Progress in Lipid Research

Published by Elsevier
Online ISSN: 0163-7827
Publications
Article
In this review we have tried to present the current thinking on the consequences for lipids of their interactions with free radicals and the pathological implications. In particular, atherosclerosis and cancer have been addressed. In the case of the former, it is not clear whether the initial oxidative event is an enzymic or free radical-mediated process as yet. However, the importance of the antioxidants in controlling LDL oxidation, macrophage uptake of oxidatively modified LDL and progression of atheroma in animal models certainly suggests an important propagative role for free radical-mediated events. With regard to cancer, oxidative modification of cell lipids has potential consequences for tumour cell proliferation. Whilst lipid hydroperoxides can serve as an origin of prostaglandins with tumour inhibitor (or immunosuppressive) properties, they may also influence cellular growth regulatory proteins normally dependent on membrane lipid integrity. Alternatively, they may function as a source of aldehydic breakdown products capable of 'down-regulating' cell proliferation through covalent modification of regulatory proteins. Oils rich in n-3 polyunsaturated fatty acids have toxic effects towards tumour cells. This toxicity is not mediated by prostaglandins but rather through the capacity of such agents to elevate the levels of lipid peroxides. This may be enhanced by active oxygen species released constitutively from tumour cells.
 
Article
Phosphatidylcholine (PC) is the major membrane-forming phospholipid in eukaryotes and can be synthesized by either of two pathways, the methylation pathway or the CDP-choline pathway. Many prokaryotes lack PC, but it can be found in significant amounts in membranes of rather diverse bacteria and based on genomic data, we estimate that more than 10% of all bacteria possess PC. Enzymatic methylation of phosphatidylethanolamine via the methylation pathway was thought to be the only biosynthetic pathway to yield PC in bacteria. However, a choline-dependent pathway for PC biosynthesis has been discovered in Sinorhizobium meliloti. In this pathway, PC synthase, condenses choline directly with CDP-diacylglyceride to form PC in one step. A number of symbiotic (Rhizobium leguminosarum, Mesorhizobium loti) and pathogenic (Agrobacterium tumefaciens, Brucella melitensis, Pseudomonas aeruginosa, Borrelia burgdorferi and Legionella pneumophila) bacteria seem to possess the PC synthase pathway and we suggest that the respective eukaryotic host functions as the provider of choline for this pathway. Pathogens entering their hosts through epithelia (Streptococcus pneumoniae, Haemophilus influenzae) require phosphocholine substitutions on their cell surface components that are biosynthetically also derived from choline supplied by the host. However, the incorporation of choline in these latter cases proceeds via choline phosphate and CDP-choline as intermediates. The occurrence of two intermediates in prokaryotes usually found as intermediates in the eukaryotic CDP-choline pathway for PC biosynthesis raises the question whether some bacteria might form PC via a CDP-choline pathway.
 
Article
Since the pathways of glycerolipid biosynthesis were elucidated in the 1950's, considerable knowledge has been gained about the enzymes that catalyze the lipid biosynthetic reactions and the factors that regulate triacylglycerol biosynthesis. In the last few decades, in part due to advances in technology and the wide availability of nucleotide and amino acid sequences, we have made enormous strides in our understanding of these enzymes at the molecular level. In many cases, sequence information obtained from lipid biosynthetic enzymes of prokaryotes and yeast has provided the means to search the genomic and expressed sequence tag databases for mammalian homologs and most of the genes have now been identified. Surprisingly, multiple isoforms appear to catalyze the same chemical reactions, suggesting that each isoform may play a distinct functional role in the pathway of triacylglycerol and phospholipid biosynthesis. This review focuses on the de novo biosynthesis of triacylglycerol in eukaryotic cells, the isoenzymes that are involved, their subcellular locations, how they are regulated, and their putative individual roles in glycerolipid biosynthesis.
 
Article
Ruminants supply humans with a readily available source of fat in the form of both tissue and milk lipids. It has been known for over 50 years that the compositions of ruminant tissue and milk lipids differ markedly from those of non-ruminant herbivores (Banks and Hilditch, 1931), and much research has been done on ruminant lipids and on the microbial transformations in the rumen which are responsible for the distinctive lipid composition. Early reviews on lipid metabolism in the rumen are by Viviani (1970), in which there is much information on microbial lipid composition, and by Harfoot (1978), which takes a wider view. Much of the older work has been referred to in detail in these reviews. More general accounts are those of Hungate (1966), Prins (1977) and Hobson and Wallace (1982a, b). Since the first edition (1988) of the present book, two further reviews have been published; one by Jenkins (1993) on general lipid metabolism in the rumen, and a shorter review (Jenkins, 1994) dealing with factors regulating lipid metabolism.
 
Article
The quality of dietary fat in relation to cardiovascular disease forms the basis of the diet-heart hypothesis. Current recommendations on dietary fat now emphasise quality rather than quantity. The focus of this review is to summarise the results from prospective cohort studies on dietary fat and cardiovascular disease outcomes. Relatively few prospective cohort studies have found an association between dietary fat quality and cardiovascular disease, partly because of limitations in estimating dietary intake. Saturated and trans fatty acids have increased cardiovascular risk in several studies. Both n-6 and n-3 polyunsaturated fatty acids have been associated with lower cardiovascular risk. Within the n-6 series, linoleic acid seems to decrease cardiovascular risk. Within the n-3 series the long-chain fatty acids (eicosapentaenoic and docosahexaenoic acids) are associated with decreased risk for especially fatal coronary outcomes, whereas the role of alpha-linolenic acid is less clear. Dietary fat quality also influences the activity of enzymes involved in the desaturation of fatty acids in the body. Serum desaturase indices have been consistently associated with adverse cardiovascular outcomes. Data from metabolic and clinical studies reinforce findings from observational studies supporting recommendations to replace saturated and trans fat with unsaturated fat in the prevention of cardiovascular disease.
 
Article
The de novo synthesis of fatty acids in plants occurs in the plastids through the activity of fatty acid synthetase. The synthesis of the malonyl-coenzyme A that is required for acyl-chain elongation requires the import of metabolites from the cytosol and their subsequent metabolism. Early studies had implicated acetate as the carbon source for plastidial fatty acid synthesis but more recent experiments have provided data that argue against this. A range of cytosolic metabolites including glucose 6-phosphate, malate, phosphoenolpyruvate and pyruvate support high rates of fatty acid synthesis by isolated plastids, the relative utilisation of which depends upon the plant species and the organ from which the plastids are isolated. The import of these metabolites occurs via specific transporters on the plastid envelope and recent advances in the understanding of the role of these transporters are discussed. Chloroplasts are able to generate the reducing power and ATP required for fatty acid synthesis by capture of light energy in the reactions of photosynthetic electron transport. Regulation of chloroplast fatty acid synthesis is mediated by the response of acetyl-CoA carboxylase to the redox state of the plastid, which ensures that the carbon metabolism is linked to the energy status. The regulation of fatty acid synthesis in plastids of heterotrophic cells is much less well understood and is of particular interest in the tissues that accumulate large amounts of the storage oil, triacylglycerol. In these heterotrophic cells the plastids import ATP and oxidise imported carbon sources to produce the required reducing power. The sequencing of the genome of Arabidopsis thaliana has now enabled a number of aspects of plant fatty acid synthesis to be re-addressed, particularly those areas in which in vitro biochemical analysis had provided equivocal answers. Examples of such aspects and future opportunities for our understanding of plant fatty acid synthesis are presented and discussed.
 
Article
The importance of a high fat intake in the increasing prevalence of childhood and adult obesity remains controversial. Moreover, qualitative changes (i.e. the fatty acid composition of fats) have been largely disregarded. Herein is reviewed the role of polyunsaturated fatty acids (PUFAs) of the n-6 series in promoting adipogenesis in vitro and favouring adipose tissue development in rodents during the gestation/suckling period. Epidemiological data from infant studies as well as the assessment of the fatty acid composition of mature breast milk and infant formulas over the last decades in the Western industrialized world are revisited and appear consistent with animal data. Changes over decades in the intake of n-6 and n-3 PUFAs, with a striking increase in the linoleic acid/alpha-linolenic ratio, are observed. In adults, using a consumption model based upon production data, similar changes in the PUFA content of ingested lipids have been found for France, and are associated with an increase of fat consumption over the last 40 years. These profound quantitative and qualitative alterations can be traced in the food chain and shown to be due to changes in human dietary habits as well as in the feeding pattern of breeding stock. If prevention of obesity is a key issue for future generations, agricultural and food industry policies should be thoroughly reevaluated.
 
Article
This article summarizes the current knowledge available on metabolism and the biological effects of n-3 docosapentaenoic acid (DPA). n-3 DPA has not been extensively studied because of the limited availability of the pure compound. n-3 DPA is an elongated metabolite of EPA and is an intermediary product between EPA and DHA. The literature on n-3 DPA is limited, however the available data suggests it has beneficial health effects. In vitro n-3 DPA is retro-converted back to EPA, however it does not appear to be readily metabolised to DHA. In vivo studies have shown limited conversion of n-3 DPA to DHA, mainly in liver, but in addition retro-conversion to EPA is evident in a number of tissues. n-3 DPA can be metabolised by lipoxygenase, in platelets, to form ll-hydroxy-7,9,13,16,19- and 14-hydroxy-7,10,12,16,19-DPA. It has also been reported that n-3 DPA is effective (more so than EPA and DHA) in inhibition of aggregation in platelets obtained from rabbit blood. In addition, there is evidence that n-3 DPA possesses 10-fold greater endothelial cell migration ability than EPA, which is important in wound-healing processes. An in vivo study has reported that n-3 DPA reduces the fatty acid synthase and malic enzyme activity levels in n-3 DPA-supplemented mice and these effects were stronger than the EPA-supplemented mice. Another recent in vivo study has reported that n-3 DPA may have a role in attenuating age-related decrease in spatial learning and long-term potentiation. However, more research remains to be done to further investigate the biological effects of this n-3 VLCPUFA.
 
Article
Local airway inflammation in chronic respiratory disease is well described. Recently it has been recognised that chronic obstructive respiratory disease, asthma and obstructive sleep apnoea, all involve a systemic inflammatory component. Overspill of airway inflammation, as well as direct metabolic effects, are potential contributors to systemic inflammation. This review will discuss the role of certain types of fatty acids in promoting systemic inflammation, via the innate immune response. Fatty acids are necessary as the key energy source in the body. However, they can be detrimental if present in excess. Various features of respiratory disease lead to altered lipid metabolism, and notably an increase in circulating levels of non-esterified fatty acids (NEFA). Dietary intake, obesity, hypoxia and smoking, will be discussed as factors promoting an increase in circulating NEFA. While n-3 polyunsaturated and monounsaturated fatty acids may be non-(or anti-)inflammatory, saturated and n-6 polyunsaturated fatty acids have been shown to stimulate the innate immune response. Thus, increased circulating NEFA may be directly contributing to systemic inflammation, thereby increasing susceptibility of individuals to chronic inflammatory diseases, including respiratory disease, cardiovascular disease and diabetes. Finally, the review will discuss how the recognition of NEFA as important inflammatory stimulants in respiratory disease, leads to the possibility that pathways involved in lipid metabolism may provide therapeutic targets.
 
Article
Vitamin E is a fat-soluble vitamin. It is comprised of a family of hydrocarbon compounds characterised by a chromanol ring with a phytol side chain referred to as tocopherols and tocotrienols. Tocopherols possess a saturated phytol side chain whereas the side chain of tocotrienols have three unsaturated residues. Isomers of these compounds are distinguished by the number and arrangement of methyl substituents attached to the chromanol ring. The predominant isomer found in the body is alpha-tocopherol, which has three methyl groups in addition to the hydroxyl group attached to the benzene ring. The diet of animals is comprised of different proportions of tocopherol isomers and specific alpha-tocopherol-binding proteins are responsible for retention of this isomer in the cells and tissues of the body. Because of the lipophilic properties of the vitamin it partitions into lipid storage organelles and cell membranes. It is, therefore, widely distributed in throughout the body. Subcellular distribution of alpha-tocopherol is not uniform with lysosomes being particularly enriched in the vitamin compared to other subcellular membranes. Vitamin E is believed to be involved in a variety of physiological and biochemical functions. The molecular mechanism of these functions is believed to be mediated by either the antioxidant action of the vitamin or by its action as a membrane stabiliser. alpha-Tocopherol is an efficient scavenger of lipid peroxyl radicals and, hence, it is able to break peroxyl chain propagation reactions. The unpaired electron of the tocopheroxyl radical thus formed tends to be delocalised rendering the radical more stable. The radical form may be converted back to alpha-tocopherol in redox cycle reactions involving coenzyme Q. The regeneration of alpha-tocopherol from its tocopheroxyloxyl radical greatly enhances the turnover efficiency of alpha-tocopherol in its role as a lipid antioxidant. Vitamin E forms complexes with the lysophospholipids and free fatty acids liberated by the action of membrane lipid hydrolysis. Both these products form 1:1 stoichiometric complexes with vitamin E and as a consequence the overall balance of hydrophobic:hydrophillic affinity within the membrane is restored. In this way, vitamin E is thought to negate the detergent-like properties of the hydrolytic products that would otherwise disrupt membrane stability. The location and arrangement of vitamin E in biological membranes is presently unknown. There is, however, a considerable body of information available from studies of model membrane systems consisting of phospholipids dispersed in aqueous systems. From such studies using a variety of biophysical methods, it has been shown that alpha-tocopherol intercalates into phospholipid bilayers with the long axis of the molecule oriented parallel to the lipid hydrocarbon chains. The molecule is able to rotate about its long axis and diffuse laterally within fluid lipid bilayers. The vitamin does not distribute randomly throughout phospholipid bilayers but forms complexes of defined stoichiometry which coexist with bilayers of pure phospholipid. alpha-Tocopherol preferentially forms complexes with phosphatidylethanolamines rather than phosphatidylcholines, and such complexes more readily form nonlamellar structures. The fact that alpha-tocopherol does not distribute randomly throughout bilayers of phospholipid and tends to form nonbilayer complexes with phosphatidylethanolamines would be expected to reduce the efficiency of the vitamin in its action as a lipid antioxidant and to destabilise rather than stabilise membranes. The apparent disparity between putative functions of vitamin E in biological membranes and the behaviour in model membranes will need to be reconciled.
 
Article
The onset of lipid peroxidation within cellular membranes is associated with changes in their physiochemical properties and with the impairment of enzymatic functions located in the membrane environment. There is increasing evidence that aldehydic molecules generated endogenously during the process of lipid peroidation are causally involved in most of the pathophysiological effects associated with oxidative stress in cells and tissues. 4-Hydroxy-2-nonenal (HNE), among them, is believed to be largely responsible for cytopathological effects observed during oxidative stree in vivo and has achieved the status of one of the best recognized and most studied of the cytotoxic products of lipid peroxidation. In the present review, I provide a comprehensive summary of HNE, as the product and mediator or oxidative stress.
 
Article
Cationic lipids are positively charged amphiphilic molecules which, for most of them, form positively charged liposomes, sometimes in combination with a neutral helper lipid. Such liposomes are mainly used as efficient DNA, RNA or protein carriers for gene therapy or immunization trials. Over the past decade, significant progress has been made in the understanding of the cellular pathways and mechanisms involved in lipoplex-mediated gene transfection but the interaction of cationic lipids with cell components and the consequences of such an interaction on cell physiology remains poorly described. The data reported in the present review provide evidence that cationic lipids are not just carriers for molecular delivery into cells but do modify cellular pathways and stimulate immune or anti-inflammatory responses. Considering the wide number of cationic lipids currently available and the variety of cellular components that could be involved, it is likely that only a few cationic lipid-dependent functions have been identified so far.
 
Article
This comprehensive review was necessitated by recent observations suggesting that sphingomyelin and derivatives may serve second messenger functions. It has attempted to remain true to the theme of cellular signalling. Hence, it has focussed on the lipids involved primarily with respect to their metabolism and properties in mammalian systems. The enzymology involved has been emphasized. An attempt was made to define directions in which signals may be flowing. However, the evidence presented to date is insufficient to conclusively designate the mechanisms of stimulated lipid metabolism. Hence, the proposed pathways must be viewed as preliminary. Further, the biologic functions of these lipids is for the most part uncertain. Thus, it is difficult to presently integrate this sphingomyelin pathway into the greater realm of cell biology. Nevertheless, the present evidence appears to suggest that a sphingomyelin pathway is likely to possess important bioregulatory functions. Hopefully, interest in this novel pathway will grow and allow a more complete understanding of the roles of these sphingolipids in physiology and pathology.
 
Article
Chloroplasts are the defining plant organelle carrying out photosynthesis. Photosynthetic complexes are embedded into the thylakoid membrane which forms an intricate system of membrane lamellae and cisternae. The chloroplast boundary consists of two envelope membranes controlling the exchange of metabolites between the plastid and the extraplastidic compartments of the cell. The plastid internal matrix (stroma) is the primary location for fatty acid biosynthesis in plants. Fatty acids can be assembled into glycerolipids at the envelope membranes of plastids or they can be exported and assembled into lipids at the endoplasmic reticulum (ER) to provide building blocks for extraplastidic membranes. Some of these glycerolipids, assembled at the ER, return to the plastid where they are remodeled into the plastid typical glycerolipids. As a result of this cooperation of different subcellular membrane systems, a rich complement of lipid trafficking phenomena contributes to the biogenesis of chloroplasts. Considerable progress has been made in recent years towards a better mechanistic understanding of lipid transport across plastid envelopes. Lipid transporters of bacteria and plants have been discovered and their study begins to provide detailed mechanistic insights into lipid trafficking phenomena relevant to chloroplast biogenesis.
 
Article
Phosphoinositides are minor constituents of eukaryotic membranes but participate in a wide range of cellular processes. The most abundant and best characterized phosphoinositide species are phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) and its main precursor, phosphatidylinositol 4-phosphate (PI4P). PI4P and PI(4,5)P(2) regulate various structural and developmental functions but are also centrally involved in a plethora of signal transduction pathways in all eukaryotic models. They are not only precursors of second messengers but also directly interact with many protein effectors, thus regulating their localisation and/or activity. Furthermore, the discovery of independent PI(4,5)P(2) signalling functions in the nucleus of mammalian cells have open a new perspective in the field. Striking similarities between mammalian, yeast and higher plant phosphoinositide signalling are noticeable, revealing early appearance and evolutionary conservation of this intracellular language. However, major differences have also been highlighted over the years, suggesting that organisms may have evolved different PI4P and PI(4,5)P(2) functions over the course of eukaryotic diversification. Comparative studies of the different eukaryotic models is thus crucial for a comprehensive view of this fascinating signalling system. The present review aims to emphasize convergences and divergences between eukaryotic kingdoms in the mechanisms underlying PI4P and PI(4,5)P(2) roles in signal transduction, in response to extracellular stimuli.
 
Article
Antibody or ligand-mediated targeting of liposomal anticancer drugs to antigens expressed selectively or over-expressed on tumor cells is increasingly being recognized as an effective strategy for increasing the therapeutic indices of anticancer drugs. This review summarizes some recent advances in the field of ligand-targeted liposomes (LTLs) for the delivery of anticancer drugs. New approaches used in the design and optimization of LTLs is discussed and the advantages and potential problems associated with their therapeutic applications are described. New technologies are widening the spectrum of ligands available for targeting and are allowing choices to be made regarding affinity, internalization and size. The time is rapidly approaching where we will see translation of anticancer drugs entrapped in LTLs to the clinic.
 
Article
A phospholipase A₂ was identified from MDCK cell homogenates with broad specificity toward glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. The phospholipase has the unique ability to transacylate short chain ceramides. This phospholipase is calcium-independent, localized to lysosomes, and has an acidic pH optimum. The enzyme was purified from bovine brain and found to be a water-soluble glycoprotein consisting of a single peptide chain with a molecular weight of 45 kDa. The primary structure deduced from the DNA sequences is highly conserved between chordates. The enzyme was named lysosomal phospholipase A₂ (LPLA₂) and subsequently designated group XV phospholipase A₂. LPLA₂ has 49% of amino acid sequence identity to lecithin-cholesterol acyltransferase and is a member of the αβ-hydrolase superfamily. LPLA₂ is highly expressed in alveolar macrophages. A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed in alveolar macrophages in LPLA₂(-/-) mice. This defect can also be reproduced in macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In addition, older LPLA₂(-/-) mice develop a phenotype similar to human autoimmune disease. These observations indicate that LPLA₂ may play a primary role in phospholipid homeostasis, drug toxicity, and host defense.
 
Article
Mammalian genomes encode genes for more than 30 phospholipase A₂s (PLA₂s) or related enzymes, which are subdivided into several classes including low-molecular-weight secreted PLA₂s (sPLA₂s), Ca²+-dependent cytosolic PLA₂s (cPLA₂s), Ca²+-independent PLA₂s (iPLA₂s), platelet-activating factor acetylhydrolases (PAF-AHs), lysosomal PLA₂s, and a recently identified adipose-specific PLA. Of these, the intracellular cPLA₂ and iPLA₂ families and the extracellular sPLA₂ family are recognized as the "big three". From a general viewpoint, cPLA₂α (the prototypic cPLA₂ plays a major role in the initiation of arachidonic acid metabolism, the iPLA₂ family contributes to membrane homeostasis and energy metabolism, and the sPLA₂ family affects various biological events by modulating the extracellular phospholipid milieus. The cPLA₂ family evolved along with eicosanoid receptors when vertebrates first appeared, whereas the diverse branching of the iPLA₂ and sPLA₂ families during earlier eukaryote development suggests that they play fundamental roles in life-related processes. During the past decade, data concerning the unexplored roles of various PLA₂ enzymes in pathophysiology have emerged on the basis of studies using knockout and transgenic mice, the use of specific inhibitors, and information obtained from analysis of human diseases caused by mutations in PLA₂ genes. This review focuses on current understanding of the emerging biological functions of PLA₂s and related enzymes.
 
Article
Multiple secretory phospholipase A2 (sPLA2) genes have been identified in plants and encode isoforms with distinct regulatory and catalytic properties. Elucidation of this genetic and biochemical heterogeneity has provided important clues to the regulation and function of the individual enzymes. An increasing body of evidence shows that their lipid products, lysophospholipids and free fatty acids, mediate a variety of cellular responses, including plant growth, development, and responses to stress and defense. This review discusses the newly-acquired information on plant sPLA2s including the molecular and biochemical characteristics, and signaling functions of each isoform.
 
Article
Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality in the United States and in many other countries. Dysfunctional lipid homeostasis plays a central role in the initiation and progression of atherosclerotic lesions. The ATP-binding cassette (ABC) transporters are transmembrane proteins that hydrolyze ATP and use the energy to drive the transport of various molecules across cell membranes. Several ABC transporters play a pivotal role in lipid trafficking. They are critically involved in cholesterol and phospholipid efflux and reverse cholesterol transport (RCT), processes that maintain cellular cholesterol homeostasis and protect arteries from atherosclerosis. In this article we provide a review of the current literature on the biogenesis of ABC transporters and highlight their proposed functions in atheroprotection.
 
Article
Data provided by several investigators is showing conclusively that the mechanisms regulating normal proliferation and differentiation of certain cell populations are upset in EFAD rats. In most studies, a significant increase in the mitotic index was recorded. This has been seen in squamous keratinizing epithelia of the skin and upper alimentary tract (tongue, esophagus and forestomach). Also, an increase of cell proliferation was found in the gastric glands and intestinal crypts of the EFAD mice and rats. Study of the mitotic index of most organs of the EFAD rat is under investigation in our laboratory. Though, a more dynamic approach to evaluating changes in cell proliferation in EFAD such as was carried on by McCullough et al.,28 using cell labeling, will open leads for understanding the role of EFA and presumably their biological active products, such as prostaglandins, in controlling the cell cycle of various populations. Yet, it is apparent that most cell populations characterized by active renewal, and in which mitoses are normally abundant, such as covering epithelia23 are particularly responsive to the EFAD condition.The recognition of urothelial tumors in a small, though significant number of EFAD rats, and the large incidence of atypical hyperplasias suggest that in this nutritional condition abnormal proliferation and tumorigenesis of the transitional epithelium (urothelium) of the urinary passages is favored.The study of the pathology, life span and longevity of the chronically EFA-deficient rat is showing that: (1) Proliferation and differentiation of certain cell populations are abnormal and, as for urothelial cells, neoplastic in nature and (2) these changes increase in frequency with aging.
 
The metabolic fate of dietary lipid in the body. (A) Circulation and metabolic fate of dietary lipid in the body. (B) The main steps and players involved in intestinal LCFA absorption are depicted: (1) micellar dissociation due to LCFA protonation mediated by the acidic microclimate lining the brush border membrane of enterocytes, (2) LCFA cellular uptake, (3) intracellular trafficking involving soluble lipid-binding proteins and (4) triacylgycerol-rich lipoprotein synthesis and exocytosis into the lymph. ACBP, acyl-CoA-binding protein; ACS, acyl-CoA synthetases; CS, cholesterol; ER, endoplasmic reticulum; FA À , ionized long-chain fatty acids; FABPpm, plasma membrane fatty acidbinding protein; FAH, protonated long-chain fatty acids; FATP4, fatty acid transport protein 4; HDL, high density lipoprotein; I-FABP, intestinal fatty acid-binding protein; L-FABP, liver fatty acid-binding protein; HL, hepatic lipase; LPL, lipoprotein lipase; LRP, LDL-related peptide; MTP, microsomal triacylglycerol transfer protein; TAG, triacylglycerol (triglycerides); PL, phospholipids; CE, cholesterol esters; VLDL, very low density lipoproteins.
Synthesis of intestinal lipoproteins: a working model. For a detailed explanation see Section 4. ApoB48, apolipoprotein B48; CM, chylomicrons; DGAT, acyl-CoAdiacylglycerol acyltransferases; FFA, free fatty acids; MTP, microsomal triacylglycerol transfer protein; RER, rough endoplasmic reticulum; SER, smooth endoplasmic reticulum; TAG, triacylglycerol (triglycerides).
Article
Over the two last decades, cloning of proteins responsible for trafficking and metabolic fate of long-chain fatty acids (LCFA) in gut has provided new insights on cellular and molecular mechanisms involved in fat absorption. To this systematic cloning period, functional genomics has succeeded in providing a new set of surprises. Disruption of several genes, thought to play a crucial role in LCFA absorption, did not lead to clear phenotypes. This observation raises the question of the real physiological role of lipid-binding proteins and lipid-metabolizing enzymes expressed in enterocytes. The goal of this review is to analyze present knowledge concerning the main steps of intestinal fat absorption from LCFA uptake to lipoprotein release and to assess their impact on health.
 
Article
This chapter discusses the digestion, absorption, and transport of lipids in ruminant animals. In the simple-stomached animal, the processes of digestion and absorption of dietary fats begin essentially when they reach the small intestine. In the ruminant animal, the situation is very different and the events that occur within the complex polygastric arrangement of the alimentary tract, principally pregastric microbial fermentation of cellulose and other plant polymers not normally hydrolyzed by digestive enzymes, have a profound effect on the chemical and physical nature of the lipids subsequently presented to the small intestine for digestion. Two major processes occur within the rumen, which have an important bearing on the composition and distribution of the lipid components of the digesta and their subsequent metabolism within the intestine. These processes, which are intrinsically bound together, are lipolysis of the dietary lipids and hydrogenation of their unsaturated fatty-acid constituents. These make an immense contribution directly to the lipid metabolism of the host animal after absorption from the rumen and indirectly through their involvement in bacterial and protozoal lipid synthesis.
 
Article
Food-grade nanoemulsions are being increasingly used in the food and beverage industry to encapsulate, protect, and deliver hydrophobic functional components, such as oil-soluble flavors, colors, preservatives, vitamins, and nutraceuticals. These nanoemulsions contain lipid nanoparticles (radius < 100 nm) whose physicochemical characteristics (e.g., composition, dimensions, structure, charge, and physical state) can be controlled by selection of appropriate ingredients and fabrication techniques. Nanoemulsions have a number of potential advantages over conventional emulsions for applications within the food industry: higher stability to particle aggregation and gravitational separation; higher optical transparency; and, increased bioavailability of encapsulated components. On the other hand, there are also some risks associated with consumption of lipid nanoparticles that should be considered before they are widely utilized, such as their ability to alter the fate of bioactive components within the gastrointestinal tract and the potential toxicity of some of the components used in their fabrication (e.g., surfactants and organic solvents). This article provides an overview of the current status of the biological fate and potential toxicity of food-grade lipid nanoparticles suitable for utilization within the food and beverage industry.
 
Top-cited authors
E.n. Frankel
  • University of California, Davis
Douglas R Tocher
  • University of Stirling
Arthur A. Spector
  • University of Iowa
Denis J Murphy
  • University of South Wales
Peter Bramley
  • Royal Holloway