Salivary Lipids: A Review

Saliva is produced by both large and small salivary glands and may be considered one of the most important factors influencing the behavior of oral cavity homeostasis. Secretion of saliva plays an important role in numerous significant biological processes: Saliva facilitates chewing and bolus formation as well as performing protective functions and determining the buffering and antibacterial prosperities of the oral environment. Salivary lipids appear to be a very important component of saliva, as their qualitative and quantitative composition can be changed in various pathological states and human diseases. It has been shown that disturbances in salivary lipid homeostasis are involved in periodontal diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes and Sjögren's syndrome). However, little is known about the role and composition of salivary lipids and their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins. The purpose of this review paper is to present the latest knowledge on salivary lipids in healthy conditions and in oral and systemic diseases.


Salivary glands and saliva
2][3][4] Depending on the nature of saliva and its constituent cell types, the following glands can be distunguished: purely serous salivary glands, known as the alveolar salivary glands (e.g. the parotid gland and von Ebner's glands, located at the base of the tongue); purely mucous glands called tubular salivary glands (a plurality of small submucosal glands); and mixed tubulo-alveolar salivary glands. 3,4The latter glands may occur with a greater number of mucous cells (in the sublingual glands mucosal cells represent approx.70%) or a predominance of serous cells (in the submandibular glands serous cells represent 80%).
Within a day, the salivary glands produce an average of 1000-1500 mL of saliva when at rest; stimulation may increase the amount of saliva secreted by several times. 5,6n the absence of stimulation, the parotid, sublingual and minor salivary glands provide about 25%, 7-8% and 7-8%, respectively, of the whole saliva flow.The submandibular gland produces 60% of the unstimulated whole saliva (UWS) flow.When the salivary flow is stimulated, the parotid gland contribution increases by 10-15%, while the remaining salivary glands do not significantly increase saliva secretion. 3,4,6,7][11]15 Saliva fulfills a variety of functions in the oral cavity.It is the liquid medium of the oral cavity ecosystem, providing hydration of the teeth and mucous membrane surfaces, thereby allowing articulation and swallowing.Saliva determines the protection of the oral tissues against biological, mechanical and chemical stimuli; allows the perception of taste and temperature; and is responsible for initial food digestion. 164][25] Salivary proteins are well characterized, but data for characterizing salivary lipids and their functions is scarce and controversial. 16,21

A brief review of lipids
There are many definitions of lipids.Previously, lipids were defined as non-polar compounds insoluble in water but easily soluble in organic solvents. 26Christie describes lipids as "fatty acids and their derivatives, and compounds biosynthetically or functionally related to them". 27o facilitate a comprehensive worldwide classification of lipids, the International Lipid Classification and Nomenclature Committee, with the participation of the LIPID MAPS Consortium, divided lipids into 8 main groups: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids and polyketides. 28,29The first 5 of these groups of lipids are found in saliva, so the authors decided to present briefly the biochemical characteristics of these lipids.It is worth mentioning that many previous works about salivary lipids use the old division of lipids into neutral lipids, glycolipids and phospholipids, which can be quite confusing. 28,29

Free fatty acids
Free fatty acids are the primary component of salivary lipids. 30Free fatty acids are composed of a hydrocarbon chain terminated by a COOH group.The presence of a repeating series of CH 2 -determines the hydrophobic nature of the fatty acids, while the COOH group is hydrophilic. 26,31The proportion of hydrophilic and hydrophobic groups in the molecule accounts for the amphipathic nature of free fatty acids.
Due to the number of carbon (C) atoms, free fatty acids can be divided into short-(< 6 C), medium-(8-14 C), and long-chain (> 16 C) free fatty acids; however, the most common molecules usually contain from 4 to 30 carbon atoms. 32Furthermore, saturated and unsaturated free fatty acids can be distinguished.In the body only unsaturated free fatty acids can be produced, in which the double bond is at position ω-9.Linoleic acid (ω-6) and α-linolenic acid (ω-3) cannot be synthesized by humans and must be provided by food.They are referred to as essential unsaturated fatty acids. 32

Glycerolipids
Glycerolipids include all glycerol-containing lipids, among which the largest group are acyloglycerols (esters formed from fatty acids and glycerol).Acylglycerols exist in various physical forms: monoacylglycerols (MGs), diacylglycerols (DAGs), and triacylglycerols (TGs); triacylglycerols are more plentiful than the other 2 groups. 28,29n contrast to MGs and DAGs, TGs do not form dispersed micelles. 32lyceroglycans are another subclass of glycerolipids, characterized by one or more sugar moieties attached to glycerol via a glycosidic linkage. 29,33ne of the most numerous subgroups of glycerolipids are glycerophospholipids (phospholipids, PH).The common structural element of this class of compounds is phosphatidic acid (PA).The phosphate group of PA can be combined through an ester bond with a compound containing a hydroxyl group, for example choline, ethanolamine, serine, inositol or another glycerol, forming a phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and diphosphatidylglycerol.Among linked fatty acids, acids attached at the C1 carbon atom are typically saturated, while those attached at the C2 atom are unsaturated with one or more double bonds. 29,31,32lycerophospolipids consist of a subset of ether phospholipids, which may contain both ester and ether linkages.This group includes plasmalogens and a platelet activating factor (PAF). 29,31,32 In the plasmalogens, glycerol is attached at carbon atom C1 by an ether linkage to the long chain in the aldehyde enol form.There are 3 classes of plasmalogens: phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. 29,31,32phingolipids are lipids that comprise aminoalcohol instead of glycerol: sphingosine or dihydrosphingosine. 29,31,325][36] A ceramide is a precursor of sphingomyelin and glycosphingolipids.Glycosphingolipids form a polar sugar chain (consisting of one or more monosaccharides), which is bonded O-glycosidically to the ceramide by a hydroxyl group at the C1 atom of sphingosine.Depending on the type of sugar chain, the following are distinguished: neutral glycosphingolipids, containing neutral saccharides (e.g.galactosylceramide and glucosylceramide); acidic glycosphingolipids (gangliosides containing one or more sialic acid residues); and sulphatides, containing a sulfonic acid group.Another group of glycosphingolipids, which has not yet been demonstrated in saliva, consists of basic glycosphingolipids and amphoteric glycosphingolipids. 28,29holesterol is a monohydroxy cyclic unsaturated alcohol, which is of exogenous origin or which may be synthesized de novo in the cytoplasm and endoplasmic reticulum of hepatocytes. 37In body fluids, cholesterol is associated with lipoproteins.It is a major component of cell membranes (with the exception of the mitochondrial membrane) and is present in the cytoplasm in the esterified form with fatty acids. 31,32,38hospholipids, cholesterol and sphingolipids are a structural and functional building material for the cell and intracytoplasmic membranes.Their presence determines the flexibility, fluidity and permeability of these membranes.It should be emphasized that phospholipids may play an important role as second messengers and in the processes of salivation. 39This group includes inositol phospholipids.Neurotransmitters, such as acetylcholine, norepinephrine and substance P, connecting with their membrane receptors, activate G proteins, in particular protein GP(q).This protein activates phospholipase C, which hydrolyzes membrane phosphoinositol to form phosphatidylinositol-4,5-diphosphate (IP2).Phospholipase C phosphorylates cellular proteins that stimulate the processes of gene expression and cell proliferation, as well as activate membrane channels in the cell.It also increases the synthesis and secretion of proteins by the follicle cells and ducts of the salivary glands.IP3 is released from the membrane into the cytoplasm, where it binds to specific receptors in the membrane of the endoplasmic reticulum, which opens the channels for calcium ions and initiates the production of initial saliva. 6,10

Salivary lipids in health
Lipids in saliva obtained from the major salivary glands were first detected by Doubleday in 1909. 40][43][44][45] Later precise quantitative analyses of lipids focused not only on the major groups of lipids, but also on fatty acids constituting individual groups of lipid.The data on the total lipid concentration in stimulated submandibular and parotid saliva is controversial, since they vary from 0.91 mg/100 mL to 9.52 mg/100 mL and from 0.21 mg/100 mL to 9.24 mg/100 mL, respectively. 46,47owever, early qualitative analyses of the lipids in saliva are similar in all available works in this field.Larsson et al. and Slomiany et al. demonstrated that in parotid and submandibular saliva more than 99% and 98% of lipids, respectively, were non-polar. 46,47The neutral lipids were represented by cholesterol and its esters, free fatty acids and tri-, di-as well as monoglycerides, which was confirmed by subsequent studies by Tomita et al. and Brasser et al. 48.49Brasser et al. also identified other neutral lipids, namely squalene and wax esters, and they found that salivary lipids were similar to the profile of skin surface lipids.The only polar lipids identified by Larssen et al. were phosphatidylcholine, phosphatidyletanolamine and sulphatidie, present in both parotid and submandibular fluid; these findings were in agreement with Slomiany et al. 46,50 In another work, Slomiany et al. demonstrated that parotid and submandibular saliva also contain glycolipids: glyceroglicolipidis and glycosphingolipids. 51The latter were represented by galactosyl ceramide, glucosylceramide and lactosylceramide, and their content varied from 0.5% to 2% of the total salivary lipids.Neutral glyceroglicolipids accounted for approx.60% of the total glyceroglicolipids, where hexa-and octaglucosylglyceroglucolipids predominated.Sulfated compounds were represented by tri-and tetraglucosylglucolipids. 51The non-estrified (so-called free) salivary fatty acids -primarily palmitic acidwere the most abundant, followed by stearic, oleic and linoleic acids.Other non-estrified fatty acids were present at concentrations of less than 1µM. 52Tri-, di-, and monoglycerides were composed mainly of palimitic and stearic acid, while cholesteryl esters were characterized by the presence of large amounts of residues of palimitic, stearic and oleic acids.Salivary phospholipids included both saturated and unsaturated fatty acids ranging in size from 12 to 26 carbon atoms, wherein palmitic, stearic, oleic and eruic acids were present in the largest quantities. 47The lipid core of the glyceroglycolipids consisted mainly of glyceryl monodocosyl, monoheneicosyl and monoeicosyl alkyl ethers as well as palimitic, stearic and eruic fatty acids. 53hile the content and the composition of parotid saliva lipids do not differ significantly from those of submandibular saliva, and stimulation does not significantly change the fatty acid content or the lipid profile of saliva, considerable differences have been found in minor salivary gland lipids. 45Slomiany et al. showed that 32.4% of the total lipids were neutral lipids, 44.6% were glycolipids and 23% phospholipids.The total amount of lipids in labial saliva was estimated to be 423.8µg/mL of saliva. 54f the total neutral lipids, 43.8% was comprised of free fatty acids, 26.9% was cholesteryl esters, 15.4% triglycerides, 11.6% cholesterol and approx.3% was made up of mono-and diglycerides.The free fatty acids, cholesteryl esters and triglycerides mainly included palmitic, oleic and erucic acids.Glycolipids were represented by glyceroglicolipids and glycosphingolipids.Glycosphingolipids were represented by glucosylceramide and lactosylceramide; their content in saliva ranged from 0.5% to 1.3% of the total lipids.Sulphated glyceroglycolipids, amounting to 25.4% of the total glycerglycolipids, were primarily tri-and tetrglucosyl compounds.Neutral glyceroglicolipids were demonstrated to be mono-, di-, tetra-, hexa-and octaglucosyl glyceroglucolipids; the last two were predominant, and accounted for 61.6% of the total glyceroglucolipids.The glycolipids were rich in oleic (30.1%) and erucic (19%) acids.Oleic acids (38.9%) were the main lipid component of the phospholipids, which represented 23% of the total labial lipids, (mainly phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine).
The total labial salivary lipids are 4-5 times more numerous than parotid and submandibular salivary lipids, and show a higher percentage of phospholipids and glycolipids.One possibility is that these differences may reflect the different processes in which serous and mucous cells secrete their products, which was explained by Tandler and Poulsen. 55They suggested that mucous cells of the labial salivary glands secrete their products in a partly apocrine manner in which the release of the contents of the secretory vesicles is accompanied by the loss of part of the cell membrane.Therefore, the discharge of such cells contains lipids as part of the cell membrane (i.e.phospholipids and sphingolipids).It is also possible that the glycoproteins synthesized by cells of the mucous labial gland may combine with lipids of the cell membrane, and these cells are then secreted into the saliva.
On the other hand, the observed differences could be due to the interaction between lipids and proteins suspended in then aqueous solution of saliva.The relationship between salivary lipids and the protein components of saliva and the extent of interaction between them were partly demonstrated by Slomiany et al., who measured the distribution of lipids in the fractions of parotid and submandibular saliva following Bio-Gel A-50 column chromatography. 56Over 50% of the submandibular salivary lipids, in particular glycolipids, free fatty acids, phospholipids and cholesterol, were detected in the fraction of saliva rich in mucins.In the parotid saliva, free fatty acids were detected in the fraction deprived of carbohydrates, whereas cholesteryl esters and phospholipids were associated with the carbohydrateabundant fraction.
The physical state of the lipids present in saliva is unknown.Since lipids are practically insoluble in water, they must be complexed with the carrier in order to exist in the saliva.To date, the existence of 2 types of interactions between proteins and lipids has been demonstrated, i.e. hydrophobic and covalent interactions.Hydrophobically bound lipids are represented by neutral lipids, glycolipids and phospholipids; the only covalently attached lipids are fatty acids. 57,58In a hydrophobic amino acid, side chains participate in the hydrophobic binding.These side chains are located on the protein surface, coming in contact with the hydrophobic parts of the lipids.The covalent bond is created, however, by the commonality of one or more pairs of electron-binding atoms. 31It has been shown that in the submandibular glands most hydrophobic interactions with lipids are combinations with MUC5B (50%) and MUC7 (30%).These bonds are very strong and resistant to urea and cesium salts. 59,60Slomiany et al. thought that lipids produced in the parotid glands exist as lipoproteins, and the main glycoprotein taking part in the interactions between proteins and lipids may be a prolinerich glycoprotein (PRG). 47he presence of such lipid carriers was recently demonstrated in the saliva of healthy subjects that showed the presence of apolipoprotein B. 61 However, little is known about the fragments of glycoproteins, where hydrophobic interactions with the lipids present in saliva occur.Salivary mucins contain highly glycosylated regions and regions devoid of carbohydrate moiety. 11he removal of non-glycosylated regions of mucins was associated with a decrease in the phospholipid content as well as an increase in the number of glycolipids (the content of neutral lipids did not change significantly).These observations suggest that phospholipids may interact hydrophobically with non-glycosylated glycoproteins, while glycolipids bind to the glycosylated parts of mucins. 59,60atty acids are combined through an ester linkage with non-glycosylated regions of salivary glycoproteins, mainly large-and low-molecular mucins.In this bind-

Salivary lipids and systemic diseases
There is little data on the nature and content of salivary lipids in systemic diseases.Cystic fibrosis is an innate genetically determined human disease involving impaired secretion by the exocrine glands, including the salivary glands.2][73][74] They showed that saliva from cystic fibrosis patients differs from the saliva from healthy controls with respect to the lipid content and composition.Submandibular saliva from cystic fibrosis patients contained 66% more lipids than the saliva of the healthy controls.The same neutral lipid composition was found in the saliva of healthy individuals and in the patients with cystic fibrosis, but their percentages were significantly different.The saliva of the cystic fibrosis patients contained significantly more fatty acids (54%), triglycerides (35%) and cholesterol (42%) than the saliva of the healthy subjects.The phospholipid content in the saliva of the cystic fibrosis patients was twice as high as in the saliva of healthy individuals, with no differences in the proportion of individual phospholipid classes in the 2 types of saliva samples.In the cystic fibrosis patients' saliva the presence of 0.2-0.5% glycosphingolipids was demonstrated, in addition to the glycorolipids occurring in the healthy controls' saliva.These patients' saliva contained significantly higher concentrations of di-and octaglucosyl glyceroglucolpids, while the saliva of the healthy individuals presented significantly higher levels of mono-and hexaglucosyl glyceroglucolipids.The acidic tetraglucosyl glyceroglucolipid constituted 80% of the sulfated glyceroglucolipids in the healthy individuals' saliva and 59% of the sulfated glyceroglucolipids in the cystic fibrosis patients' submandibular saliva.No significant differences were observed in the fatty acid composition of the lipid fraction of normal and cystic fibrosis saliva.Other studies by A. Slomiany et al. and B.L. Slomiany et al. demonstrated, however, that submandibular saliva of cystic fibrosis patients was characterized by significantly elevated levels of covalentlybound fatty acids. 57,75Those authors hypothesized that the elevated levels of neutral lipids in the cystic fibrosis saliva were the result of increased transition of lipids from the blood, since lipids are known to be increased in the serum of cystic fibrosis patients. 76Another theory was that the increase in neutral lipid levels may be a result of increased synthesis and secretion of salivary proteolipids, since it has been shown that other salivary proteins are also elevated. 72Elevated concentrations of ing, hydroxyl groups of serine, threonine and tyrosine may be involved. 62,63Most frequently, covalent combinations occur: palmitic, stearic, erucic and oleic acids. 64,65t has been shown that the attachment of a fatty acid takes place during the biosynthesis of salivary mucin in mucosal cells and occurs at the end of the processing of oligosaccharide chains, just prior to the formation of polymeric high-molecular-weight mucin.In addition, the connection of a fatty acid is catalyzed by a specific fatty acyl transferase and takes place in the region of a non-glycosylated protein chain; however, fatty acids are attached as hydroxy esters rather than thiol esters.Fatty acyl transferase activity was demonstrated not only in the mucus-secreting submandibular, sublingual and minor salivary glands, but also in the serous parotid glands.Because the major proteins synthesized by parotid glands are rich in glycoproteins, it is highly likely that PRG is acylated with fatty acids. 62,63hree sources of lipids in human saliva are considered: serum component transudation, exfoliative cells and salivary gland secretion. 66,67It has been demonstrated that saliva, serum and cell membrane do not differ significantly with respect to neutral lipids and phospholipids, but they differ markedly with respect to glycolipids.The glycolipids occurring in serum and cell membranes are comprised mainly of glycosphingolipids, while mainly glyceroglycolipids are encountered in saliva. 51,68Moreover, given the fact that serum contains 50-60 times more lipids than saliva, neutral lipids and phospholipids could originate mainly from serum, as has been demonstrated for cholesterol.Salivary cholesterol accounts for 15% of the neutral lipids in saliva, and men show more salivary cholesterol than women, both of which are true of serum; moreover, a positive correlation between cholesterol levels in saliva and in serum suggests that a high percentage of the salivary cholesterol originates from serum, which is in agreement with Slomiany et al. 37,47 A thorough analysis of the contribution of serum and membrane lipids other than cholesterol demonstrates that only a small amount (less than 2%) is plasma-born or is a result of cell exfoliation. 45everal pieces of evidence point to the fact that salivary lipids mostly originate from the salivary glands.It has been shown that the biosynthesis of triglycerides, phospholipids, sulfated lipids and glyceroglycolipids takes place in the salivary glands. 69,70Salivary glands contain 2 different sulphonyl transferases, carrying sulfate groups on the sugar chain of glycolipids.The 1 st enzyme, present in the microsomal fraction, is transferred by the sulfate groups on the sugar chain of glyceroglycolipids, which are the main glycolipids of human saliva.The 2 nd enzyme is present in the cytoplasmic fraction and is responsible for the sulfation of sugar chains of sphingolipids, which represent the main ingredients of the plasma membrane.It is therefore apparent that salivary glands synthesize both secretory and structural lipids.phospholipids and the presence of glycosphingolipids in cystic fibrosis patients' submandibular saliva may be due to the presence of membrane lipids in an aqueous solution of saliva, and may also be the evidence of the existence of salivary abnormalities associated with the secretion of important proteins by cystic fibrosis patients.
Intracellular lipid accumulation in the salivary glands of diabetic rats has been observed, but it was greater in the parotid than in the submandibular or sublingual glands. 77,78Morris et al. were the first to investigate the fatty acid profile, the time course of fatty acid accumulation and the effect of insulin treatment on salivary gland lipids in induced diabetes in a rat model. 77hey observed that stearic acid (C18:0) and linoleic acid (C18:2w6) showed a significant increase in all the salivary glands over 4 weeks after the streptozotocin injection to induce diabetes.In contrast, oleic acid (C18:1w9) was significantly down-regulated in the parotid gland after 3 and 4 weeks, which was in agreement with Mahay et al. 79 Decreases in arachidonic acid were significant in the submandibular gland in 3 weeks and in the parotid gland in 2 weeks of experimental diabetes.Insulin treatment decreased the amount of stearic and linoleic acids in the submandibular and parotid glands as compared to the controls.The authors concluded that the decreases in C18:1w9 and C20:4w6 may be a result of inhibition of desaturase enzymes, which are known to be stimulated by insulin. 80A lack of insulin results in the accumulation of saturated (C18:0) and less unsaturated fatty acids (C18:2w6) as well as an increase in C18:2w6/C18:1w9 ratios.The latter is probably a result of the fact that the amount of linoleic acid is constant, because it comes from the diet, but cannot be desaturated and elongated, while oleic acid cannot be produced from stearic acid.The authors also posited that the accumulation of saturated and less unsaturated fatty acids may be due to a decrease in the consumption of lipids in the synthesis of cell membranes of secretory vesicles.The accumulation of saturated and less unsaturated fatty acids alter membrane structure and fluidity, as well as membrane enzyme function and the secretory function mechanism. 79,81Treatment with insulin showed that the effects of diabetes on salivary lipids are rapid and totally reversible.
Salivary glands are a major target organ of inflammation in the course of Sjögren's syndrome (SS). 82,83n immunohistological analysis of the salivary glands of SS patients has disclosed lymphocytic infiltration with a predominance of T lymphocytes, especially CD4 + cells (the ratio between CD4 + and CD8 = 2:1), as well as a reduced number of B lymphocytes and macrophages, which may be the immediate cause of destruction and dysfunction of the salivary glands. 846][87][88] Parotid salivary lipid analyses have demonstrated that patients with SS had twice as many total lipids as healthy controls, 4 times as many glycolipids and 20 times more phospholipids.Neutral lipids in SS patients contain a higher percentage of mono-, di-and triacyloglycerols and cholesterol than healthy controls, and a lower percentage of cholester- The lipid composition of parotid saliva in young men and changes caused by stimulation There were no significant differences in the composition of neutral and polar lipids in the parotid saliva as a result of stimulation.45 The lipid content of parotid and submandibular saliva from caries-susceptible and caries-resistant patients The levels of phospholipids and neutral lipids (i.e.free fatty acids, triglycerides and cholesterol esters) were significantly lower in the parotid and submandibular saliva of caries-resistant patients.

91
The relationship between high-molecular-weight mucus glycoprotein and covalently bound lipids from stimulated submandibular saliva of caries-susceptible and caries-resistant patients with blood type A The submandibular saliva from caries-susceptible and caries-resistant patients are characterized by a different quantitative composition and different physiochemical characteristics of salivary mucus glycoproteins and covalently bound lipids.

51
The relationship between salivary lipids and proteins and glycoproteins in human saliva Parotid and submandibular lipids show specific associations with the proteins and glycoproteins in human saliva.56 The lipid composition of stimulated human labial gland saliva Of all the salivary lipids, 44.6% were glycolipids, 32.4% neutral lipids, 23% phospholipids.50 The lipid composition of dental plaque from cariessusceptible and caries-resistant patients Plaque maturation is associated with elevated levels of neutral lipids and phospholipids, as well as reduced glycolipid content.92 The quality and quantity of neutral lipids in parotid, submandibular and whole stimulated human saliva Cholesteryl esters, cholesterol, triglicerydes, diglicerydes, monoglicerydes and free fatty acids accounted for 96-99% of the total salivary lipids.46 The lipid and protein content in stimulated parotid and whole saliva from caries-susceptible and caries-resistant women The lipid and protein content was significantly elevated in the parotid saliva from caries-susceptible patients.
ol esters.A phospholipids profile showed a significant increase in phosphatidylcholine in SS, while a profile of glycolipids revealed an increase in sphingomielin. 89ore recently, Tishler et al. identified eicosanoids in the saliva of SS patients. 90They demonstrated a significant increase of prostaglandin E 2 and thromboxane E 2 in mixed saliva from SS individuals as compared to healthy controls and xerostomic patients.They stated that elevated concentrations of eicosanoids in the saliva of SS patients could be a good marker of an inflammatory process in the salivary glands in the course of this disease and could help to identify patients suffering from xerostomia, which may result from other diseases.The results of the main studies about human salivary lipids in health and disease are summarized in Table 1.

Summary
Salivary lipids are among the most essential cellular components of human saliva.In the oral environment they determine the flexibility, fluidity and permeability of cellular membranes and participate in intercellular transport and the signal transduction pathways between the salivary glands and other tissues.Although the qualitative and quantitative content of salivary lipids can change in various pathological states and diseases (e.g.cystic fibrosis, diabetes and Sjögren's syndrome), little is known about the role and composition of salivary lipids, and about their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins.Only accurate knowledge of the qualitative and quantitative composition of lipids and their role in the oral cavity will make it possible to understand better the pathological processes occurring in the oral cavity and in the parotid and submandibular salivary glands.There is, therefore, a need for further research on the role of salivary lipids in both health and disease.

Table 1 .
An overview of major studies about salivary lipids in health and disease