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An Overview of the Modulatory Effects of Oleic Acid in Health and Disease

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Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil, rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi, by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty acid mainly found in the Mediterranean diet.
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Mini-Reviews in Medicinal Chemistry, 2013, 13, 000-000 1
1389-5575/13 $58.00+.00 © 2013 Bentham Science Publishers
An Overview of the Modulatory Effects of Oleic Acid in Health and
Helioswilton Sales-Campos1, Patrícia Reis de Souza1, Bethânea Crema Peghini3,
João Santana da Silva2 and Cristina Ribeiro Cardoso1,*
1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas – Faculdade de Ciências Farmacêuticas de
Ribeirão Preto; 2Departamento de Bioquímica e Imunologia – Faculdade de Medicina de Ribeirão Preto, Universidade
de São Paulo, Ribeirão Preto, São Paulo, Brazil; 3Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais,
Abstract: Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil,
rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also
suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound
healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets
may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi,
by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel
putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by
unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on
inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel
therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty
acid mainly found in the Mediterranean diet.
Keywords: Oleic acid, modulatory effects, cancer, autoimmune and inflammatory diseases, wound healing.
The concep t that specific fatty acids (FA) are necessary
for an appropriate growth of animals including humans was
first introduced by Burr and Burr in 1929, when Wistar rats
were depriv ed of dietary fat and there was an occurrence of a
“new deficiency disease” involving caudal necrosis [1].
However, until 1960s the importance of essential fatty acids
for human health was poorly considered. Their relevance
was primary highlighted in studies which described signs of
clinical deficiency in infants fed skimmed milk-based formula
[2] or in neonates receiving a fat-free parenteral nutrition [3,
4]. Therefore, b ased on a nutritional classification, fatty acids
that are not synthesized by humans and are indispensable for
development and health are known as essential while those
produced by humans are classified as non-essential fatty
acids. In this context linoleic and alpha-linolenic acids are
polyunsaturated fatty acids (PUFA) classified as essential
while monounsaturated fatty acids (MUFA) are classified as
non-essential [5].
The fatty acid classification in MUFA or PUFA is based
on the hydrocarbon bonds in their structural composition.
When a fatty acid has no double bonds in the hydrocarbon
*Address correspondence to this author at the School of Pharmaceutical
Sciences of Ribeirão Preto – USP, Department of Clinical, Toxicological
and Bromatologic Analysis, Av. do Café, s/n – 14040-903 Ribeirão
Preto/SP, Brazil; Tel: 16. 3602 0257; Fax: 16. 3633 6840;
chain it is named saturated fatty acid (SFA) and when it has
one or more double bonds it is classified as MUFA or PUFA,
respectively [6, 7]. Therefore, arachdonic acid [AA, C20:4
(-6)], linoleic acid [LA, C18:2 (-6)], docosahexanoic acid
[DHA, C22:6 (-3)], eicosapentanoic acid [EPA, C20:5 (-
3)] and linolenic acid [LA, C18:3 (-3)] are examples of
PUFA while oleic acid [OA, C18:1 (-9)] is a MUFA, a
non-essential fatty acid that has been recently described as a
regulator of immune function and health.
MUFA contribute to dietary fat consumption in many
parts of the world and in Mediterranean area it constitutes at
least one third of the total fatty acid intake [8]. Olive oil is
one of the most used culinary fat in Mediterranean diet [9]
being mainly composed by the MUFA oleic acid (OA),
which represents 70-80% of olive oil composition, besides
minor phenolic compounds [10]. In the last years many
studies described the contribution of olive oil to general
health, partly due to its high OA content [11-17], which was
demonstrated to lead to a reduction in cholesterol levels,
atherogenesis risk [5, 18-21], host versus graft response [22],
blood pressure and daily anti hypertensive drug intake [23].
In addition OA was demonstrated to induce beneficial anti-
inflammatory effects on auto immune diseases [24, 25],
protective effect on breast cancer and improvement of immune
system function [26-30]. Then, these well-documented
properties reinforce the importance to a better understanding
of the mechanisms of action and physiological changes
caused by oleic acid intake, esp ecially in human health.
2 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
A full and effective immune response to a host threatening
stimuli requires diverse and complementary mechanisms of
inflammation, cell activation, antibody production and
effector reactions, which include innate immune components
like granulocytes, natural killer cells, macrophages and their
soluble mediators, along with a more specialized adaptive
lymphocyte response. Therefore, some evidences suggested
that dietary lipids influence the activity and function of
numerous immune system components. These changes
comprise the modulation of innate and adaptive responses
including antigen presentation, lymphocyte proliferation,
cytokine production, granulocytes and natural killer cell
activity that may be modified by unsaturated fatty acids [31,
32]. So far, many mechanisms have been proposed to
explain the relationship between different fatty acids intake
and the immune system modulation both in humans and
experimental animals.
Regarding innate granulocytes function, an increase in
reactive oxygen species (ROS), that is essential for
neutrophil microbicidal activity, was observed in patients
who received olive oil emulsion when compared to those
who were given soybean oil emulsion [33, 34]. However, no
effect of olive oil emulsion was observed in other inflammatory
and immune parameters such as erythrocyte sedimentation
rate, production of C-reactive protein, TNF-, IL-6, IL-8 and
soluble receptors for IL-2 in humans [35]. Furthermore, the
olive oil intake did not change the mitogen stimulated human
lymphocytes proliferation while in rats there was an
inhibition of this parameter. Indeed, feeding laboratory
rodents a diet rich in olive oil resulted in the suppression of
natural killer cell activity (Fig. 1) [36], mitogen stimulated
proliferation [37, 38] and the expression of receptors for IL-2
and transferrin [37] in spleen lymphocytes. These differences
were probably due to the higher olive oil content provided to
the experimental animals that had reduced proliferation when
fed diets containing a range of 35.6-71.6% of olive oil
(approximately 60-130 g/Kg) in the total fatty acids while
humans received only 18.4% of olive oil content [39, 40].
Thus, in middle aged men who consumed either a control
diet or a diet containing foods enriched in highly refined
olive oil for 8 weeks there was no change in proliferation of
either whole blood cultures or peripheral blood mononuclear
cells in response to concanavalin A (Con A) [39].
However, contradictory findings are reported in the
literature regarding the effects of OA on immune function.
Cury-Boaventura et al. demonstrated that an olive oil-based
emulsion given to healthy volunteers led to decreased ex-
vivo lymphocyte proliferation (Fig. 1), besides having no
effect on neutrophils [33]. Additionally, studies conducted in
rats suggested that an olive oil emulsion, rich in OA, had no
effect in the inhibition of interleukin-2 (IL-2) receptor
expression [41], IL-2 production by lymphocytes, bacteremia
[42], chemotaxis, migration or pro-inflammatory cytokines
released by neutrophils [43], while these effects were
observed with soybean emulsion administration [33]. Then,
the modulatory role of OA on the immune response seems to
be dependent on the amount and the content of fatty acid
received by the subjects, animal species or the immune
parameter evaluated, although most studies provide strong
evidences for a relevant participation of this MUFA in the
immunity control. Moreover, further comparisons among the
effects of olive oil, safflower oil and a high OA sunflower oil
on the immune cell functions suggested that the effects
observed were due to OA rather than to the non lipid
component of olive oil [44].
Adhesion molecules are also imp licated in the immun e
responses, by interfering with the immunological synapse
formation and trans endothelial migration of leukocytes to
the antigen site in the inflammatory reactions. These
molecules also mediate leukocyte traffic to synovial fluid
and tissue in rheumatoid arthritis (RA), as well as the
formation of atherosclerotic plaques dependent on the
leukocyte endothelium interaction in cardiovascular diseases
[8]. A study using human saphenous vein endothelial cells
(HSVEC) preincubated with arachidonic acid (AA),
eicosapentanoic acid (EPA), docosahexaenoic acid (DHA) or
OA prior to stimulation with TNF- showed that OA and
DHA significantly decreased the expression of vascular cell
adhesion molecule-1 (VCAM-1) by HSVEC (Fig. 1) [45].
Other studies showed a decreased expression of the adhesion
molecules CD2, ICAM-1 and LFA-1 on spleen lymphocytes
of rats fed olive oil (Fig. 1) and fish oil containing -3
PUFA [22]. In addition, middle-aged men fed a diet with
18.4% content in MUFA showed a decreased expression of
the leukocyte adhesion molecule ICAM-1 in the peripheral
blood mononuclear cells, after 2 months of diet consumption,
when compared to values from a normal diet control group
[39]. Furthermore, healthy men and women living in a
religious community were subjected to different fat content
in diet during four consecutive dietary periods differing in
the fat content of saturated fatty acid, MUFA, linolenic (-3)
and linoleic (-6) PUFA. There was a lower monocyte
adhesion to endothelial cells and the resistance of low-
density lipoprotein (LDL) to oxidation was greatest during
the MUFA period (Fig. 1) [46].
Besides basic studies, several pre-clinical and clinical
trials have also reported the beneficial effects of OA
consumption in the immune response, especially in
autoimmune diseases. By evaluating the effects of fish oil on
the severity and progression of active human RA, Kremer et
al. observed that olive oil, used as a placebo in these
experiments, had unexpected beneficial effects on the
improvement of clinical aspects of the disease, once this
treatment was associated to decreased macrophage IL-1
production after stimulation with Con A, although not to the
same extent as to the fish oil group supplemented with EPA
or DHA [25]. Linos et al. [24] also demonstrated some
beneficial anti-inflammatory effects of OA consumption on
RA, comparing the relative risk of disease development in
relation to lifelong consumption of olive oil (almost every
day) in a Greek population. This population was four times
less likely to develop RA when compared to those who
consumed olive oil less than six times per month [24]. In
recent years olive oil/OA has been experimentally used to
treat inflammatory bowel disease (IBD) induced experimentally
by dextran sodium sulphate (DSS). Borniquel et al. [47] by
giving OA and a nitrated oleic acid (OA-NO2) subcutaneously
to DSS treated mice observed both in vitro and in v ivo the
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 3
ability of OA-NO2, better than OA, to improve inflammation
and clinical score in this experimen tal intestinal
inflammation (Fig. 1). It is important to note that OA-NO2 is
a product of unsaturated fatty acids, known as nitroalkene,
that is endogenously produced [48, 49] and has anti-
inflammatory properties due to its interactions with numerous
pathways such as nuclear factor-B (NF-B) or signal
transducer and activator of transcription (STAT) [50].
Nitroalkene was already described as a strong activator of
peroxisome proliferator-activated receptor (PPAR ) in
IBD [51]. In another study in which mice were fed different
oils it was observed a lower mortality, lower clinical/
macroscopic intestinal inflammation score and a reduction in
the activity of COX-2 and iNOS in olive oil fed group, when
compared to sunflower oil fed mice [52]. Altogether, these
findings indicate that olive oil or OA present well-defined
anti-inflammatory effects on autoimmune and chronic
inflammatory diseases.
Tissue wounds also trigger various cellular events based
on inflammation like cell migration, angiogenesis,
extracellular matrix deposition and re-epithelialization [53].
Thereby, many biological mediators are necessary to control
these different processes, like nitric oxide (NO), which is
important to skin wound healing since it influences the
functions of fibroblasts, macrophages and keratinocytes during
the healing process [54]. Inhibition of NO synthesis induces
the release of some mediators by fibroblasts and inflammatory
cells which then causes the reduction on collagen deposition
at the site of the wound [55].
Fig. (1). Summary of oleic acid (OA) effects and actions. Highlighted in black are conditions in which OA acts as enhancer such as in wound
closure or drugs absorption. In light grey, the effects of oleic acid in the reduction of inflammation, modulation of leukocytes activity,
enhancement of bactericidal and fungicidal action, inhibition of cancer proliferation and oncogenes expression, reduction of blood pressure
and attenuation of the effects of autoimmune diseases. Note that the real role of OA in leukocytes activity is still a matter of debate.
4 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
MUFA and PUFA can be therapeutically used as an
option to treat cutaneous wounds. Regarding NO, OA
treatment inhibited its early production in contrast to -6 and
-3, which induced higher levels of NO in experimental skin
wounds, respectively, at 48h and 3h post surgery [56]. These
authors also demonstrated that after 5 and 10 days of
treatment of surgically induced skin wounds in mice, the
group treated with OA showed smaller wounds area mainly
when compared to -3 treated group (Fig. 1). Moreover the
OA and the -6 groups had less edema at 48 hours when
compared to control. On the other hand, after 5 days of
treatment, the -3 group showed greater edema and thicker
clot cover than -6 or OA treated groups. The treatment with
-3 induced increased amount of connective tissue fibers
deposition in the wounds site, although OA favored tissue
repair [56].
More recently, Cardoso et al. [57] demonstrated in
BALB/c mice with surgically induced skin wounds, that at
120 h after surgery there was faster wound closure, elevated
levels of collagen III mRNA, tissue inhibitor of metalloproteinase
(TIMP1) and metalloproteinases-9 (MMP9) in OA treated
group in comparison to -3 and control groups. Moreover in
OA group there were lower levels of cyclooxygenase-2
(COX-2) expression, which is important for the production
of pro-inflammatory mediators, when compared to -3
treated wounds. The OA treated group also presented an
increased gene transcription for TNF-, IL-10 and IL-17
when compared to -3 and control groups, especially at 120
h post surgery. The wound inflammatory infiltrate was also
investigated and there was a less prominent detection of
CD11b+, CD4+ and CD8+ cells in OA treated group [57],
thus demonstrating that this MUFA may actually influence
the skin inflammatory process and thus wound repair.
Additionally, another study showed that OA exerts pro-
inflammatory effects on wound healing as observed by
increased neutrophil migration to the lesions, protein and
DNA contents, besides the stimulation of mediators release
by neutrophils such as VEGF- and IL-1, thus accelerating
the wound healing process [58]. This same group showed
recently that oral administration of OA to rats with skin
wounds led to an initial NF-kB activation and increased
TNF- production 1h after tissue injury with a reduction in
pro-inflammatory cytokines 24h later, suggesting an
acceleration of the inflammatory phase of wound healing
after OA oral administration [59]. Therefore, these studies
suggest that OA modulate or have a beneficial effect on
wound closure that is an inflammation-dependent phenomenon.
The effects of OA in the immunomodulation of infectious
diseases are far less investigated than those from other fatty
acids like PUFA. Even though, several studies have tried to
elucidate the possible benefits of olive oil intak e on infectious
events [60-64]. It is known that the cytokines released during
an infectious or inflammatory response, apart from modulation
of the immune system, bring about enhanced lipolysis,
gluconeogenesis, muscle proteolisis and redistribution of
tissue zinc in order to provide substrate for cells of the
immune system and amino acids for the synthesis of acute-
phase proteins [21]. However, although excess inflammatory
reactions may help in the pathogen elimination, it can also
lead to extensive tissue damage.
Regarding the putative immunomodulatory actions of
fatty acids, some studies have investigated the inflammatory
response to TNF- administration or to Escherichia coli
endotoxin in rats previously treated with corn, fish, coconut,
olive oils or butter (rich in OA). The results demonstrated
that especially in groups treated with OA, a suppression in
tissue zinc content, liver protein synthesis and serum
ceruloplasmins levels was achieved when compared to a
corn oil diet or standard laboratory chow [19, 21].
Listeria monocytogenes is a gram-positive facultative
intracellular bacterium that can cause severe infections,
especially in immunocompromised hosts, pregnant women,
newborns and elderly, reaching mortality rate of 20% or
higher. The murine infection with L. monocytogenes is a
well-characterized model for understanding cellular
immunity against intracellular bacteria [65, 66]. Puer tollano
et al. [67] demonstrated in mice experimentally infected with
Listeria monocytogenes and fed a diet rich in olive oil a
better immune response to this bacteria as well as a faster
elimination of the infectious agent along with a lower
mortality rate when compared to a group that had received
fish oil. They also demonstrated an improved macrophage
capability to destroy these pathogens in the olive oil group
(Fig. 1). Moreover, when these animals were reinfected with
Listeria monocytogenes the secondary immune response in
olive oil group was more effective than in fish oil treated-mice
[67]. Additionally, mice infected with L. monocytogenes,
which uses spleen as a supportive environment to survival
[68] and fed fish oil presented a significant increase in spleen
weight at 72 hours after secondary infection, whereas there
was a significant decrease in the olive oil fed group at the
same period evaluated [66]. It was also observed elevated
levels of serum ICAM-1 and VCAM-1 in mice experimentally
reinfected with Lysteria monocytogenes and fed olive oil or
high oleic sunflower oil when compared to fish oil fed
group. These results could suggest a relevant effect of olive
oil in the spleen leukocyte accumulation or bacteria clearance,
in comparison to other dietary fats. In addition, another study
demonstrated that olive oil presents bactericidal activity
against Helicobacter pylori, the main causative agent of
gastric ulcers which may also be related to gastric cancers
development [69].
Considering fungal infections, mice submitted to
isolation stress showed a temporarily delayed clearance of
Paracoccidioides brasiliensis, especially when their diets
were enriched in olive oil in comparison to soybean oil [70].
Thereby, olive oil seems to be less effective in the attenuation of
the stress-induced effects on host defense against this fungus
than soybean oil. It is important to note that psychological
stress, just as the isolation stress, is related to alterations in
many aspects of immune response, such as decreased activity of
natural killer (NK) cells, increased metastasis of tumors
transplanted into mice [71], reduced mitogen-stimulated
lymphocytes proliferation and abnormal production of
cytokines by these cells [72].
Besides modulating cell fatty acid content and
paracoccidioidomycosis, dietary lipids can alter innate
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 5
immune functions that are also essential to pathogens
control. Monocytes and macrophages are able to phagocyte
microorganisms and kill them as an important first line cell
defense [73]. In this context, Martins de Lima-Salgado et al.
[74] observed that high OA content in vitro can increase the
fungicidal capability of macrophages infected with Candida
albicans when compared to other fatty acids such as palmitic
acid and linoleic acid. The authors also demonstrated that
OA induces a sustained effect on reactive oxygen species
(ROS) production and this may be related to the increased
fungicidal activity observed in cells treated with OA.
Overall, the findings above suggested that OA may be
beneficial to patients suffering from diseases that require a
more efficient pathogen control, such as in bacteria or fungal
infections (Fig. 1).
Different epidemiological surveys pointed to the lower
incidence of cancer occurrence in Mediterranean when
compared to Scandinavian countries, the United Kingdom
and the United States, especially those that involve the
intestine, breast, endometrium, skin and prostate [75-79].
One of the most important find ings related to such
observations was associated to Mediterranean dietary habits,
especially the low consumption of meat and high consumption
of fruits, vegetables and mainly olive oil, rich in OA [80].
Furthermore, high OA and olive oil consumption was already
associated to a reduction in the cancer risk development
(mainly breast, colorectal and prostate cancer) (Fig. 1), while
diets rich in total fat and linoleic acid or saturated fatty acid
were related to an increased cancer risk [81].
Llor and Plons [82] developed some in vitro studies to
evaluate the effect of olive oil and/or OA on colorectal
cancer cells and found that olive oil induced apoptosis, cell
differentiation and down regulated the expression of COX-2
and Bcl-2 (Fig. 1), which are associated to inflammation and
apoptosis. It was not demonstrated that OA has direct effects
on COX-2 or Bcl-2 in this study, but the authors showed a
specific induction of apoptosis in HT-29 cells [82]. Olive oil
consumption also influences the initiation, promotion and
progression of carcinogenesis and in these cases tumors
achieved a lower degree of clinical and histopathological
malignancy [83, 84]. In accordance, OA was demonstrated to
play an important chemoprotection role on breast cancer cell
lines. The in vitro treatment of breast cancer cells with OA
suppressed the oncogene Her-2/neu expression that is
overexpressed in approximately 20% of breast carcinomas
and encode the oncoprotein p185 Her-2/neu which controls,
in normal cellular conditions, many cell functions such as
cell differentiation, proliferation and apoptosis. A
deregulation on this protein expression enhances the risk of
cancer development. Moreover, the OA capability to act
synergistically with the monoclonal antibody trastuzumab,
used as a therapeutical drug on cancer by targeting p185
Her-2/neu, was already described by Menendez et al. [85].
Some patients, mainly those who are hospitalized and
require intravenous nutrition therapy need adequate energy
sources which may be provided by essential fatty acids, thus
preventing metabolic disturbances associated to intravenous
feeding of amino acids and glucose [86-88]. The first well-
tolerated lipid emulsion was based on soybean oil, which is
composed mainly by -6 PUFA (linoleic acid) [33]. This
emulsion showed significant immunomodulatory effects in
patients treated with parenteral nutrition then increasing their
susceptibility to infection [61, 89-93]. One possible
mechanism by which lipid emulsion can cause these side
effects may be the induction of leukocyte death [94-97].
Therefore, other lipid emulsions did not induce this
immunosuppressive effect and constituted an alternative to
intravenous emulsion content. Thus, although many reports
point to the modulatory role of OA on the immune system as
discussed before, emulsions containing olive oil have been
suggested to offer an immunologically neutral alternative to
soybean emulsion for use in parenteral nutrition [35, 41-43,
98, 99].
On the other hand, one of the most important cytokines
usually found in metabolic inflammatory process is TNF-,
which is produced by a wide range of leukocytes in
inflammatory conditions, as well as by the adipose tissue
cells. This cytokine is thought to play a central role in the
metabolic syndrome development, which is characterized by
the presence of three or more metabolic disorders, such as
high blood glucose, low high-density lipoprotein cholesterol
(HDL-c), high blood pressure, high serum triglycerides (TG)
levels and abdominal obesity [100-103]. In this case, TNF-
leads to increased insulin peripheral resistance, inhibition of
its secretion and promotion of inflammation [104-110]. A
positive correlation between increased TNF- in type I I
diabetes patients and the development of inflammatory
process in muscle fibers was already demonstrated in
skeletal muscle biopsies [111]. In this context, the potential
of OA to exert pleiotropic effects such as the induction of
insulin production and inhibition of TNF- action was
demonstrated by in vitro studies using a rat pancreatic cell
lineage which displays glucose dependent insulin secretion
(INS-1 cells), in response to a culture medium containing
high glucose levels [112]. The molecular mechanism by
which OA exerted its role in the reversion of TNF- action is
quite varied and PPAR- receptor may be involved, since it
is known that fatty acids and its metabolites are activators of
PPAR-, besides being able to ameliorate the inflammatory
effects of TNF- [1]. Furthermore the translocation of
PPAR- to the nucleus is though to mediate the anti-
inflammatory properties of fatty acids [112]. Thus, OA may
present potential applications and benefits in human health
regarding the prevention of metabolic and nutrition
disturbances in a selective group of patients.
The protective action of OA regular intake on health risk
parameters, especially in cardiovascular disease, is mainly
reported in the Mediterranean area, where people’s diet is
associated to elevated MUFA intake due to higher
consumption of olive oil [113, 114]. So far, the potential of
OA to ameliorate cardiovascular risks may be associated to
an improvement of serum lipoprotein profile (HDL-to-LDL)
in patients with hypercholesterolemia [115, 116], besides an
6 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
enhanced endothelial function due to an increase in flow-
associated vasodilatation in hypercholesterolemic patients
[117] and reduction in inflammation and oxidative stress
[118]. Subsequently, there is a diminishment in the anti-
hypertensive drugs consumption and in the occurrence of
degenerative diseases [119-123] together with a better blood
pressure control both in humans [124] and rats fed a diet rich
in OA (Fig. 1) [125, 126].
The and adrenergic receptors are essential in
controlling central and peripheral blood pressure and these
pathways can be regulated by OA [127] because of its effects
on cell membrane structures [127, 128]. For some time, the
action of olive oil on blood pressure control was considered
to be due to the properties of less representative compounds
of this oil such as -tocopherol, polyphenols and other
phenolic substances [23, 129-132]. However, Terés et al.
[14] demonstrated in vivo , that the high OA content in olive
oil and not its minor compounds, are responsible for the
normotensive effects attributed to olive oil consumption,
both in chronic and acute experimental treatments using
olive oil (Fig. 1) [14]. Furthermore, this MUFA may act
through modulation of membrane lipid structures and cell
signaling platforms, with additional regulation of the 2-
adrenergic receptor pathways that involve G protein-
dependent signaling and results in blood pressure control
[127]. Then, the specific molecular mechanism by which OA
controls blood pressure involves its ability to modulate the
structure of plasma membrane lipids due to a regulatory
pathway associated to the inhibition of G proteins both in
vivo (in humans) and in vitro (cell culture) [127, 133].
Indeed, higher levels of MUFA on cell membrane can
regulate the localization, activity and the expression of other
important signaling molecules raising the production of
vasodilator stimuli (cAMP and PKA) and reducing the action
of vasoconstrictor pathways (inositol-triphosphate, Ca+2,
diacylglycerol and Rho kinases) [133]. To date, membrane
lipids and G proteins levels are altered in experimental
models [134, 135] and in hypertensive subjects [136, 137],
especially after a long-term exposure to olive oil diet [138].
Fibrinogen higher levels have already been described as
an independent cardiovascular risk factor [139] due to its
association to the inflammatory process, initiation of
atherogenesis and growth of atheromatous lesions [140].
Likewise, elevated fibrinogen was reported in coronary,
cerebral disease and peripheral arteries [141]. Then, in a
double-blind crossover study, Oosthuizen et al. (1994)
reported a lowering of plasma fibrinogen levels in women
who received fish or olive oils with high baseline fibrinogen
concentrations [142]. Conversely, another study reported no
significant difference between fish oil supplements and an
olive oil placebo in preventing restenosis after coronary
angioplasty [143].
Fatty acids in general can change the cell membrane
fluidity as well as its surface receptors. Several cell surface
proteins form complex with cell membrane receptors and as
a consequence, many cell functions like those mediated by
MHC expression or cell adhesion molecules are regulated.
Then, the initial events of cellular activation and signal
transduction in specialized cells, including leukocytes, occur
in cell membrane defined areas called lipid rafts [67]. Lipid
rafts are cellular membrane areas composed by sphingolipids
and cholesterol phospholipids [144]. This area acts as an
exclusive site that helps receptors to function and trigger or
sustain cell activation (intracellular signaling pathways) [67],
influen ce on the entry of pathogen in the cell and cytoskeletal
organization [145]. Shaikh et al. [146] suggested that
unsaturated fatty acids may affect lipid raft structure and
function by modifying lipid separations [146]. In addition,
Ehehalt et al. [147] demonstrated that FA uptake is closely
related and depends on lipid rafts integrity. These authors
also showed a close relationship between lipid raft cholesterol
content and FA levels observing an inhibition of FA uptake
greater than 50% by decreasing cellular cholesterol levels
Alternative routes to oral or systemic treatment of a wide
range of diseases, especially those that require the use of
anti-inflammatory drugs are of great interest due to the
occurrence of hepatic or systemic side effects [148]. In this
context, Moreira et al., showed that OA enhances (Fig. 1) the
skin distribution and penetration of Lumiracoxib, by
increasing its local retention both in dermis and epidermis,
thus leading to a gradual and dose dependent drug absorption.
To note, Lumiracoxib is a selective non-steroidal anti-
inflammatory (NSAI) drug developed for the management of
chronic and acute pain through the inhibition of COX-2
activities [149]. Furthermore, El Maghraby et al.
demonstrated that OA h as the ability to penetrate on stratum
corneum by disrupting the intercellular lipid structures [150],
a fact that could explain its action on skin physiology and
drugs absorption.
By investigating the role of OA on NSAI drugs
absorption, others observed that these FA, when administrated
as patches in a membrane controlled transdermal drug
delivery system, may provide the maximum permeability
capacity to ketoprofen when compared to other permeation
enhancers such as polyethylene glycol 400 and propylene
glycol [151]. On the other hand, Santoyo & Yqartua using
piroxicam, which is also classified as a NSAI, showed that a
skin pretreated with OA has adequate drug absorption but
not better than linolenic acid pretreated skin. In addition,
despite the retention of drugs into the skin they demonstrated
that FA pretreatment, with no differences between them,
retains 3 times more drug than no pretreated skin [152].
Similarly, Larrucea et al. (2001) showed an enhanced
capability of OA to improve percutaneous permeability to
tenoxicam after skin pretreatment [153]. These data are in
agreement with those from mice studies, in which Gwak &
Chun (2002) observed and enhanced capability of OA to
improve permeability to tenoxicam [154]. Moreover, OA
when associated to diclofenac induced a higher permeation-
enhancing effect than that induced by saturated fatty acids
such as palmitic acid in rats skin [155].
In summary, this review demonstrated that OA, which is
naturally found in olive oil and is a major component of the
Mediterranean diet, presents different properties that can be
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 7
useful both in the immunomodulation, treatment and
prevention of different types of disorders such as cardiovascular
or autoimmune diseases, metabolic disturbances, skin injury
and cancer, besides exerting proeminent role in drug
absorption. However, further studies are still necessary and
should be conducted in order to better clarify the properties
of this fatty acid in human health and disease, as well as to
provide scientific basis for the future establishment of novel
therapeutic approaches for such disorders based on this
The authors confirm that this article content has no
conflicts of interest.
Declared none.
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Received: July 14, 2012 Revised: November 21, 2012 Accepted: November 26, 2012
... In addition, the oil has a high medicinal value [5]. The low content of saturated fatty acids and high content of monounsaturated fatty acids and polyunsaturated fatty acids in the oil is beneficial to human health [6][7][8]. ...
... The cluster analysis revealed six principal groups of the 18 populations of C. oleifera with a Euclidean distance of five as the threshold ( Figure 5). Population 16,17,11,12,14,15,10,2,3,4,7, and 8 were clustered into the first group, population 9 in the second, population 5 and 6 in the third, population 1 in the fourth, population 13 in the fifth, and population 18 in the sixth. ...
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Camellia oleifera is an important woody edible oil crop in China with high ecological and economical values. It is a traditional oilseed crop with high levels of desirable fatty acids. The fruits of C. oleifera were harvested from 18 geographic provenances in southern China. In this paper, we analyzed the key environmental factors of diverse geographic provenances that caused the variation in the fruit morphology and fatty acid composition (FAC). Our study indicated an average coefficient of variation of fruit width (FW) of 18.63%, and 15.81% for fruit length (FL). The most abundant fatty acids (FA) were oleic acid (C18:1; 70.21–85.23%), followed by palmitic acid (C16:0; 6.93–13.89%) and linoleic acid (C18:2; 5.02–14.26%). In addition, the fruit width had a negative correlation with the equivalent latitude (ELAT) and a positive correlation with the annual mean air temperature (MAT). The fruit length-to-width ratio and oleic acid level had a positive correlation with ELAT but a negative correlation with MAT, annual precipitation (AP), and precipitation of wettest quarter (PWQ). A positive correlation was observed between MAT, AP, and PWQ with palmitic acid. Meanwhile, a negative correlation was found between longitude (LON), maximum temperature of warmest month (MTW), and ELAT and palmitic acid. The cluster analysis indicated six groups for the selected 18 populations. Our results showed the most influential environmental factors for variation in fruit morphology and FAC are ELAT and MAT.
... Other fatty acids, such as myristic and oleic acid, are also reported to have beneficial effects on human health, e.g., the gut microbiota, cancer, obesity-related disorders, and cardiovascular disease [189][190][191][192][193][194]. Although the available amounts in AP are relatively low (below 5% of total fatty acids), a cumulative effect might be conceivable [195]. ...
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The cyanobacterium Arthrospira platensis (Spirulina platensis) is a natural source of considerable amounts of ingredients that are relevant for nutra- and pharmaceutical uses. Different hydrophilic and hydrophobic substances can be obtained by extraction from the biomass. The respective extraction techniques determine the composition of substances in the extract and thus its biological activity. In this short review, we provide an overview of the hydrophilic compounds (phenols, phycobiliproteins, polysaccharides, and vitamins) and lipophilic ingredients (chlorophylls, vitamins, fatty acids, and glycolipids) of Arthrospira platensis. The principal influences of these substances on blood and tissue cells are briefly summarized.
... One of the possible mechanisms by which OA contributes to inflammation is the activation of peroxisome proliferator-activated receptor gamma (PPARγ), which is understood to mediate the reduction of TNFα production and stimulate insulin production [39]. Although our results confirmed greater insulin production after OA supplementation, TNFα concentrations in serum as well as in the adipose tissue were not affected. ...
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Introduction: Monounsaturated fatty acids (MUFA) are understood to have therapeutic and preventive effects on chronic complications associated with type 2 diabetes mellitus (T2DM); however, there are differences between individual MUFAs. Although the effects of palmitoleic acid (POA) are still debated, POA can regulate glucose homeostasis, lipid metabolism, and cytokine production, thus improving metabolic disorders. In this study, we investigated and compared the metabolic effects of POA and oleic acid (OA) supplementation on glucose and lipid metabolism, insulin sensitivity, and inflammation in a prediabetic model, the hereditary hypertriglyceridemic rat (HHTg). HHTg rats exhibiting genetically determined hypertriglyceridemia, insulin resistance, and impaired glucose tolerance were fed a standard diet. POA and OA were each administered intragastrically at a dose of 100 mg/kg b.wt. for four weeks. Results: Supplementation with both MUFAs significantly elevated insulin and glucagon levels, but only POA decreased nonfasting glucose. POA-treated rats showed elevated circulating NEFA associated with increased lipolysis, lipoprotein lipase gene expression, and fatty acid reesterification in visceral adipose tissue (VAT). The mechanism of improved insulin sensitivity of peripheral tissues (measured as insulin-stimulated lipogenesis and glycogenesis) in POA-treated HHTg rats could contribute increased circulating adiponectin and omentin levels together with elevated FADS1 gene expression in VAT. POA-supplemented rats exhibited markedly decreased proinflammatory cytokine production by VAT, which can alleviate chronic inflammation. OA-supplemented rats exhibited decreased arachidonic acid (AA) profiles and decreased proinflammatory AA-derived metabolites (20-HETE) in membrane phospholipids of peripheral tissues. Slightly increased FADS1 gene expression after OA along with increased adiponectin production by VAT was reflected in slightly ameliorated adipose tissue insulin sensitivity (increased insulin-stimulated lipogenesis). Conclusions: Our results show that POA served as a lipokine, ameliorating insulin sensitivity in peripheral tissue and markedly modulating the metabolic activity of VAT including cytokine secretion. OA had a beneficial effect on lipid metabolism and improved inflammation by modulating AA metabolism.
... The BC lipid profile is characterized by around 65-75% of saturated fatty acids, 24-28% monounsaturated fatty acids, and 4-5 polyunsaturated fatty acids [41]. Palmitic acid (about 40%) and oleic acid (21%) are the two most represented total fatty acids [40], confirming the importance of palmitic acid in infant nutrition [42], while oleic acid is involved in other health benefits related to the immunomodulation and to the cardiovascular system [43]. Fat-soluble (A, D, and E) and water-soluble (B-complex) vitamins are both represented in BC (Table 2), being involved in several metabolic processes including bone growth and antioxidant activity. ...
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Colostrum (or first milk) is the food produced by all the mothers in all specific mammalian species, ruminants, monogastric and marine mammalians for their newborns during the first 24–48 h post-partum. Colostrum provides to the neonate all essential nutrients necessary for the first week of life, but the effect of colostrum shows a long-term effect not limited to these first days. Colostrum is considered to be a safe and essential food for human consumption. Some young children can show at the beginning of their colostrum-based diet some side effects, such as nausea and flatulence, but they disappear quickly. In human colostrum, the immunoglobulins and lactoferrin determined show the ability to create natural immunity in newborns, reducing greatly the mortality rate in children. Recent studies suggest that bovine colostrum (BC) may be an interesting nutraceutical food, due to its ability in preventing and/or mitigating several diseases in newborns and adults. This review aims to show the nutraceutical and functional properties of colostrum produced by several mammalian species, describing the different colostrum bio-active molecules and reporting the clinical trials aimed to determine colostrum nutraceutical and therapeutic characteristics in human nutrition.
... Oleic acid is the most representative fatty acid in the regulation of blood lipids and the lowering of blood cholesterol. Its effect on lowering serum cholesterol and low-density lipoprotein is equivalent to that of linoleic acid [26], and oleic acid can also improve the immune response by interfering with macrophage lymphocytes and neutrophils [27]. Polyunsaturated fatty acids (PUFAs) refer to fatty acids containing two or more unsaturated bonds. ...
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Fresh corn is a kind of herbaceous plant with rich nutritive value and a reasonable composition of fatty acids; however, there is little research on methods for the systemic nutritional evaluation of fatty acids in fresh corn. The aim of the present study was to conduct a comparative analysis of the fatty acid profiles of Chinese Huangnuo 9 sweet-waxy corn from the provinces of Inner Mongolia, Jilin, and Heilongjiang by gas chromatography; to establish a nutritional evaluation system according to the impacts of nutrients from fatty acids on human health; and finally, to evaluate, compare and rank fresh sweet-waxy corn grown in different regions. Tocopherols were detected by liquid chromatography in order to demonstrate the anti-oxidation activity of fresh corn’s fatty acids. The fatty acid contents and compositions of the 12 samples from the three regions are significantly different from each other. The nutrient value of the fatty acids in fresh corn was analyzed by factor analysis and a linear structural relation model, followed by the fitting and appraising of the model. The studied fresh sweet-waxy corn 1-4 from Inner Mongolia had the highest γ-tocopherol content and the closest saturated fatty acid:monounsaturated fatty acid:polyunsaturated fatty acid rate to the recommended value. The fatty acid profiles of sweet-waxy corns 2-1, 2-2, and 2-3 were the most diverse, and the comprehensive evaluation result of fresh corn 2-4 was the best; its total fatty acid content was the highest. Fresh corn 3-1 in Heilongjiang had the highest unsaturated fatty acids and lower values in its atherosclerosis index and thrombosis index, which suggested the strongest anti-atherosclerosis and anti-thrombotic ability. This work will give a reference to guide dietary choices and provide data support for dietary recommendations for residents.
Macadamia nuts are an abundant source of the monounsaturated fats (59%), oleic (50%-65%) and palmitoleic acid (12%-30%). As macadamia is generally an outcrossing species, this study focuses on the effect of both the maternal (seed parent) and paternal (pollen parent) genotype on the accumulation of the principal fatty acids in macadamia using a controlled 3×3 pollination trial. Both the seed parent and pollen parent were observed to significantly impact the fatty acid profile of macadamia nut kernels. In addition, the general combining abilities (GCA) of the parental cultivars and specific combining abilities (SCA) of parental crosses were determined, as well as identifying maternal/paternal combinations that could significantly increase palmitoleic acid and oleic acid, or decrease saturated fat concentration. These results provide evidence for the first time that pollen source has a significant impact on the fatty acid profile of macadamia kernels, and that previous reporting of the fatty acid profiles of macadamia cultivars is likely to be variable, due to the unknown genotype of pollen sources.
The odour, particle size distribution, microstructure and nutrient profile of giant panda milk (GPM) was compared with bovine milk (BM) and caprine milk (CM). SDS-PAGE images of GPM showed clear, deep and uncertain bands different from those for BM and CM. GPM displayed significantly higher levels for free amino acids (p < 0.05), as well as more polyunsaturated and monounsaturated fatty acids. An electronic nose distinguished the three samples; GPM had the strongest response values to sensors. The effective diameter and polydispersity index of GPM were significantly higher than BM and CM (p < 0.05), and the same results were also observed in confocal laser scanning microscopy (CLSM) images. A giant panda milk substitute formulation with the following main nutrients is recommended: protein, 36%; fat, 50%; carbohydrates, 8%. It is also necessary to supplement a small quantity of isoglobotriose, and adjust the milk substitute amino acids and fatty acids ratios.
Lipids as a large heterogeneous group of hydrophobic or amphipathic organic molecules constituted by hydrocarbons with the presence of other associated functional groups are involved in a plethora of biological processes. Extensive research into the potential bioactivity of lipids in a variety of disease conditions has been conducted over the years, resulting in a paradigm shift for the pharmaceutical, cosmetic, and food industries. Indeed, historically, lipids were previously used as excipients and/or for their nutritional value in these industries; however, with the introduction of the bioactive lipids concept, these molecules began to be used as the main bioactive ingredients in formulations. Regarding this, the present chapter provides an overview of the paradigm shift occurring in the pharmaceutical, cosmetic, and food industries and includes a critical review of each individual perspective of these industries.
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Quality characteristics of bakery products rely partially on the amount and type of fats in their formulation. This study focused on producing emulsified shortenings with high oleic palm oil fractions to be thermo-mechanically characterized and used in the baking of high-fat cookies. Palm oil and hydrogenated fats were commonly used in bakery shortenings to achieve texture and flavor. However, saturated and trans-fats have been shown to cause detrimental health effects, motivating their replacement by unsaturated fats. High oleic palm oil (HOPO) is a novel oil with lower saturated fat and higher oleic acid compared to traditional palm oil (TPO). High oleic red olein (HORO) is a carotene-rich fraction of HOPO. Emulsified shortenings with 30% saturated fat containing HOPO, HORO, and TPO were produced. All shortenings resulted in similar onset temperatures of crystallization and melting points through DSC. Mid-melting peaks observed on TPO where absent in HOPO and HORO shortenings, reflected in lower hardness and calculated SFC of HOPO and HORO shortenings vs. TPO shortening. However, physical properties of shortening-containing cookies were not statistically different. It was demonstrated how HOPO and HORO can be used as alternative fats to TPO in the making of shortenings to be used in baking applications.
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Animal studies suggest that olive oil is capable of modulating functions of cells of the immune system in a manner similar to, albeit weaker than, fish oils. There is some evidence that the effects of olive oil on immune function in animal studies are due to oleic acid rather than to trace elements or antioxidants. Importantly, several studies have demonstrated effects of oleic acid-containing diets on in vivo immune responses. In contrast, consumption of a monounsaturated fatty acid (MUFA)-rich diet by humans does not appear to bring about a general suppression of immune cell functions. The effects of this diet in humans are limited to decreasing aspects of adhesion of peripheral blood mononuclear cells, although there are trends towards decreases in natural killer cell activity and proliferation. The lack of a clear effect of MUFA in humans may be attributable to the higher level of monounsaturated fat used in the animal studies, although it is ultimately of importance to examine the effects of intakes which are in no way extreme. The effects of MUFA on adhesion molecules are potentially important, since these molecules appear to have a role in the pathology of a number of diseases involving the immune system. This area clearly deserves further exploration
Background: Diet has been reported to influence arterial blood pressure, and evidence indicates that the Mediterranean diet reduces cardiovascular mortality. Objective: The objective was to examine whether the Mediterranean diet, as an entity, and olive oil, in particular, reduce arterial blood pressure. Design: Arterial blood pressure and several sociodemographic, anthropometric, dietary, physical activity, and clinical variables were recorded at enrollment among participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Of these participants, 20 343 had never received a diagnosis of hypertension and were included in an analysis in which systolic and diastolic blood pressure were regressed on the indicated possible predictors, including a 10-point score that reflects adherence to the Mediterranean diet and, alternatively, the score's individual components and olive oil. Results: The Mediterranean diet score was significantly inversely associated with both systolic and diastolic blood pressure. Intakes of olive oil, vegetables, and fruit were significantly inversely associated with both systolic and diastolic blood pressure, whereas cereals, meat and meat products, and ethanol intake were positively associated with arterial blood pressure. Mutual adjustment between olive oil and vegetables, which are frequently consumed together, indicated that olive oil has the dominant beneficial effect on arterial blood pressure in this population. Conclusions: Adherence to the Mediterranean diet is inversely associated with arterial blood pressure, even though a beneficial component of the Mediterranean diet score—cereal intake—is positively associated with arterial blood pressure. Olive oil intake, per se, is inversely associated with both systolic and diastolic blood pressure.
Dietary fats mainly consist of fatty acids esterified to glycerol. For a long time, they have been considered as a condensed source of energy but this view changed completely after the structural and metabolic functions of fatty acids had been recognized.
Background: Oleic acid is the principal fatty acid of olive oil composition and is reported to play a crucial role in its healthy aspects. However, the detailed mechanism of action is poorly understood. Aims: This study aims to elucidate the role of oleic acid in calcium signaling in rat thymocytes, in comparison to linoleic and linolenic acid. Methods: Fatty acids were applied to thymocytes isolated from wistar rats and loaded with Fura-2 to measure calcium signals. Results: The main results showed a concentration-dependent increase in [Ca2+](i) induced by the 3 fatty acids. Raising the number of unsaturations resulted in greater increases. Two different pathways contributed to the increase induced by the polyunsaturated fatty acids: an IP3- independent release from the thapsigargin-sensitive stores and an extracellular calcium entry by econazole and nifedipine-insensitive channels. However, the OA-induced increases in [Ca2+](i) seemed to be due mostly to the Ca2+ recruited from the intracellular stores. Conclusion: This study demonstrates that the fatty acids tested induce increases in [Ca2+](i), in rat thymocytes, with differences in close relation to the degree of unsaturation. Such differences could be responsible for their different physiological action. Copyright (C) 2011 S. Karger AG, Basel
A 10% soybean oil emulsion (Intralipid(R) 10%), used extensively in Europe for intravenous alimentation, has now been clinically evaluated in the United States. Controlled studies have shown that the soybean oil emulsion can be substituted for glucose to supply one-third to two-thirds of the total calories, and can be administered peripherally without significant vein irritation. Essential fatty acid deficiencies, frequently encountered in patients dependent on parenteral alimentation with fat-free solutions, are prevented and corrected by use of this preparation. Data on long-term tolerance to Intralipid(R) 10% infusions are presented for 292 patients treated for more than 6,000 patient days. The soybean oil emulsion was usually well tolerated. Side effects were reported in two of 133 adults and 12 of 159 pediatric patients.
There has been considerable recent interest in the possibility that the plasma membrane contains lipid “rafts,” microdomains enriched in cholesterol and sphingolipids. It has been suggested that such rafts could play an important role in many cellular processes including signal transduction, membrane trafficking, cytoskeletal organization, and pathogen entry. However, rafts have proven difficult to visualize in living cells. Most of the evidence for their existence and function relies on indirect methods such as detergent extraction, and a number of recent studies have revealed possible problems with these methods. Direct studies of the distribution of raft components in living cells have not yet reached a consensus on the size or even the presence of these microdomains, and hence it seems that a definitive proof of raft existence has yet to be obtained.