Conjugated linoleic acid (CLA) consists of a group of positional
and geometric fatty acid (FA) isomers of linoleic
acid (C18:2; cis-9, cis-12 octadecadienoic acid).
CLA isomers are found naturally in ruminant meats and dairy
products due to biohydrogenation of linoleic or linolenic
acids in the rumen of these animals. Larger quantities of
CLA are chemically synthesized for use in dietary supplements
or fortified foods. Initially identified as a potential
anti carcinogen, CLA has been reported to prevent obesity,
diabetes, or atherosclerosis in different animal and
cell models, depending on the doses, isomers, and models
used. Potential mechanisms for preventing these diseases
include inducing cancer cell apoptosis, increasing
energy expenditure and delipidating adipocytes, increasing
insulin sensitivity, or reducing aortic lesions. However,
unequivocal evidence in human participants is
still lacking. Ironically, potential side effects of CLA
supplementation include chronic inflammation, insulin
resistance, and lipodystrophy. Long-term, well-controlled
clinical trials and more mechanistic studies are needed to
better understand the true potential health benefits versus
risks of consuming CLA isomers and their mechanisms
CHEMISTRY AND SYNTHESIS OF CLA
Natural Synthesis of CLA Isomers
CLA isomers are produced naturally in the rumen of ruminant
animals by fermentative bacteria Butyrivibrio fibrisolvens,
is in the mammary gland via -9-desaturase of trans-11, octadecanoic
acid (1). Thus, natural food sources of CLA are
dairy products including milk, cheese, butter, yogurt, and
ice cream and ruminant meats such as beef, veal, lamb, and
goat meat (2–4). The cis-9, trans-10 (9,11) isomer
(i.e., rumenic acid) is the predominating CLA isomer in
these products (∼80%), whereas the trans-10, cis-12 (10,12)
isomer represents approximately 10%. Although several
other isoforms of CLA have been identified, the 9,11 and
10,12 isomers appear to be the most biologically active
(5). Levels of CLA isomers in ruminant meats or milk can
be augmented by dietary manipulation, including feeding
cattle on fresh pasture (6) or by adding oils rich in linoleic
acid (e.g., safflower oil) or ingredients that alter biohydrogenation
of linoleic acid (e.g., ionophores) to their diet (7).
Structures of linoleic acid, cis-9, trans-11 CLA, and trans-10,
Chemical Synthesis of CLA Isomers
Because of the relatively low levels of CLA isomers in
naturally occurring foods that are high in fat content, the
chemical synthesis of CLA has been developed for making
supplements and for fortifying foods. CLA can be
synthesized from linoleic acid found in safflower or sunflower
oils under alkaline conditions, yielding a CLA mixture
containing approximately 40% of the 9,11 isomer and
44% of the 10,12 isomer (reviewed in Ref. 8). Commercial
preparations also contain approximately 4% to 10% trans-
amounts of other isomers.
Conjugated Linoleic Acid
CLA Content of Various Foods
Food mg/g fat Food mg/g fat
- Corned beef 6.6 Condensed milk 7.0
- Lamb 5.8 Colby cheese 6.1
- Fresh ground beef 4.3 Butter fat 6.1
- Salami 4.2 Ricotta 5.6
- Beef smoked sausage 3.8 Homogenized milk 5.5
- Knackwurst 3.7 Cultured buttermilk 5.4
- Smoked ham 2.9 American processed cheese 5.0
- Veal 2.7 Mozzarella 4.9
- Smoked turkey 2.4 Plain yogurt 4.8
- Fresh ground turkey 2.6 Butter 4.7
- Chicken 0.9 Sour cream 4.6
- Pork 0.6 Cottage cheese 4.5
- Egg yolk 0.6 Low fat yogurt 4.4
- Salmon 0.3 2% milk 4.1
- Vegetable oils Medium cheddar 4.1
- Safflower oil 0.7 Ice cream 3.6
- Sunflower oil 0.4 Parmesan 3.0
- Peanut 0.2 Frozen yogurt 2.8
- Sources: Based on values reported in Refs. 2–4; and the University of Wisconsin
Food Research Institute (Dr. Pariza, Director).
PHARMACOKINETICS AND EFFICACY OF CLA
Human and Animal Studies
As with other long chain unsaturated fatty acids (FA)s,
CLA is absorbed primarily in the small intestine, packaged
into chylomicrons, and distributed to extrahepatic tissues
having lipoprotein lipase (LPL) activity or returned to
the liver via chylomicron remnants or other lipoproteins.
The average daily intake of CLA is approximately 152 to
212 mg for nonvegetarian women and men, respectively
(9), and human serum levels range from 10 to 70 mol/L
after supplementation (10,11).
One major discrepancy between animal and human
studies is the dose of CLA administered (i.e., equal levels
of 9,11 and 10,12 isomers—referred to as a CLA mixture),
when expressed per unit body weight. For example,
most adult human studies provide 3 to 6 g/day of
a CLA mixture, whereas rodent studies provide 0.5% to
1.5% of a CLA mixture (w/w) in the diet. When expressed
per unit of body weight, humans receive approximately
0.05 g CLA/kg body weight, whereas mice received
1.07 g CLA/kg body weight, which is 20 times the human
dose based on body weight. Thus, part of the discrepancy
in results obtained from human and animal studies
is likely due to this large difference in the dose of CLA
administered. Supplementing humans with higher, or animals
with lower, doses of CLA would address this issue.
Other discrepancies in experimental designs include using
CLA isomer mixtures versus single isomers, duration
of CLA supplementation, and the age, weight, gender, and
metabolic status of the subjects or animals.
In vitro studies have been conducted in a variety of cells
types, primarily using an equal mixture of 9,11 and 10,12
CLA, or each isomer individually. Doses used in cell
studies generally range between 1 to 100 M, reflecting
the concentration found in human participants following
supplementation. Results from these studies suggest
that these isomers are readily taken up by cells. For example,
we found that 10,12 CLA is readily incorporated
into neutral and phospholipid fractions of the primary
human adipocyte cultures and reduced lipid and glucose
metabolism (12). Similar to in vivo studies, 9,11 CLA acted
more like the linoleic acid controls.
ANTICANCER PROPERTIES OF CLA
Pariza’s group initially discovered that CLA isomers in
fried ground beef acted as anticarcinogens (13). Subsequently,
numerous investigators have shown that CLA
mixtures or individual isomers decrease tumor cell growth
or increase cancer cell death in in vitro and in vivo models
of mammary, gastric, or skin cancer (reviewed in Ref. 14).
For example, feeding 0.8% to 1.0% individual CLA isomers
or mixtures block the initiation or progression of chemically
induced carcinogenesis in several rodent models
(15–17). A 5 M CLA mixture prevented cell growth and
cytokine production in transformed human keratinocyte like
cells (18). Proposed anticarcinogenic mechanisms
for CLA include decreasing nuclear factor (NF) B and
cyclooxygenase (COX) activity, thereby suppressing the
levels of prostaglandin (PG)E2, an inflammatory PG that
promotes the progression of certain forms of cancer and induces
human epidermal growth factor receptor 2 (HER2)
oncogene expression (19).
CLA Induces Apoptosis of Cancer Cells
Several groups have reported that CLA isomers cause
apoptosis or programmed cell death in cancer cells (reviewed
in Ref. 11). For example, 32 to 128 M CLA mixture
prevented rat mammary cancer cell growth through
apoptosis and decreased DNA synthesis in rat mammary
cancer cells (20). Moreover, 40 to 80 M 10,12 CLA induces
apoptosis in breast cancer cells (19,21,22). Proposed
proapoptotic mechanisms of CLA include inducing atypical
endoplasmic reticulum (ER) stress, leading to caspase-
12 activation (22).
In contrast to the cell and animal studies cited in
the preceding text, a recent prospective cohort study conducted
in Sweden found no evidence to support a protective
effect of CLA consumption on the development
of breast cancer in women (23). Furthermore, some studies
show that 10,12 CLA enhances the risk of developing
certain types of cancer (24). Thus, clinical studies examining
the effects of purified CLA isomers on preventing or
treating cancer, and safety issues, are needed.
ANTIOBESITY ACTIONS OF CLA
Due to the substantial rise in obesity over the past 30 years,
there is a great deal of interest in CLA as a weight loss
treatment, as it has been shown to decrease body weight
and body fat mass (BFM).
Conjugated Linoleic Acid weight loss
supplementation with a CLA mixture (i.e., 10,12 + 9,11 isomers in equal
concentrations) or the 10,12 isomer alone decreases BFM
in many animal and some human studies (reviewed in
Refs. 25 and 26). Of the two major isomers of CLA, the Martinez et al isomer is responsible for the antiobesity properties (27–31).
CLA Decreases Body Weight and Body Fat Mass
Park et al. (32) were one of the first groups to demonstrate
that CLA modulated body composition. Compared
with controls, male and female mice supplemented with a
0.5% (w/w) CLA mixture had 57% and 60% less BFM, respectively.
Since these findings, researchers have demonstrated
that CLA supplementation consistently reduces
BFM in mice, rats, and pigs.
For example, dietary supplementation with 1% (w/w) CLA mixture for 28 days
decreased body weight and periuterine white adipose tissue
(WAT) mass in C57BL/6J mice (36).
In humans, some studies show that CLA decreases
BFM and increases lean body mass (LBM), whereas others
show no such effects. For example, supplementation of 3
to 4 g/day of a CLA mixture for 24 weeks decreased BFM
and increased LBM in overweight and obese people (37).
On the other hand, supplementation of 3.76 g/day of a
CLA mixture in yogurt for 14 weeks in healthy adults had
no effect on body composition (38). Supplementation with
3.2 g/day of aCLAmixture decreased totalBFMand trunk
fat compared with placebo in overweight participants, but
not obese participants (39). These contradictory findings
among human studies may be due to the following differences
in experimental design: (i) mixed versus individual
and (iii) gender, weight, age and metabolic status of the
These antiobesity effects of CLA do not appear to
be solely due to reductions in food intake in animals (40–
42) or humans (43,44). Several mechanisms by which CLA
decreases BFM will now be examined.
CLA Increases LBM
A recent meta-analysis of 18 human, placebo-controlled
fat-free mass (FFM) by 0.3 kg, regardless of the
duration or dose (45). When these same 18 studies were
examined for reductions in BFM, it was shown that CLA
supplementation decreased BFM by 0.05 kg/week for up
to one year (25). The average CLA mixture dose for these
studies was 3.2 g/day. Collectively, these meta-analyses
studies suggest that CLA supplementation of humans results
in a rather small but rapid increase in FFM or LBM,
and a much larger decrease in BFM over an extended period
of time. The effects of CLA on FFM orLBMin humans
mayvary depending on baseline body mass index, gender,
age, and exercise status of the participants.
Two proposed mechanisms by which CLA increases
LBM are via increasing bone or muscle mass. 10,12 CLA
supplementation for 10 weeks with a 0.5% (w/w) CLA
mixture increased bone mineral density (BMD) and muscle
mass in C57BL/6 female mice (46). CLA supplementation
has been proposed to increase BMD via increasing
osteogenic gene expression and decreasing osteoclast activity
(46,47). Furthermore, CLA supplementation alone
or with exercise increased BMD compared with control
mice (48). An alternative mechanism could be that CLA
decreases adipogenesis of pluripotent mesenchymal stem
cells (MSC) in bone marrow, and instead promotes their
commitment to become bone cells. Indeed, 10,12 CLA has
been shown to decrease the differentiation of MSC into
adipocytes and increase calcium deposition and markers
of osteoblasts (49). In contrast, 9,11 CLA increased
adipocyte differentiation and decreased osteoblast differentiation.
Consistent with these in vitro data, CLA mixture
supplementation of rats treated with corticosteroids prevented
reductions in LBM, BMD, and bone mineral content
(50). Increasing LBM is directly linked to an increase
in basal metabolic rate (BMR).
In addition to its effects on BMD, recent evidence
supports a role of CLA in increasing endurance and muscle
strength. For example, maximum swimming time until
fatigue was higher in CLA fed versus control mice
(51). Aging mice supplemented with a CLA mixture and
10,12 CLA had higher muscle weight compared with
isomers increased levels of antioxidant enzyme activity,
ATP, and enhanced mitochondrial potential, indicating a
protective effect against age-associated muscle loss (52).
In humans, CLA increased bench-press strength in men
supplemented with 5 g/day for seven weeks who underwent
resistance training three days per week (53).
Furthermore, supplementation with CLA combined with
creatine monohydrate (C) and whey protein (P) led to
greater increases in bench-press and leg-press strength
than supplementation with C+P or P alone (54). Although
preliminary, these data suggest that CLA may enhance
exercise-induced muscle strength or prevent sarcopenia
or age-related muscle loss.
CLA Increases Energy Expenditure
CLA has been proposed to reduce adiposity by elevating
energy expenditure via increasing BMR, thermogenesis,
or lipid oxidation in animals (27,42,55). In BALB/c male
mice fed mixed isomers of CLA for six weeks, body fat
was decreased by 50% and was accompanied by increased
BMR compared with controls (42). Enhanced thermogenesis
may be associated with increased uncoupling of mitochondria
via uncoupling protein (UCP)s, which facilitate
proton transport over the inner mitochondrial membrane
thereby leading to dissipation of energy as heat instead
of ATP synthesis. UCP1 is highly expressed in brown adipose
tissue (BAT), and in WAT at lower levels. UCP3 is
expressed in muscle and in a number of other tissues,
whereas UCP2 is the form expressed at the highest level
across most tissues. Supplementation with a CLA mixture
or 10,12 CLA in rodents induced UCP2 mRNA expression
in WAT (29,56). Recently, it was demonstrated that CLA
increased mRNA and protein expression of UCP1 inWAT
(57). Similarly, CLA supplementation induced UCP gene
expression and elevated -oxidation in muscle and liver
CLA Increases Fat Oxidation
CLA has been shown to regulate the gene expression
or activity of proteins associated with FA oxidation in
adipose tissue, muscle, and liver. For example, CLA induced
the expression of carnitine palmitoyl transferase 1
(CPT1) in WAT of obese Zucker fa/fa rats (63). Additionally,
10,12 CLA increased the expression of peroxisome
proliferator-activated receptor (PPAR) coactivator-1
Conjugated Linoleic Acid 169
(PGC1) in WAT of mice (57). Consistent with these
in vivo findings, 10,12 CLA increased -oxidation in differentiating
3T3-L1 preadipocytes (64). Furthermore, 10,12
CLA treatment increased AMP kinase (AMPK) activity
and increased phospho-acetyl-CoA carboxylase (ACC)
levels in 3T3-L1 adipocytes, suggesting an increase in FA
oxidation and a decrease in FAesterification to triglyceride
In muscle, 10,12 CLA increased CPT1 expression in
hamsters fed an atherogenic diet (60). Supplementation of
a CLA mixture in high fat fed hamsters led to increased
CPT1 activity in muscle (66). A CLA mixture increased
CPT1b, UCP3, acetyl-CoA oxidase (ACO) 2, and PPAR
mRNA levels in skeletal muscle of Zucker rats (67). Consistent
with these data, 10,12 CLA increased mRNA levels
(63) and activity (68) of CPT1 in the liver. Additionally,
10,12 CLA increased hepatic peroxisomal fatty COactivity
(68), suggesting increased peroxisomal -oxidation in
addition to mitochondrial oxidation. These findings suggest
CLA may reduce adiposity through increased energy
expenditure via increased mitochondrial uncoupling and
FA oxidation in WAT, muscle, and liver.
At least one report demonstrates that CLA increases
FA oxidation in human participants (69). In this study,
overweight adults supplemented with 4 g/day of a CLA
mixture for six months had a lower respiratory quotient
(RQ), indicating an increase in FA oxidation compared
with placebo controls. However, others have shown no
effect of CLA on energy expenditure or fat oxidation in
humans (70,71). These discrepancies may be due to the
length of treatment, time period of measurement, and
time at which measurements are taken. For instance, CLA
treatment for four to eight weeks had no effect on energy
expenditure or FA oxidation, based on a 20-minute measurement
during resting and walking (70). In contrast, the
study by Close et al. (69) administered CLA for six months
and measured FA oxidation over a 24-hour period and
found that CLA increased FA oxidation and energy expenditure.
Thus, discrepancies in this area may be due to
insufficient duration of CLA treatment or measurements
of energy expenditure or FA oxidation.
CLA Decreases Adipocyte Size
Lipolysis is the process by which stored TG is mobilized,
releasing free fatty acids (FFAs) and glycerol for use by
metabolically active tissues. C57BL/6J mice fed 10,12 CLA
for three days had increased mRNA levels of hormone sensitive
lipase (HSL), a key enzyme for TG hydrolysis
(56). Consistent with these data, acute treatment withCLA
mixture or 10,12 CLA alone increased lipolysis in 3T3-L1
(32,72) and newly differentiated human adipocytes (73).
decreased TG content, adipocyte size, and lipid locule size
in adipocytes (74). Similarly, mice fed 1% CLA displayed
increased numbers of small adipocytes with a reduction in
the number of large adipocytes (75). Furthermore, a CLA
mixture reduced adipocyte size rather than cell number
in Sprague Dawley (40) and fa/fa Zucker rats (76). Thus,
CLA may reduce adipocyte size by increasing lipolysis.
CLA Decreases Adipocyte Differentiation
The conversion of preadipocytes to adipocytes involves
the activation of key transcription factors such as
PPAR and CAAT/enhancer-binding proteins (C/EBPs).
There is much evidence showing that CLA suppresses
preadipocyte differentiation in animal (77–79) and human
(12,80) preadipocytes treated with a CLA mixture or 10,12
the expression of PPAR, C/EBP, sterol regulatory
element-binding protein-1c (SREBP-1c), liver X receptor
(LXR), and adipocyte FA-binding protein (aP2),
thereby reducing adipogenesis and lipogenesis (12,29,79).
In rodents, supplementation of 10,12 CLA decreased
the expression of PPAR and its target genes (79,81–83).
In contrast, humans supplemented with a CLA mixture
had higher mRNA levels of PPAR in WAT, but no difference
in body weight or BFM (38). In mature, in vitrodifferentiated
primary human adipocytes or in mature
3T3-L1 adipocytes, 10,12 CLA treatment leads to a substantial
decrease in the expression and activity of PPAR
(82,83), and a decrease in PPAR target genes and lipid
content (80). This shows that 10,12 is not only able to inhibit,
but also to reverse the adipogenic process and indicates
that this may be mediated by suppression of PPAR
activity. In addition to its effect on PPAR, 10,12 CLA may
also directly impact the activity of other transcription factors
involved in adipogenesis and lipogenesis (i.e., LXR,
C/EBPs, SREBP-1c), which could contribute to CLA’s antiobesity
CLA Decreases Glucose and FA Uptake and TG Synthesis
Conversion of glucose and FAs to TG is a major function
of adipocytes. Genes involved in lipogenesis, such
as a LPL, ACC, fatty acid synthase (FAS), and stearoyl-
CoA desaturase (SCD), were decreased following supplementation
alone (12,56,72,80). PPAR is a major activator of many
lipogenic genes including glycerol-3-phosphate dehydrogenase
(GPDH), LPL, and lipin as well as many genes encoding
lipid droplet-associated proteins, such as perilipin,
adipocyte differentiation-related protein (ADRP), and cell
death–inducing DNA fragmentation factor of apoptosislike
effector c (CIDEC) (84). Thus, the antilipogenic action
of 10,12 CLA may be explained by inhibition of PPAR activity.
In addition,CLArepression of expression of SREBP-
1 and its target genes may play an important role in delipidation.
Finally, CLA suppression of insulin signaling may
also impair insulin’s ability to activate or increase the
abundance of a number of lipogenic proteins including
LPL, ACC, FAS, SCD-1, and the insulin-dependent glucose
CLA Decreases Adipocyte Number
Apoptosis is another mechanism by which CLA may reduce
BFM. Apoptosis can occur through activation of the
death receptor pathway, ER stress, or the mitochondrial
pathway. A number of in vivo and in vitro studies have
reported apoptosis in adipocytes supplemented with a
supplementation of C57BL/6J mice with 1% (w/w)
CLA mixture reduced BFM and increased apoptosis in
WAT (75). Mice fed a high-fat diet containing 1.5% (w/w)
CLA mixture had an increased ratio of BAX, an inducer of
apoptosis relative to Bcl2, a suppressor of apoptosis (87).
170 Martinez et al.
Figure 2 Reported mechanisms by which 10,12 CLA decreases adipose
tissue mass and obesity.
Reported mechanisms by which CLA reduces adiposity
are shown in Figure 2.
ANTIDIABETIC PROPERTIES OF CLA
Feeding obese ob/ob C57BL/6 mice 0.6% 9,11 CLA for
six weeks improved plasma levels of glucose, TG, and
insulin and reduced the expression of markers of inflammation
and insulin resistance in WAT (88). Furthermore,
these authors demonstrated that 50 M 9,11 CLA prevented
tumor necrosis factor (TNF)-mediated insulin resistance
in 3T3-L1 murine adipocytes. Their data suggest
that 9,11 CLA improves insulin sensitivity by elevating
GLUT4 levels or translocation to the plasma membrane,
which are adversely affected by inflammation, thereby
facilitating glucose disposal. Similarly, Wistar rats fed a
high-fat diet supplemented with a 0.75% to 3.0% CLA
mixture for 12 weeks had lower plasma levels of glucose,
TG, and insulin compared with high-fat fed control rats
(89). The CLA mixture enhanced the expression of PPAR
target genes in WAT, which was proposed to be responsible
for the improvement in insulin sensitivity. Consistent
with these data, adiponectin, a WAT-specific, PPAR target
gene that reduces blood glucose by enhancing its oxidation
in liver and muscle, was increased in the plasma
of Zucker diabetic fatty (ZDF) rats fed a 1% CLA mixture
for eight weeks (55). Similarly, feeding 0.5% 9,11 CLA to
insulin resistant C57BL/6J mice improved insulin sensitivity
without affecting BFM (90). Conversely, these authors
found that feeding 0.5% 10,12 CLA lowered BFM
and increased LBM in these mice, but caused insulin resistance.
Other studies have also reported that 10,12 CLA
causes insulin resistance, especially in mice (81,99). Taken
together, these data suggest that 9,11 and 10,12 CLA have
opposite effects on insulin sensitivity, most likely due
to their opposing effects on the activity of PPAR, visa-
ANTIATHEROSCLEROTIC ACTIONS OF CLA
CLA has been reported to decrease risk factors of
atherosclerosis in several important animal models (reviewed
in Ref. 91). For example, feeding 0.5% mixed or
individual isomers of CLA to New Zealand White rabbits
fed a high saturated fat and cholesterol-rich diet reduced
blood lipids and atherosclerotic lesion area (92). Syrian
Golden hamsters fed a high saturated fat and cholesterolrich
diet containing 1.0% mixed CLA isomers (93), 0.9%
lipid accumulation or fewer fatty aortic streaks compared
with controls. In apoE−/− deficient mice, feeding a 1.0%
CLA mixture decreased aortic lesion area, and reduced
macrophage infiltration and inflammatory gene expression
in the lesions (96). In contrast to these animal studies,
other animal and clinical trials with CLA mixtures have
yet to show beneficial effects on reducing risk factors for
atherosclerosis (reviewed in Ref. 97).
Adverse side effects have been reported for CLA supplementation
such as elevated levels of inflammatory
markers, lipodystrophy, steatosis, and insulin resistance.
Most adverse side effects are due to the 10,12 CLA
CLA Increases Markers of Inflammation
Treatment with 10,12 CLA increases the expression or
secretion of inflammatory makers such as TNF, interleukin
(IL)-1, IL-6, and IL-8 from adipocyte cultures
(56,73,80,81,83). Moreover, CLA increases the expression
of COX-2, an enzyme involved in the synthesis of PGs,
and the secretion of PGF2 (79,98). These inflammatory
proteins are known to antagonize PPAR activity and insulin
Consistent with these in vitro data, 10,12 CLA
supplementation increases the levels of inflammatory
cytokines and PGs in humans (101,102). For example,
women supplemented with 5.5 g/day of a CLA mixture
for 16 weeks had higher levels of C-reactive protein
in serum and 8-iso-PGF2 in urine (44). 10,12 CLA
supplementation in mice resulted in macrophage recruitment
in WAT (81). In contrast, 9,11 CLA exhibits antiinflammatory
CLA Causes Insulin Resistance
Insulin resistance has been reported in vivo (56,102–104)
and in vitro (12,73,79,98) following supplementation with
CLA supplementation of 3.4 g/day for 12 weeks in obese
men with metabolic syndrome increased serum glucose
and insulin levels and decreased insulin sensitivity (103).
Supplementation with a CLA mixture in type-2 diabetics
increased fasting plasma glucose levels and reduced
insulin sensitivity (102). Mice fed 1% (w/w) 10,12 CLA
displayed elevated fasted and feeding plasma insulin
levels and had reduced insulin sensitivity (75). Consistent
with these data, the mRNA levels of adiponectin,
a key adipokine associated with insulin sensitivity, decrease
following supplementation with 10,12 CLA in vivo
(36,81,100) and in vitro (79,82,105,106).
CLA Causes Lipodystrophy
The combination of inflammation and insulin resistance
results in reduced FA and glucose uptake in WAT,
leading to ectopic lipid accumulation in the blood (hyperlipidemia),
liver (steatosis), or muscle. CLA-mediated
hyperlipidemia and steatosis has been reported in several
animal studies (36,76,107). For example, 1% (w/w)
CLA time-dependently increased insulin levels and led
Conjugated Linoleic Acid 171
Figure 3 Reported mechanisms by which CLA reduces the risk of cancer,
obesity, diabetes, and atherosclerosis.
to increased liver weight and liver lipid accumulation in
C57BL/6J mice (36). Aging C57BL/6J mice fed 0.5% 10,12
CLA displayed increased insulin resistance and liver hypertrophy
US Regulatory Status
Recently, the FDA approved CLA as GRAS (generally recognized
as safe) for use in foods and beverages (not to
exceed 1.5 g/serving) due its potential favorable effects.
However, the use ofCLAas a dietary supplement or ingredient
should be cautioned based on the aforementioned
There is an abundance of evidence in animals suggesting
that CLA consumption may reduce the incidence or risk
of developing cancer, obesity, diabetes, or atherosclerosis,
depending on the type and abundance of CLAisomer consumed
and the physiological status of the animal model
(Fig. 3). Data on the antiobesity properties of 10,12 CLA
in animals, especially mice, are the most reproducible.
However, these potential benefits are not without risks,
as the 10,12 isomer is associated with increased levels of
inflammatory markers, lipodystrophy, and insulin resistance.
More clinical studies are needed to determine the
efficacy of CLA isomers in humans, and more mechanistic
animal and cell studies are needed to determine the precise,
isomer-specific mechanisms of action of CLA, and
potential side effects.
This work was supported by NIH NIDDK R15 DK 059289,
NIH NIDDK/ODS R01DK063070, USDA-NRI 199903513,
and NCARS 06771 awards to Michael McIntosh, NRSA
NIH Fellowships to Kristina Martinez (F31DK084812)
and Arion Kennedy (F31DK076208), and a United Negro
College Fund-Merck predoctoral Fellowship to Arion
synthesized endogenously in lactating dairy cows by delta-
9 desaturase. J Nutr 2000; 130(9):2285–2291.
linoleic acid contents of dairy products. J Dairy Sci 1995;
dienoic isomers of linoleic acid, a newly recognized
class of anticarcinogens. J Food Comp Anal 1992; 5:185–197.
acid (CLA) in German foods and evaluation of daily intake.
Z Lebensum Unters Forsch A 1998; 206:77–82.
linoleic acids are synthesized via different mechanisms
in ruminal digesta and bacteria. J Lipid Res 2007;
linoleic acid-enriched beef diet attenuates
lipopolysaccharide-induced inflammation in mice in part
through PPARg-mediated suppression of toll-like receptor
4. J Nutr 2009; 139(12):2351–2357.
7. Bell J, Griinari J, Kennelly J. 2006. Effect of safflower oil,
flaxseed oil, monensin, and vitamin E on concentration of
conjugated linoleic acid in bovine milk fat. J Dairy Sci 2006;
8. Pariza MW, Park Y, Cook ME. The biologically active isomers
of conjugated linoleic acid. Prog Lipid Res 2001;
9. Ritzenthaler KL, McGuire MK, Falen R, et al. Estimation
of conjugated linoleic acid intake by written dietary
assessment methodologies underestimates actual intake
evaluated by food duplicate methodology. J Nutr 2001;
10. Mougios V, Matsakas A, Petridou A, et al. Effect of supplementation
with conjugated linoleic acid on human serum
lipids and body fat. J Nutr Biochem 2001; 12(10):585–594.
11. Petridou A, Mougios V, Sagredos A. Supplementation with
CLA: Isomer incorporation into serum lipids and effect on
body fat of women. Lipids 2003; 38(8):805–811.
12. Brown M, Sandberg-Boysen M, Skov S, et al. Isomer-specific
regulation of metabolism and PPAR by conjugated linoleic
acid (CLA) in human preadipocytes. J Lipid Res 2003;
13. Ha YL, Grimm NK, ParizaMW. Anticarcinogens from fried
ground beef: Heat-altered derivatives of linoleic acid. Carcinogenesis
14. Kelley NR, Hubbard NE, Erickson KL. Conjugated linoleic
acid isomers and cancer. J Nutr 2007; 137(12):2599–2607.
15. Thompson H, Zhu Z, Banni S, et al. Morphological and
biochemical status of the mammary gland as influenced
by conjugated linoleic acid: Implication for a reduction
in mammary cancer risk. Cancer Res 1997; 57(22):5067–
16. Ip C, Banni S, Angioni E, et al. Conjugated linoleic acidenriched
butter fat alters mammary gland morphogenesis
and reduces cancer risk in rats. J Nutr 1999; 129(12):2135–
17. Ip MM, Masso-Welch PA, Ip C. Prevention of mammary
cancer with conjugated linoleic acid: Role of the stroma
and the epithelium. J Mammary Gland Biol Neoplasia 2003;
18. Martinasso G, Sarcino S, Maggiora M, et al. Conjugated
linoleic acid prevents cell growth and cytokine production
induced by TPA in human keratinocytes NCTC 2544. Cancer
Lett 2010; 287(1):62–66.
19. Flowers M, Thompson PA. t10,c12 conjugated linoleic acid
suppresses HER2 protein and enhances apoptosis in SKBr3
172 Martinez et al.
breast cancer cells: Possible role of COX2. PLoS One 2009;
20. Ip MM, Masso-Welch PA, Shoemaker SF, et al. Conjugated
linoleic acid inhibits proliferation and induces apoptosis of
normal rat mammary epithelial cells in primary culture.
Exp Cell Res 1999; 250(1):22–34.
21. Wang L, HuangYW, Yan P, et al. Conjugated linoleic acid induces
apoptosis through estrogen receptor alpha in human
breast tissue. BMC Cancer 2008; 8:208–222.
22. Ou L,Wu Y, Ip C, et al. Apoptosis induced by t10,c12 conjugated
linoleic acid is mediated by an atypical endoplasmic
reticulum stress response. J Lipid Res 2008; 49(5):985–994.
23. Larsson S, Bergkvist L, Wolk, A. Conjugated linoleic acid
intake and breast cancer risk in a prospective cohort study
of Swedish women. Am J Clin Nutr 2009; 90(3):556–560.
24. Meng X, Shoemaker S, McGee S, et al. t10,c12 conjugated
linoleic acid stimulates mammary tumor progression in
Her2/ErbB2 mice through activation of both proliferation
and survival pathways. Carcinogenesis 2008; 29(5):1013–
25. Whigham LD, Watras AC, Schoeller DA. Efficacy of conjugated
linoleic acid for reducing fat mass: A meta-analysis
in humans. Am J Clin Nutr 2007; 85(5):1203–1211.
26. Wang YW, Jones PJ. Conjugated linoleic acid and obesity
control: Efficacy and mechanisms. Int J Obes Relat Metab
Disord 2004; 28(8):941–955.
27. Park Y, Storkson J, Albright K, et al. Evidence that trans-
10, cis-12 isomer of conjugated linoleic acid induces body
composition changes in mice. Lipids 1999; 34(3):235–241.
28. Brown JM, Halverson YD, Lea-Currie R, et al. Trans-10,
cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates
lipogenesis in primary cultures of stromal vascular
cells from human adipose tissue. J Nutr 2001; 131(9):2316–
29. House RL, Cassady JP, Eisen EJ, et al. Functional genomic
characterization of delipidation elicited by trans-10, cis-12-
conjugated linoleic acid (t10c12-CLA) in a polygenic obese
line of mice. Physiol Genomics 2005; 21(3):351–361.
30. Brandebourg TD, Hu CY. Isomer-specific regulation of differentiating
pig preadipocytes by conjugated linoleic acids.
J Anim Sci 2005; 83(9):2096–2105.
31. Raff M, Tholstrup T, Toiubro S, et al. Conjugated linoleic
acids reduce body fat in healthy postmenopausal women. J
Nutr 2009; 139(7):1347–1352.
32. Park Y, Albright KJ, LiuW, et al. Effect of conjugated linoleic
acid on body composition in mice. Lipids 1997; 32(8):853–
33. Sisk MB, Hausman DB, Martin RJ, et al. Dietary conjugated
linoleic acid reduces adiposity in lean but not obese Zucker
rats. J Nutr 2001; 131(6):1668–1674.
34. Cl´ement L, Poirier H, Niot I, et al. Dietary trans-10, cis-12
conjugated linoleic acid induces hyperinsulinemia and fatty
liver in the mouse. J Lipid Res 2002; 43(9):1400–1409.
35. Meadus WJ, MacInnis R, Dugan, M. Prolonged dietary
treatment with conjugated linoleic acid stimulates porcine
muscle peroxisome proliferator activated receptor gamma
and glutamine–fructose aminotransferase gene expression
in vivo. J Mol Endocrinol 2002; 28(2):79–86.
36. Poirier H, Rouault C, Cl´ement L, et al. Hyperinsulinemia
triggered by dietary conjugated linoleic acid is associated
with a decrease in leptin and adiponectin plasma levels and
pancreatic beta cell hyperplasia in the mouse. Diabetologia
37. Gaullier JM, Halse J, Høivik HO, et al. Six months supplementation
with conjugated linoleic acid induces regionalspecific
fat mass decreases in overweight and obese. Br J
Nutr 2007; 97(3):550–560.
38. Nazare JA, de la Perri`ere AB, Bonnet F, et al. Daily intake
of conjugated linoleic acid-enriched yoghurts: effects on
energy metabolism and adipose tissue gene expression in
healthy subjects. Br J Nutr 2007; 97(2):273–280.
39. Laso N, Brugu´e E, Vidal J, et al. Effects of milk supplementation
with conjugated linoleic acid (isomers cis-9, trans-11
and trans-10, cis-12) on body composition and metabolic
syndrome components. Br J Nutr 2007; 98:860–867.
40. Azain MJ, Hausman DB, Sisk MB, et al. Dietary conjugated
linoleic acid reduces rat adipose tissue cell size rather than
cell number. J Nutr 2000; 130:1548–1554.
41. West DB, Blohm FY, Truett AA, et al. Conjugated linoleic
acid persistently increases total energy expenditure in
AKR/J mice without increasing uncoupling protein gene
expression. J Nutr 2000; 130:2471–2477.
42. Terpstra AH, Javadi M, Beynen AC, et al. Dietary conjugated
linoleic acids as free fatty acids and triacylglycerols
similarly affect body composition and energy balance in
mice. J Nutr 2003; 133:3181–3186.
43. Lambert EV, Goedecke JH, Bluett K, et al. Conjugated
linoleic acid versus high-oleic acid sunflower oil: Effects
on energy metabolism, glucose tolerance, blood lipids, appetite
and body composition in regularly exercising individuals.
Br J Nutr 2007; 97:1001–1011.
44. Tholstrup T, RaffM, Straarup EM, et al. An oil mixture with
trans-10, cis-12 conjugated linoleic acid increases markers of
inflammation and in vivo lipid peroxidation compared with
cis-9, trans-11 conjugated linoleic acid in postmenopausal
women. J Nutr 2008; 138:1445–1451.
45. Schoeller DA, Watras AC, Whigham LD. A meta-analysis
of the effects of conjugated linoleic acid on fat-free mass in
humans. Appl Physiol Nutr Metab 2009; 34:975–978.
46. Rahman MM, Bhattacharya A, Banu J, et al. Conjugated
linoleic acid protects against age-associated bone loss in
C57BL/6 female mice. J Nutr Biochem 2007; 18:467–474.
47. Banu J, Bhattacharya A, Rahman M, et al. Effects of conjugated
linoleic acid and exercise on bone mass in young
male Balb/C mice. Lipids Health Dis 2006; 5:7.
48. Banu J, Bhattacharya A, Rahman M, et al. Beneficial effects
of conjugated linoleic acid and exercise on bone of middleaged
female mice. J Bone Miner Metab 2008; 26:436–445.
49. Platt ID, El-Sohemy A. Regulation of osteoblast and
adipocyte differentiation from human mesenchymal stem
cells by conjugated linoleic acid. J Nutr Biochem 2009;
50. Roy BD, Bourgeois J, Rodriguez C, et al. Conjugated linoleic
acid prevents growth attenuation induced by corticosteroid
administration and increases bone mineral content in young
rats. Appl Physiol Nutr Metab 2008; 33:1096–1104.
51. Mizunova W, Haramizu S, Shibakusa T, et al. Dietary conjugated
linoleic acid increases endurance capacity and fat
oxidation in mice during exercise. Lipids 2005; 40(3):265–
52. Rahman MM, Halade G, Jamali AE, et al. Conjugated
linoleic acid (CLA) prevents age-associated skeletal muscle
loss. BBRC 2005; 383:513–518.
53. Pinkoski C, Chilibeck PD, Candow DG, et al. The effects of
conjugated linoleic acid supplementation during resistance
training. Med Sci Sports Exerc 2006; 38(2):339–348.
54. Cornish SM, Candow DG, Jantz NT, et al. Conjugated
linoleic acid combined with creatine monohydrate and
whey protein supplementation during strength training. Int
J Sport Nutr Exerc Metab 2009; 19(1):79–96.
55. Nagao K, Inoue N,Wang YM, et al. Conjugated linoleic acid
enhances plasma adiponectin level and alleviates hyperinsulinemia
and hypertension in Zucker diabetic fatty (fa/fa)
rats. Biochem Biophys Res Commun 2003; 310(2):562–566.
56. LaRosa PC, Miner J, Xia Y, et al. Trans-10, cis-12 conjugated
linoleic acid causes inflammation and delipidation of white
adipose tissue in mice: A microarray and histological analysis.
Physiol Genomics 2006; 27:282–294.
Conjugated Linoleic Acid 173
57. Wendel AA, Purushotham A, Liu LF, et al. Conjugated
linoleic acid induces upcoupling protein 1 in white adipose
tissue of ob/ob mice. Lipids 2009, 44(11):975–982.
58. Roche HM, Noone E, Sewter C, et al. Isomer-dependent
metabolic effects of conjugated linoleic acid: Insights
from molecular markers sterol regulatory elementbinding
protein-1c and LXRalpha. Diabetes 2002; 51:2037–
59. Choi JS, Koh IU, Jung MH, et al. Effects of three different
conjugated linoleic acid preparations on insulin signaling,
fat oxidation and mitochondrial function in rats fed a highfat
diet. Br J Nutr 2007; 98:264–275.
60. Ribot J, Portillo MP, Pic´o C, et al. Effects of trans-10, cis-12
conjugated linoleic acid on the expression of uncoupling
proteins in hamsters fed an atherogenic diet. Br J Nutr 2007;
61. Priore P, Giudetti AM, Natali F, et al. Metabolism and shortterm
metabolic effects of conjugated linoleic acids in rat
hepatocytes. Biochim Biophys Acta 2007; 1771:1299–1307.
62. Ferramosca A, Savy V, Conte L, et al. Dietary combination
of conjugated linoleic acid (CLA) and pine nut oil prevents
CLA-induced fatty liver in mice. J Agric Food Chem 2008;
63. Gudbrandsen OA, Rodr´ıguez E, Wergedahl H, et al. Trans-
10, cis-12-conjugated linoleic acid reduces the hepatic triacylglycerol
content and the leptin mRNA level in adipose
tissue in obese Zucker fa/fa rats. Br J Nutr 2009; 102:803–
64. Evans M, Geigerman C, Cook J, et al. Conjugated linoleic
acid suppresses triglyceride accumulation and induces
apoptosis in 3T3-L1 preadipocytes. Lipids 2000; 35:899–910.
65. Jiang S, Wang Z, Riethoven JJ, et al. Conjugated linoleic
acid activates AMP-activated protein kinase and reduces
adiposity more effectively when used with metformin in
mice. J Nutr 2009; 139(12):2244–2251.
66. Zabala A, Fernandez-Quintela A, Macarulla MT, et al. Effects
of conjugated linoleic acid on skeletal muscle triacylglycerol
metabolism in hamsters. Nutrition 2006; 22:528–
67. Inque N, Nagao K,Wang Y, et al. Dietary conjugated linoleic
acid lowered tumor necrosis factor- content and altered
expression of genes related to lipid metabolism and insulin
sensitivity in the skeletal muscle of zucker rats. J Agric Food
Chem 2006; 54:7935–7939.
68. Macarulla MT, Fern´andez-Quintela A, Zabala A, et al. Effects
of conjugated linoleic acid on liver composition and
fatty acid oxidation are isomer-dependent in hamster. Nutrition
69. Close RN, Schoeller DA, Watras AC, et al. Conjugated
linoleic acid supplementation alters the 6-mo change in fat
oxidation during sleep. Am J Clin Nutr 2007; 86:797–804.
70. Zambell KL, Keim NL, Van Loan MD, et al. Conjugated
linoleic acid supplementation in humans: Effects on
body composition and energy expenditure. Lipids 2000;
71. Kamphius MM, Lejeune MP, Saris WH, et al. The effect
of conjugated linoleic acid supplementation after weight
loss on body weight regain, body composition, and resting
metabolic rate in overweight subjects. Int J Obes Relat
Metab Disord 2003; 27:840–847.
72. Evans M, Lin X, Odle J, et al. Trans-10, cis-12 conjugated
linoleic acid increases fatty acid oxidation in 3T3-L1
preadipocytes. J Nutr 2002; 132:450–455.
73. Chung, S, Brown JM, McIntosh M. Trans-10, cis-12 CLA
increases adipocyte lipolysis and alters lipid dropletassociated
proteins: Role of mTOR and ERK signaling. J
Lipid Res 2005; 46:885–895.
74. Brown M, Evans M, McIntosh M. Linoleic acid partially
restores the triglyceride content of conjugated linoleic acidtreated
cultures of 3T3-L1 preadipocytes. J Nutr Biochem
75. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, et al.
Conjugated linoleic acid supplementation reduces adipose
tissue by apoptosis and develops lipodystrophy in mice.
Diabetes 2000; 49:1534–1542.
76. Noto A, Zahradka P, Yurkova N, et al. Dietary conjugated
linoleic acid decreases adipocyte size and favorably
modifies adipokine status and insulin sensitivity in
obese, insulin-resistant rats. Metabolism 2007; 56:1601–
77. Brodie AE, Manning VA, Ferguson KR, et al. Conjugated
linoleic acid inhibits differentiation of pre- and post- confluent
3T3-L1 preadipocytes but inhibits cell proliferation
only in preconfluent cells. J Nutr 1999; 129:602–606.
78. Choi Y, Kim YC, Han YB, et al. The trans-10,cis-12 isomer of
conjugated linoleic acid downregulates stearoyl-CoA desaturase
1 gene expression in 3T3-L1 adipocytes. J Nutr 2000;
79. Kang K, Liu W, Albright KJ, et al. Trans-10, cis-12 CLA
inhibits differentiation of 3T3-L1 adipocytes and decreases
PPAR gamma expression. Biochem Biophys Res Commun
80. Brown J, Boysen M, Chung S, et al. Conjugated linoleic
acid (CLA) induces human adipocyte delipidation: Autocrine/
paracrine regulation of MEK/ERK signaling by
adipocytokines. J Biol Chem 2004; 279:26735–26747.
81. Poirier H, Shapiro JS, Kim RJ, et al. Nutritional supplementation
with trans-10, cis-12 conjugated linoleic acid induces
inflammation of white adipose tissue. Diabetes 2006;
82. Miller JR, Siripurkpong P, Hawes J, et al. The trans-10, cis-
12 isomer of conjugated linoleic acid decreases adiponectin
assembly by PPARgamma-dependent and PPARgammaindependent
mechanisms. J Lipid Res 2008; 49:550–562.
83. Kennedy A, Chung S, LaPoint K, et al. Trans-10, cis-
12 conjugated linoleic acid antagonizes ligand-dependent
PPARgamma activity in primary cultures of human
adipocytes. J Nutr 2008; 138:455–461.
84. Neilson R, Pedersen T, Hagenbeek D, et al. Genome-wide
profiling of PPARgamma: RXR and RNA polymerase II occupancy
reveals temporal activation of distinct metabolic
pathways and changes in RXR dimer composition during
adipogenesis. Genes Dev 2008; 22:2953–2967.
85. Miner JL, Cederberg CA, Nielsen MK, et al. Conjugated
linoleic acid (CLA), body fat, and apoptosis. Obes Res 2001;
86. Hargrave KM, Li C, Meyer BJ, et al. Adipose depletion and
apoptosis induced by trans-10, cis-12 conjugated linoleic
Acid in mice. Obes Res 2002; 10:1284–1290.
87. Liu LF, Purushotham A, Wendel AA, et al. Combined effects
of rosiglitazone and conjugated linoleic acid on adiposity,
insulin sensitivity, and hepatic steatosis in high-fatfed
mice. Am J Physiol Gastrointest Liver Physiol 2007;
88. Moloney F, Toomey S, Loscher C, et al. Anti-diabetic effect of
cis-9, trans-11 conjugated linoleic acid may be mediated via
anti-inflammatory effects in white adipose tissue. Diabetes
89. Zhou X, Sun C, Liu J, et al. Dietary conjugated linoleic acid
increases PPAR gene expression in adipose tissue of obese
rat, and improves insulin resistance. Growth Horm IGF Res
90. Halade G, Rahman M, Fernandez G. Differential effects of
conjugated linoleic acid isomers in insulin-resistant female
C57Bl/6J mice. J Nutr Biochem 2009, 21(4):332–337.
91. Mitchell P, McLeod R. Conjugated linoleic acid and
atherosclerosis: Studies in animal models. Biochem Cell Biol
174 Martinez et al.
92. Kritchevsky D, Tepper SA, Wright S, et al. Conjugated
linoleic acid isomer effects in atherosclerosis:
Growth and regression of lesions. Lipids 2004; 38:611–
93. Valeille K, Ferezou J, Amsler G, et al. A cis-9, trans-11
conjugated linoleic acid-rich diet reduces the outcome of
atherogenic process in hyperlipidemic hamster. AmJ Physiol
Heart Circ Physiol 2005; 289:H652–659.
94. Valeille K, Ferezou J, Parquet M, et al. The natural concentration
of the conjugated linoleic acid cis-9, trans-11 in milk
fat has antiatherogenic effects in hyperlipidemic hamsters.
J Nutr 2006; 136:1305–1310.
95. Ledoux M, Laoux L, Fountaine J, et al. Rumenic acid
significantly reduces plasma levels of LDL and small
dense LDL cholesterol in hamsters fed a cholesteroland
lipid-enriched semi-purified diet. Lipids 2007; 42:135–
96. Toomey S, Harhen B, Roche H, et al. Profound resolutions
of early atherosclerosis with conjugated linoleic acid.
Atherosclerosis 2006; 187:40–49.
97. Nakamura Y, Flintoff-Dye N, Omaye ST. Conjugated
linoleic acid modulation of risk factors associated with
atherosclerosis. Nutr Metab 2008; 5:22.
98. Kennedy A, Overman A, LaPoint K, et al. Conjugated
linoleic acid-mediated inflammation and insulin resistance
in human adipocytes are attenuated by resveratrol. J Lipid
Res 2009; 50:225–232.
99. Purushotham A, Wendel AA, Liu L, et al. Maintenance of
adiponectin attenuates insulin resistance induced by dietary
conjugated linoleic acid in mice. J Lipid Res 2007;
100. Liu LF, Clipstone, N. Prostaglandin F2alpha inhibits
adipocyte differentiation via a Gq-calcium-calcineurindependent
signaling pathway. J Cell Biochem 2007; 100:161–
101. Steck SE, Chalecki AM, Miller P, et al. Conjugated linoleic
acid supplementation for twelve weeks increases lean body
mass in obese humans. J Nutr 2007; 137:1188–1193.
102. Moloney F, Yeow TP, Mullen A, et al. Conjugated linoleic
acid supplementation, insulin sensitivity, and lipoprotein
metabolism in patients with type 2 diabetes mellitus. Am J
Clin Nutr 2004; 80:887–895.
trans10cis12 conjugated linoleic acid causes isomer-specific
insulin resistance in obese men with the metabolic syndrome.
Diabetes Care 2002; 25:1516–1521.
104. Thrush AB, Chabowski, A, Heigenhauser GJ, et al. Conjugated
linoleic acid increases skeletal muscle ceramide content
and decreases insulin sensitivity in overweight, nondiabetic
humans. Appl Physiol Nutr Metab 2007; 32:372–
105. AhnIS, Choi BH,HaJH, et al. Isomer-specific effect of conjugated
linoleic acid on inflammatory adipokines associated
with fat accumulation in 3T3-L1 adipocytes. J Med Food
106. P´erez-Matute P, Marti A, Mart´ınez JA, et al. Conjugated
linoleic acid inhibits glucose metabolism, leptin and
adiponectin secretion in primary cultured rat adipocytes.
Mol Cell Endocrinol 2007; 268:50–58.
and their mixture on aging C57BL/6J mice. Eur J Nutr