherosclerosis-Associated Metabolite Trimethylamine-N-Oxide in the Diversity Outbred Mice Population

Dietary choline and its derivatives have been associated with various aspects of lipid metabolism. Recently, the choline metabolite trimethylamine-N-oxide (TMAO) has been associated with atherosclerosis in both mice and humans. Traditional studies of atherosclerosis in mice use genetic or dietary manipulation to induce atherosclerosis in inbred mouse strains. However, traditional quantitative trait locus (QTL) mapping studies using inbred strains often identify large genomic regions, containing many genes, due to limited recombination and/or sample size which hamper candidate gene identification and translation of these results into possible risk factors and therapeutic targets. As an alternative approach, here we use the multi-parental Diversity Outbred (DO) mouse panel for genetic mapping in order to aid in the identification of causal genes and variants associated with TMAO and its precursor choline. We fed DO mice either a high-fat, cholesterol-containing (HFCA) diet or a low-fat, high-protein diet for 18 weeks and measured circulating metabolites at baseline and after diet. Among our highly significant loci, we detected a 4.6 Mb QTL interval on Chromosome 12 (LOD = 10.0, p<0.05) associated with plasma concentrations of the metabolite trimethylamine-N-oxide at baseline, containing 116 genes; the same QTL was also identified after dietary treatment (LOD= 6.7, p<0.1). By using a database of mouse gene expression and measuring gene expression in the eight progenitor strains by RNA-Sequencing, we identified three potential candidate genes, including the positional candidate gene Numb, which encodes a clathrin adapter with a role in endocytosis that was recently shown to modulate intestinal cholesterol absorption. We show that TMAO and Numb exhibit inverse strain variation across the DO founder strains and that the novel Chromosome 12 TMAO locus co-localizes with a highly significant cis-expression QTL for Numb, indicating a potential functional relationship.

Transcriptomic signatures of peroxisome proliferator-activated receptor α (PPARα) in different mouse liver models identify novel aspects of its biology.

BackgroundThe peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that regulates lipid catabolism and inflammation and is hepatocarcinogenic in rodents. It is presumed that the functions of PPARα in liver depend on cross-talk between parenchymal (hepatocytes) and non-parenchymal (Kupffer and endothelial cells) fractions as well as inter-organ interactions. In order to determine how cellular composition and inter-organ interactions influence gene expression upon pharmacological activation of PPARα, we performed a meta-analysis of transcriptomics data obtained from mouse hepatocytes (containing only the parenchymal fraction), mouse liver slices (containing both fractions), and mouse livers exposed to a PPARα agonist. The aim was to obtain a comprehensive view of common and model-specific PPARα-dependent genes and biological processes to understand the impact of cross-talk between parenchymal and non-parenchymal fractions as well as the effect of inter-organ interactions on the hepatic PPARα transcriptome.To this end we analyzed microarray data of experiments performed in mouse primary hepatocytes treated with the PPARα agonist Wy14643 for 6 or 24 h (in vitro), mouse precision cut liver slices treated with Wy14643 for 24 h (ex vivo), and livers of wild type and Ppara knockout mice treated with Wy14643 for 6 h or 5 days (in vivo).ResultsIn all models, activation of PPARα significantly altered processes related to various aspects of lipid metabolism. In ex vivo and in vivo models, PPARα activation significantly regulated processes involved in inflammation; these processes were unaffected in hepatocytes. Only in vivo models showed significant regulation of genes involved in coagulation, carcinogenesis, as well as vesicular trafficking and extracellular matrix.ConclusionsPPARα-dependent regulation of genes/processes involved in lipid metabolism is mostly independent of the presence of non-parenchymal cells or systemic factors, as it was observed in all liver models. PPARα-dependent regulation of inflammatory genes requires the presence of non-parenchymal cells, as it was observed only ex vivo and in vivo. However, the full spectrum of PPARα biology at the level of lipid metabolism, immunity, carcinogenesis, as well as novel aspects of PPARα signaling such as coagulation, vesicular trafficking and the extracellular matrix, seems to require systemic factors, as it was observed exclusively in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1106) contains supplementary material, which is available to authorized users.

Growth hormone enhances arachidonic acid metabolites in a growth hormone transgenic mouse.

In a transgenic growth hormone (GH) mouse model, highly elevated GH increases overall growth and decreases adipose depots while low or moderate circulating GH enhances adipose deposition with differential effects on body growth. Using this model, the effects of low, moderate, and high chronic GH on fatty acid composition were determined for adipose and hepatic tissue and the metabolites of 20:4n-6 (arachidonic acid) were characterized to identify metabolic targets of action of elevated GH. The products of Δ-9 desaturase in hepatic, but not adipose, tissue were reduced in response to elevated GH. Proportional to the level of circulating GH, the products of Δ-5 and Δ-6 were increased in both adipose and hepatic tissue for the omega-6 lipids (e.g., 20:4n-6), while only the hepatic tissues showed an increase for omega-3 lipids (e.g., 22:6n-3). The eicosanoids, PGE₂ and 12-HETE, were elevated with high GH but circulating thromboxane was not. Hepatic PTGS1 and 2 (COX1 and COX 2), SOD1, and FADS2 (Δ-6 desaturase) mRNAs were increased with elevated GH while FAS mRNA was reduced; SCD1 (stearoyl-coenzyme A desaturase) and SCD2 mRNA did not significantly differ. The present study showed that GH influences the net flux through various aspects of lipid metabolism and especially the desaturase metabolic processes. The combination of altered metabolism and tissue specificity suggest that the regulation of membrane composition and its effects on signaling pathways, including the production and actions of eicosanoids, can be mediated by the GH regulatory axis.

Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

Peroxisome proliferator-activated receptor delta (PPARdelta) is involved in regulation of energy homeostasis. Activation of PPARdelta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary cholesterol secretion, nor by reduced cholesterol absorption. To test the hypothesis that PPARdelta activation leads to stimulation of transintestinal cholesterol efflux (TICE), we quantified it by intestine perfusions in FVB mice treated with PPARdelta agonist GW610742. To exclude the effects on cholesterol absorption, mice were also treated with cholesterol absorption inhibitor ezetimibe or ezetimibe/GW610742. GW601742 treatment had little effect on plasma lipid levels but stimulated both fecal neutral sterol excretion ( approximately 200%) and TICE ( approximately 100%). GW610742 decreased intestinal Npc1l1 expression but had no effect on Abcg5/Abcg8. Interestingly, expression of Rab9 and LIMPII, encoding proteins involved in intracellular cholesterol trafficking, was increased upon PPARdelta activation. Although treatment with ezetimibe alone had no effect on TICE, it reduced the effect of GW610742 on TICE. These data show that activation of PPARdelta stimulates fecal cholesterol excretion in mice, primarily by the two-fold increase in TICE, indicating that this pathway provides an interesting target for the development of drugs aiming at the prevention of atherosclerosis.

Lipid Metabolism in the Liver

As a key metabolic organ, the liver is central to the imbalance of high-caloric diets, and particularly dietary fat consumption, in the industrialized countries and their association with the increasing prevalence of morbid obesity. By interacting with the intestinal tract and adipose tissue, the liver plays a key role in various aspects of lipid metabolism. Increasing activation of transcription factors, such as carbohydrate responsive element binding protein (ChREBP), sterol response element binding protein-1c (SREBP-1c), or forkhead box 01 (Fox01), may contribute to fatty acid synthesis. Their translocation occurs via fatty acid transporters such as fatty acid transport proteins (FATP), fatty acid translocase (FAT/CD36), caveolin-1 and fatty acid binding protein (FABP) . Eventually, the accumulation of fat in the form of lipid droplets within the hepatocytes results in hepatic steatosis which, indeed, is a hallmark of liver diseases such as non-alcoholic fatty liver disease, alcoholic fatty liver, acute fatty liver in pregnancy, and hepatitis C. In contrast, lipid accumulation within hepatocytes during liver regeneration is essential. It is thus now becoming clear that steatosis is not only a mere consequence of metabolic imbalance, but that it is also a result of discrete alterations in the beta-oxidation, transport mechanisms, and signaling pathways involved in the synthesis, systemic traffic modalities, and cellular effects of fatty acids. Such a novel insight offers potential options for improved treatment.

Alteration of Adipocyte Metabolism in ω3 Fatty Acid-depleted Rats

Presently an insufficient supply of long-chain polyunsaturated omega3 fatty acid is prevalent in Western populations leading to potential metabolic consequences. Based on this fact, this study deals mainly with various aspects of lipid metabolism in second generation female omega3-depleted rats. The parametrial fat and body weights were higher in omega3-depleted than control animals. This coincided with liver steatosis but did not alter heart triglyceride/phospholipid ratio. The net uptake of [U-14C] palmitate by adipocytes was also higher in omega3-depleted rats than in control animals. The uptake of D-[U- 4C] glucose or [1,2 (-14)C] acetate by adipocytes was lower, however in omega3-depleted than control animals and was unaffected by insulin in the former as distinct from latter animals. Despite comparable basal lipolysis, the increase in glycerol output from adipocytes provoked by theophylline was higher in omega3-depleted than control rats. The fatty acid pattern of lipids in adipose tissue was characterized in the omega3-depleted rats by a much lower omega3 content, higher apparent Delta 9-saturase and elongase activities, lower efficiency for the conversion of C18:2omega6 to C20:4omega6 and higher efficiency for the conversion of C18:3omega3 to C20:5omega3. These features were compared to those prevailing in liver and plasma lipids. The present study thus extends knowledge on the alteration of lipid metabolism resulting from a deficiency in long-chain polyunsaturated omega3 fatty acids.

A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPARα-dependent and -independent pathways

Branched-chain fatty acids (such as phytanic and pristanic acid) are ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro. To investigate the effects of these physiological compounds in vivo, wild-type and PPARalpha-deficient (PPARalpha-/-) mice were fed a phytol-enriched diet. This resulted in increased plasma and liver levels of the phytol metabolites phytanic and pristanic acid. In wild-type mice, plasma fatty acid levels decreased after phytol feeding, whereas in PPARalpha-/- mice, the already elevated fatty acid levels increased. In addition, PPARalpha-/- mice were found to be carnitine deficient in both plasma and liver. Dietary phytol increased liver free carnitine in wild-type animals but not in PPARalpha-/- mice. Investigation of carnitine biosynthesis revealed that PPARalpha is likely involved in the regulation of carnitine homeostasis. Furthermore, phytol feeding resulted in a PPARalpha-dependent induction of various peroxisomal and mitochondrial beta-oxidation enzymes. In addition, a PPARalpha-independent induction of catalase, phytanoyl-CoA hydroxylase, carnitine octanoyltransferase, peroxisomal 3-ketoacyl-CoA thiolase, and straight-chain acyl-CoA oxidase was observed. In conclusion, branched-chain fatty acids are physiologically relevant ligands of PPARalpha in mice. These findings are especially relevant for disorders in which branched-chain fatty acids accumulate, such as Refsum disease and peroxisome biogenesis disorders.

Fat metabolism during total parenteral nutrition: a biochemical and ultra‐structural study

Background: Before the introduction of Intralipid in 1961, the incidence of adverse reactions to intravenous fat emulsions was quite common. Concurrent with hyperlipidaemia, multiple organ dysfunction could occur, but the most prominent symptoms were high fever and anaemia, and the reaction was called “the fat overloading syndrome”. Although the reports are quite rare today the reaction does still appear, and we have observed that some patients develop severe fever during or after incidental retention of exogenous fat in the blood during total parenteral nutrition (TPN). The pathophysiological background to these adverse reactions, as well as the final destiny and the effects of the retained exogenous fat particles, are largely unknown. These questions initiated the present study, which focuses on two factors of importance for the clearance of infused fat from the circulation: the lipoprotein lipase (LPL) system and the reticluloendo‐thelial system.Methods: An introductory analysis of the clinical course of a head‐injured patient suffering from fat intolerance during TPN implied that observed adverse reactions could be due to influence on macrophages by retained exogenous fat particles.Results: During infusion of lipid emulsions, cholesterol and phospholipids accumulated in non‐high‐density lipoproteins, while high‐density lipoproteins were enriched in triglycerides. Triglycerides also accumulated in hepatic tissue, and the activity of hepatic lipase decreased.Although lipoprotein lipase activity in the heart was up‐regulated and serum levels of triglycerides were normal, suggesting that the total elimination rate of triglycerides was not impaired, ultra‐structural investigations indicated that Kupffer cells were involved in clearing exogenous lipids from the blood during the infusion of long‐chain triglycerides. Furthermore, the Kupffer cells were activated, according to morphological criteria. When high doses of fat were given intravenously, the Kupffer cells were grossly distended by fat vacuoles, and serum levels of lactate dehydrogenase increased.During treatment with fat emulsions containing medium‐chain triglycerides and long‐chain triglycerides in equal amounts, the alterations in lipid transport were less pronounced, and signs of Kupffer cell activation were weaker than during infusion with long‐chain triglycerides only.Conclusion: The experimental studies showed that infusion of exogenous fat particles interfered with the regulation of lipid transport, and there were signs of increased demands on various aspects of lipid metabolism. Although the capacity of the LPL was sufficient in most situations in healthy rats, the Kupffer cells seemed to be involved in the clearance of exogenous lipids. The present investigations identified one factor, LCT fat emulsion, which was necessary for the appearance of fat vacuoles in the Kupffer cells during TPN.To some extent, the experimental findings may be related to clinical observations of a head‐injured patient who developed signs of acute, severe macrophage activation with haemophago‐cytosis during and after accumulation of exogenous fat in the blood after treatment with intravenous fat emulsions. The condition was considered to be a consequence of impaired lipid elimination and altered macrophage function during clearance of fat from the blood, a consideration supported by the morphological changes of rat Kupffer cells after TPN in the present study.

Naturally occurring mutations in mice affecting lipid transport and metabolism.

Naturally occurring mutations in the mouse provide a unique resource for identifying genes and characterizing proteins involved in lipid metabolism. Spontaneous mouse mutations have been described that affect various aspects of lipid metabolism, including cellular cholesterol homeostasis, fatty acid metabolism, serum lipoprotein levels, serum and tissue lipase activities, and lipid composition of tissues such as liver, nerve, kidney, and adrenal gland. Here we briefly describe the phenotypes and genetics of several mutants with blood and tissue lipid abnormalities, and then provide a more in-depth discussion of two mutations, fatty liver dystrophy (fld) and combined lipase deficiency (cld). Mice homozygous for the fld mutation exhibit fatty liver and hypertriglyceridemia during neonatal development, and a peripheral neuropathy that progresses throughout the lifetime of the animal. Combined lipase deficiency is characterized by a nearly complete absence of lipoprotein lipase and hepatic lipase activity resulting in neonatal lethality. Although the underlying genes for these two disorders have yet to be identified, candidates that have been implicated through the molecular and biochemical characterization of the mutants are discussed.

In vitro model systems: cell cultures used in lipid and lipoprotein research

Cell cultures have been used extensively to study various aspects of lipid metabolism as they provide the simple but important model systems needed to understand various physiological and biochemical functions. Some of the characteristics of cultured cells and important contributions that have been derived from these cells in lipid and lipoprotein research are highlighted. In addition, the future use of cell cultures for various aspects of lipid metabolism is discussed.

Effects of different saturated fats on various aspects of lipid metabolism in rats hypersensitive to dietary cholesterol

Effects of palm oil (PO) and coconut oil (CO) mixed with corn on lipid metabolism were compared with those of lard in rats hypersensitive to dietary cholesterol. Rats were fed one of four cholesterol-enriched diets containing different dietary fats, equiweight mixtures of either soybean oil-lard or soybean oil-lard-PO-CO, at about 26 or 42 energy % levels. The concentration of serum cholesterol did not increase when polyunsaturated fat was replaced with saturated fat of plant origin, and it tended to be lower with an increase in the dietary fat level. In addition, the PO-CO mixture reduced the liver cholesterol concentration at both energy levels compared with lard. There was no fat-dependent difference in fecal steroid excretion and the fatty acid composition of serum and liver phospholipids. Zymosan injection caused a reduction of serum triglyceride in the PO-CO group and a reduction of liver cholesterol in the lard group. The elevation of serum cholesterol and the reduction of liver triglyceride upon injection of zymosan were independent of the source of dietary saturated fats. Thus, PO and CO in combination may specifically modulate lipid metabolism under the immunologically stimulated as well as non-stimulated situations.

Oxidant stress inhibits the endogenous production of lipoxygenease metabolites in rat lungs and fish gills

Hydroperoxides are potent initiators of lipid peroxidation in vivo. Acyl hydroperoxides may also regulate various aspects of lipid metabolism. In this study we investigated the regulation of the endogenous 12 lipoxygenase in trout gill and rat lung, a prominant acyl hydroperoxide catalyst in these tissues. Initial experiments revealed that the enzyme from trout gill was activated by hydroperoxides at low levels and inactivated by the same hydroperoxides at high levels. Homogenization of these tissues resulted in the production of a predominant metabolite class from released endogenous polyunsaturated fatty acids, the 12 lipoxygenase products. In rat lung, arachidonic acid was the major polyunsaturated fatty acid released and 12 (S) HETE was the major metabolite. In trout gill 20:4, 20:5 n3, and 22:6 n3 were released and the 12(S), 12, and 14 hydroxy derivatives the corresponding metabolites. Computer simulations of the sensitivity of these enzymes to hydroperoxides predicted that exogenous oxidant stress would reduce significantly the production of HETEs. Tertiary butyl hydroperoxide was added to tissue homogenates and resulted in elimination of >95% of the lipoxygenase activity. These results suggest that the lipoxygenase enzyme in lung and gill tissue is a major potential source for acyl hydroperoxides in vivo, but is also very sensitive to oxidant including the acyl hydroperoxides themselves. This enzyme could thus be an important focus for oxidant injury in lungs.

Accumulation of (n-9)-eicosatrienoic and docosatrienoic acids in human fibroblast phospholipids.

An essential fatty acid (EFA) deficiency-like profile of fatty acids has been observed in HF-1 human skin fibroblasts cultured at clonal densities in MCDB 110 and 0.4% fetal bovine serum (FBS). The profile was characterized by an accumulation of 16:1n-7, 18:1n-9, 20:3n-9 and 22:3n-9, a reduction of n-6 fatty acids and a reduction in total polyunsaturated fatty acids (PUFA). The fatty acid composition of sphingomyelin (SPH), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) was determined and, except for SPH, each displayed an EFA deficiency-like profile. The triene to tetraene ratio (20:3n-9/20:4n-6) ranged from 5.3 in PI to 0.9 in PE. In addition, the highest percentage of 20:3n-9 was present in the PI and the highest percentage of 22:3n-9, in PE. Other human fibroblasts (normal, transformed and at different population doubling number levels [PDL]) were grown under the same conditions and were found to display triene to tetraene ratios (20:3n-9/20:4n-6) in total cellular lipids ranging from 0.7 to 4.5. The accumulation of 20:3n-9 and 22:3n-9 is due primarily to the existence of a basal nutrient medium (MCDB 110) that allows for the rapid clonal growth of human fibroblasts at reduced serum levels (0.4%). This culture procedure can be exploited to further elucidate various aspects of lipid metabolism in human fibroblasts.

The effect of feeding Di-(2-ethylhexyl) phthalate (DEHP) on the lipid metabolism of laying hens.

AbstractDi‐(2‐ethylhexyl)phthalate (DEHP), a commonly used plasticizer, is now seen as an environmental pollutant. DEHP has been found to inhibit lipid and sterol synthesis in rats and mice. The effects of DEHP on various aspects of lipid metabolism were examined in chickens. White Leghorn laying hens were fed either a standard laying mash control diet (C) or the control diet containing 1% DEHP (DEHP) or 1% DEHP and 5% tallow (DEHP‐T) for 28 days. DEHP and DEHP‐T lowered feed consumption 10% but did not significantly affect body weight. After 3 weeks on the diets, egg production was 15–20% less in DEHP‐T than in C and DEHP hens. No differences were observed in egg weight, percent shell, white or yolk among the groups. DEHP and DEHP‐T did not alter egg lipid or egg cholesterol concentrations. DEHP and DEHP‐T lowered plasma lipid concentration about 20% and free and total cholesterol 20–30%. Liver weights increased, being 30, 34 and 39 g for C, DEHP and DEHP‐T hens, respectively, after 28 days. Total liver lipid and cholesterol increased 19% and 26% in DEHP hens and 54% and 79% in DEHP‐T hens when compared to controls. In contrast, the fat content of pectoralis major muscle decreased significantly in DEHP and DEHP‐T hens. These results, in showing that DEHP alters plasma and tissue cholesterol but not yolk cholesterol, demonstrate again that egg cholesterol is remarkably resistant to alteration by dietary means.