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Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling
lipid metabolism in adipose and liver tissue.
Dietary conjugated linoleic acid increases endurance capacity and fat oxidation in mice
during exercise
Role of the conjugated linoleic acid in the prevention of cancer
Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human
HepG2 liver cells
Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces
body fat mass in healthy, overweight humans
Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated
proteins: role of mTOR and ERK signaling
Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic
enzymes and gene expression in liver and adipose tissue
Isomers of conjugated linoleic acid decrease plasma lipids and stimulate adipose tissue
lipogenesis without changing adipose weight in post-prandial adult sedentary or trained
Wistar rat
Prolonged feeding of mice with conjugated linoleic acid increases hepatic fatty acid synthesis
relative to oxidation
Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy
overweight humans
Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans
Influence of conjugated linoleic acid on body composition and target gene expression in
peroxisome proliferator-activated receptor alpha-null mice
Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity
Efficacy and safety of dietary supplements containing conjugated linoleic acid (CLA) for the treatment of
obesity-evidence from animal and human studies
Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action.
Conjugated linoleic acid (CLA), body fat, and apoptosis
Obes Rev. 2005 Aug;6(3):247-58.
Related Articles, Links
Conjugated linoleic acid evokes de-lipidation through the regulation
of genes controlling lipid metabolism in adipose and liver tissue.
House RL, Cassady JP, Eisen EJ, McIntosh MK, Odle J.
Department of Animal Science & Functional Genomics Program, North Carolina State University,
Raleigh, NC 27695, USA.
Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in
several animal models when included at < or = 1% of the diet. Despite a flurry of investigations,
the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose
tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological
modifications imparted by conjugated linoleic acid on protein and gene expression suggest that
conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure,
apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The
purpose of this review shall be to examine the recent advances and insights into conjugated
linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene
expression and physiology of liver and adipose tissue.
PMID: 16045640 [PubMed - in process]
Lipids. 2005 Mar;40(3):265-71.
Related Articles, Links
Dietary conjugated linoleic acid increases endurance capacity and
fat oxidation in mice during exercise.
Mizunoya W, Haramizu S, Shibakusa T, Okabe Y, Fushiki T.
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School
of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Ingestion of CLA activates beta-oxidation and causes loss of body fat in rodents. We investigated
the effects of dietary CLA on endurance capacity and energy metabolism during exercise in mice.
Five-week-old male BALB/c mice were fed a control diet containing 1.0% linoleic acid or a diet
containing 0.5% CLA that replaced an equivalent amount of linoleic acid for 1 wk. The maximum
swimming time until fatigue was significantly higher in the CLA-fed group than in the control
group. During treadmill running, the respiratory exchange ratio was significantly lower in the
CLA-fed group, but oxygen consumption did not differ significantly between groups, suggesting
that FA contributed more as an energy substrate in the CLA-fed mice. The muscle lipoprotein
lipase activity was significantly higher in the CLA-fed group than in the control group. These
results suggest that CLA ingestion increases endurance exercise capacity by promoting fat
oxidation during exercise.
PMID: 15957252 [PubMed - in process]
Crit Rev Food Sci Nutr. 2005;45(2):135-44.
Related Articles, Links
Role of the conjugated linoleic acid in the prevention of cancer.
Lee KW, Lee HJ, Cho HY, Kim YJ.
Department of Food Science and Technology, School of Agricultural Biotechnology, Seoul
National University, Seoul 151-742, Korea.
There are multiple lines of evidence that a variety of natural fatty acids are effective in health
promotion. Among these fatty acids, conjugated linoleic acid (CLA)--a collective term referring to
a mixture of positional and geometric isomers of linoleic acid (LA, cis-9, cis-12-octadecadienoic
acid)--is currently under intensive investigation due to its health-promotion potential. The
antitumor activity of CLA is of special interest, since it shows inhibitory effects against multistage
carcinogenesis at relatively low dietary levels. Many studies using in vivo and in vitro models
have shown that CLA suppresses the development of multistage carcinogenesis at different sites.
The research to date on CLA has provided a vast amount of information about the mechanism on
how CLA functions in the prevention of cancer. This article discusses characteristics of CLA in
the prevention of cancer in both in vivo and in vitro studies and the possible underlying
chemoprevention mechanisms.
PMID: 15941017 [PubMed - in process]
Clin Chem Lab Med. 2005;43(3):269-74.
Related Articles, Links
Conjugated linoleic acid suppresses the secretion of atherogenic
lipoproteins from human HepG2 liver cells.
Pal S, Takechi R, Ho SS.
Department of Nutrition, Dietetics and Food Science, Curtin University of Technology, Perth,
Western Australia, Australia. [email protected]
Studies in healthy humans have shown that consumption of conjugated linoleic acid (CLA)
significantly reduced very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL)
blood concentrations. We propose that decreased concentrations are due to the inhibition of VLDL
production and secretion [measured by apolipoprotein B100 (apoB100)] from the liver. To
investigate the effects of a mixture of CLA isomers on VLDL metabolism, HepG2 liver cells were
incubated for 24 h with 50 micromol/L of the different fatty acids. Effects of CLA were compared
to a saturated fatty acid (palmitic acid), an n-6 fatty acid (linoleic acid) and no treatment (control).
HepG2-cell apoB100 levels were measured using Western blotting. ApoB100 secretion was
significantly decreased in cells treated with CLA (44%, p<0.005) compared to control cells and
those enriched with palmitic acid. Treatment of cells with CLA also decreased intracellular
cholesterol levels. Collectively, these results demonstrate that CLA reduces apoB100 production
and secretion compared to saturated and polyunsaturated fatty acids, possibly by limiting the
availability of free cholesterol (required for apoB100 production). A reduction in apoB100
production in the body would decrease the levels of VLDL and atherogenic LDL and thus reduce
the risk of developing cardiovascular disease.
J Nutr. 2005 Apr;135(4):778-84.
Related Articles, Links
Supplementation with conjugated linoleic acid for 24 months is well
tolerated by and reduces body fat mass in healthy, overweight
humans.
Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O.
Scandinavian Clinical Research AS, NO-2027 Kjeller, Norway. [email protected]
After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid
(CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid,
and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study
were included in an open study for another 12 mo. The goals of the extension study were to
evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess
the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone
mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d
in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There
was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino
transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced,
whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared
with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered
the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or
body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and
BMM were not affected in any of the groups. Changes in body composition were not related to
diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in
healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in
overweight humans, and may help maintain initial reductions in BFM and weight in the long term.
Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 15795434 [PubMed - indexed for MEDLINE]
J Lipid Res. 2005 May;46(5):885-95. Epub 2005 Feb 16.
Related Articles, Links
Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid
droplet-associated proteins: role of mTOR and ERK signaling.
Chung S, Brown JM, Sandberg MB, McIntosh M.
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 274026170, USA.
Lipid droplet-associated proteins play an important role in adipocyte triglyceride (TG)
metabolism. Here, we show that trans-10,cis-12 conjugated linoleic acid (CLA), but not cis9,trans-11 CLA, increased lipolysis and altered human adipocyte lipid droplet morphology. Before
this change in morphology, there was a rapid trans-10,cis-12 CLA-induced increase in the
accumulation of perilipin A in the cytosol, followed by the disappearance of perilipin A protein. In
contrast, protein levels of adipose differentiation-related protein (ADRP) were increased in
cultures treated with trans-10,cis-12 CLA. Immunostaining revealed that ADRP localized to the
surface of small lipid droplets, displacing perilipin. Intriguingly, trans-10,cis-12 CLA increased
ADRP protein expression to a much greater extent than ADRP mRNA without affecting stability,
suggesting translational control of ADRP. To this end, we found that trans-10,cis-12 CLA
increased activation of the mammalian target of rapamycin/p70 S6 ribosomal protein kinase/S6
ribosomal protein (mTOR/p70S6K/S6) pathway. Collectively, these data demonstrate that the
trans-10,cis-12 CLA-mediated reduction of human adipocyte TG content is associated with the
differential localization and expression of lipid droplet-associated proteins. This process involves
both the translational control of ADRP through the activation of mTOR/p70S6K/S6 signaling and
transcriptional control of perilipin A.
PMID: 15716587 [PubMed - in process]
Diabetes. 2005 Feb;54(2):412-23.
Related Articles, Links
Interaction of fish oil and conjugated linoleic acid in affecting
hepatic activity of lipogenic enzymes and gene expression in liver
and adipose tissue.
Ide T.
Laboratory of Nutritional Biochemistry, National Food Research Institute, 2-1-12 Kannondai,
Tsukuba Science City 305-8642, Japan. [email protected]
The interaction of dietary fish oil and conjugated linoleic acid (CLA) in affecting the activity of
hepatic lipogenic enzymes and gene expression in liver and adipose tissue was examined in mice.
A diet containing 1.0% CLA, mainly composed of 9cis,11trans- and 10trans,12cis-
octadecadienoic acids at equivalent amounts, greatly decreased adipose tissue weight and serum
concentrations of leptin and adiponectin and was accompanied by a downregulation of the
expression of various adipocyte-abundant genes in epididymal adipose tissue. However, CLA
increased the serum insulin concentration fourfold, and it caused hepatomegaly, with huge
increases in the triacylglycerol level and the activity and mRNA levels of hepatic lipogenic
enzymes. Different amounts (1.5, 3, and 6%) of fish oil added to CLA-containing diets dosedependently downregulated parameters of lipogenesis and were accompanied by a parallel
decrease in the triacylglycerol level in the liver. The supplementation of CLA-containing diets
with fish oil was also associated with an increase in fat pad mass and mRNA levels of many
adipocyte-abundant genes in epididymal adipose tissue along with a normalization of serum
concentrations of leptin and adiponectin in a dose-dependent manner. However, in mice fed a diet
containing 1.5% fish oil and CLA in whom fat pad mass was still low and comparable to that in
the animals fed CLA alone, the serum insulin concentration greatly exceeded (twofold) the value
observed in mice fed CLA alone, indicating an aggravation of insulin resistance. This
hyperinsulinemia was ameliorated with increasing amounts of fish oil in the diets. Apparently,
many of the physiological effects of CLA can be reversed by fish oil.
PMID: 15677499 [PubMed - indexed for MEDLINE]
J Nutr Biochem. 2004 Dec;15(12):741-8.
Related Articles, Links
Isomers of conjugated linoleic acid decrease plasma lipids and
stimulate adipose tissue lipogenesis without changing adipose weight
in post-prandial adult sedentary or trained Wistar rat.
Faulconnier Y, Arnal MA, Patureau Mirand P, Chardigny JM, Chilliard Y.
Herbivore Research Unit, Adipose Tissue and Milk Lipids Group, National Institute for
Agricultural Research-Theix, 63122 Saint-Genes Champanelle, France.
The respective effects and interactions of supplementation with two conjugated linoleic acid
(CLA) isomers and exercise on plasma metabolic profile, activity of lipogenic enzymes and
cellularity in two adipose tissue sites, those of the liver and heart, were examined in adult Wistar
rats. Rats that were either sedentary or exercise-trained by treadmill running were fed one of four
diets: a diet without CLA; a diet with either 1% cis 9, trans 11 CLA or 1% trans 10, cis 12 CLA;
or a mixture of both isomers (1% of each) for 6 weeks. We observed that the exercise decreased
lipogenic enzyme activities in epididymal and perirenal adipose tissue. Plasma cholesterol, insulin,
and leptin concentrations were lower in exercise-trained rats than in sedentary rats. The ingestion
of either CLA mixture or the trans 10, cis 12 CLA increased lipogenic enzyme activities in
epididymal tissue and more markedly in perirenal adipose tissue, especially in sedentary rats, and
without affecting adipose tissue weight or cellularity. A similar effect of trans 10, cis 12 CLA was
observed in regard to malic enzyme activity in the liver. In addition, this isomer decreased plasma
lipid and urea concentrations and increased plasma 3-hydroxybutyrate levels. The ingestion of cis
9, trans 11 CLA increased fatty acid synthase activity in perirenal adipose tissue in sedentary rats
and decreased plasma cholesterol and leptin concentrations. These results show that isomers of
CLA decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose
weight in adult sedentary or exercise-trained rat, thus suggesting a stimulation of adipose tissue
turnover.
PMID: 15607647 [PubMed - indexed for MEDLINE]
J Nutr Biochem. 2004 Nov;15(11):680-7.
Related Articles, Links
Prolonged feeding of mice with conjugated linoleic acid increases
hepatic fatty acid synthesis relative to oxidation.
Javadi M, Beynen AC, Hovenier R, Lankhorst A, Lemmens AG, Terpstra AH, Geelen MJ.
Department of Nutrition, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, P.O.
Box 80.152, 3508 TD Utrecht, The Netherlands.
Feeding mice conjugated linoleic acid (9 cis,11 trans/9 trans,11 cis-and 10 trans,12 cis-CLA in
equal amounts) resulted in triacylglycerol accumulation in the liver. The objective of this study
was to examine whether this steatosis is associated with changes in hepatic fatty acid synthesis and
oxidation. Therefore, we measured the activities of key enzymes of fatty acid synthesis, i.e.,
acetyl-CoA carboxylase and fatty acid synthase and of fatty acid oxidation, i.e., 3-hydroxy-acylCoA dehydrogenase and citrate synthase in livers of mice fed a diet with 0.5% (w/w) CLA. CLA
(a 1:1 mixture of the 10 trans, 12 cis and 9 cis, 11 trans isomers of octadecadenoic acid) was
administered for 3 and 12 weeks with high-oleic sunflower oil fed as control. The proportion of
body fat was significantly lower on the CLA than on the control diet and this effect was already
significant after 3 weeks. The specific activites of 3-hydroxy-acyl-CoA dehydrogenase and citrate
synthase were unaffected by CLA both after 3 and 12 weeks. The specific activity of fatty acid
synthase was nonsignificantly raised (by 12%) after 3 weeks on the CLA diet but had increased
significantly (by 34%) after 12 weeks of feeding. The specific activity of acetyl-CoA carboxylase
had also increased both after 3 weeks (by 53%) and 12 weeks (by 23%) on the CLA diet, but this
effect did not reach statistical significance. Due to CLA-induced hepatomegaly, the overall
capacity for both fatty acid oxidation and synthesis-as evidenced by the total hepatic activities of
3-hydroxy-acyl-CoA dehydrogenase, citrate synthase, acetyl-CoA carboxylase, and fatty acid
synthase-was significantly greater in the CLA-fed group after 12 weeks, although the overall
capacity for fatty acid synthesis had increased more than that for fatty acid oxidation. Thus, this
study indicates that prolonged, but not short-term, feeding mice with CLA increased hepatic fatty
acid synthesis relative to oxidation, despite the decrease in body fat and the increase in liver
weight seen earlier. It is concluded that the observed CLA-induced changes in hepatic fatty acid
synthesis and oxidation are the result, rather than the cause, of the lowering of body fat.
PMID: 15590272 [PubMed - indexed for MEDLINE]
Am J Clin Nutr. 2004 Jun;79(6):1118-25.
Related Articles, Links
Conjugated linoleic acid supplementation for 1 y reduces body fat
mass in healthy overweight humans.
Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O.
Scandinavian Clinical Research AS, Kjeller, Norway. [email protected]
BACKGROUND: Short-term trials showed that conjugated linoleic acid (CLA) may reduce body
fat mass (BFM) and increase lean body mass (LBM), but the long-term effect of CLA was not
examined. OBJECTIVE: The objective of the study was to ascertain the 1-y effect of CLA on
body composition and safety in healthy overweight adults consuming an ad libitum diet. DESIGN:
Male and female volunteers (n = 180) with body mass indexes (in kg/m(2)) of 25-30 were
included in a double-blind, placebo-controlled study. Subjects were randomly assigned to 3
groups: CLA-free fatty acid (FFA), CLA-triacylglycerol, or placebo (olive oil). Change in BFM,
as measured by dual-energy X-ray absorptiometry, was the primary outcome. Secondary outcomes
included the effects of CLA on LBM, adverse events, and safety variables. RESULTS: Mean (+/SD) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 +/- 9.1% and 6.9 +/- 9.1%,
respectively, lower than that in the placebo group (P < 0.001). Subjects receiving CLA-FFA had
1.8 +/- 4.3% greater LBM than did subjects receiving placebo (P = 0.002). These changes were
not associated with diet or exercise. LDL increased in the CLA-FFA group (P = 0.008), HDL
decreased in the CLA-triacylglycerol group (P = 0.003), and lipoprotein(a) increased in both CLA
groups (P < 0.001) compared with month 0. Fasting blood glucose concentrations remained
unchanged in all 3 groups. Glycated hemoglobin rose in all groups from month 0 concentrations,
but there was no significant difference between groups. Adverse events did not differ significantly
between groups. CONCLUSION: Long-term supplementation with CLA-FFA or CLAtriacylglycerol reduces BFM in healthy overweight adults.
Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 15159244 [PubMed - indexed for MEDLINE]
Med Sci Sports Exerc. 2004 May;36(5):814-20.
Related Articles, Links
Conjugated linoleic acid improves insulin sensitivity in young,
sedentary humans.
Eyjolfson V, Spriet LL, Dyck DJ.
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario,
Canada.
BACKGROUND: Preliminary evidence in obese diabetic rats suggests that conjugated linoleic
acid (CLA) may have antidiabetic properties, based on reductions in fasting glucose and insulin
concentrations. However, in lean rats, CLA causes hyperinsulinemia. Furthermore, experiments in
humans also suggest that CLA may worsen insulin sensitivity. OBJECTIVES: The present study
examined whether CLA supplementation can improve insulin sensitivity in humans. DESIGN::
Sixteen young sedentary individuals (age, 21.5 +/- 0.4 yr (mean +/- SEM); body mass, 77.6 +/- 3.4
kg) participated in this study. Ten subjects received 4 g x d of mixed CLA isomers (35.5%cis-9,
trans-11; 36.8%trans-10, cis-12) for 8 wk, whereas six subjects received placebo (safflower oil).
Oral glucose tolerance tests were performed at baseline (0), 4 and 8 wk of supplementation.
RESULTS:: After 8 wk of CLA supplementation, insulin sensitivity index (ISI) increased (14.4
+/- 1.0, 8 wk vs 11.3 +/- 1.3, 0 wk; P < 0.05), which corresponded to a decrease in fasting insulin
concentrations. Six of the 10 subjects showed large increases in their ISI (range, +27 to 90%),
whereas two demonstrated essential no change (+3 to 5%), and two had a decrease in insulin
sensitivity (-12 to -13%). ISI was unchanged over 8 wk in the placebo group. CONCLUSIONS:
Our results indicate that a common dosage of a commercially available CLA supplement can
improve ISI in young, sedentary individuals. However, there is considerable individual variability
in the response. Additional studies are required to identify underlying metabolic changes in human
skeletal muscle.
Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 15126715 [PubMed - indexed for MEDLINE]
Biochim Biophys Acta. 2001 Oct 31;1533(3):233-42.
Related Articles, Links
Influence of conjugated linoleic acid on body composition and target
gene expression in peroxisome proliferator-activated receptor alphanull mice.
Peters JM, Park Y, Gonzalez FJ, Pariza MW.
Department of Veterinary Science and Center for Molecular Toxicology, Pennsylvania State
University, University Park, PA 16802, USA. [email protected]
The mechanisms underlying the beneficial effects of conjugated linoleic acid (CLA) are unknown,
but one hypothesis is that they are mediated by the nuclear receptor, peroxisome proliferatoractivated receptor (PPARalpha). In this work, the effect of dietary CLA on body weight gain,
body composition, serum lipids and tissue specific PPAR target gene expression was examined in
PPARalpha-null mice. Male wild-type or PPARalpha-null mice were fed either a control diet or
one containing 0.5% CLA for a period of 4 weeks. Weight gain in wild-type and PPARalpha-null
mice fed CLA was similar, and significantly less than controls. Whole body fat content was lower
in wild-type and PPARalpha-null mice while whole body protein content was increased in both
genotypes fed CLA compared to controls. Serum triglycerides were lowered in both genotypes as
a result of dietary CLA. While CLA feeding resulted in specific activation of PPARalpha in liver,
alterations in liver, adipose and muscle mRNAs were also found that were independent of
PPARalpha genotype including those encoding uncoupling proteins (UCPs), mitochondrial fatty
acid oxidizing enzymes, and fatty acid transporter. These results demonstrate that despite specific
activation of PPARalpha-dependent gene expression, the influence of CLA on body composition
appears to be independent of PPARalpha. Further, CLA causes increased levels of mRNAs
encoding lipid metabolizing and mitochondrial uncoupling proteins that likely contribute to the
mechanisms underlying reduced fat/increased lean body mass resulting from consumption of
dietary CLA.
PMID: 11731333 [PubMed - indexed for MEDLINE]
J Biol Chem. 2004 Jun 18;279(25):26735-47. Epub 2004 Apr 2.
Related Articles, Links
Conjugated linoleic acid induces human adipocyte delipidation:
autocrine/paracrine regulation of MEK/ERK signaling by
adipocytokines.
Brown JM, Boysen MS, Chung S, Fabiyi O, Morrison RF, Mandrup S, McIntosh MK.
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina
27402-6170, USA.
Dietary conjugated linoleic acid (CLA) reduces body fat in animals and some humans. Here we
show that trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, when added to cultures of stromal
vascular cells containing newly differentiated human adipocytes, caused a time-dependent
decrease in triglyceride content, insulin-stimulated glucose and fatty acid uptake, incorporation
into lipid, and oxidation compared with controls. In parallel, gene expression of peroxisome
proliferator-activated receptor-gamma and many of its downstream targets were diminished by
trans-10, cis-12 CLA, whereas leptin gene expression was increased. Prior to changes in gene
expression and metabolism, trans-10, cis-12 CLA caused a robust and sustained activation of
mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK) signaling.
Furthermore, the trans-10, cis-12 CLA-mediated activation of MEK/ERK could be attenuated by
pretreatment with U0126 and pertussis toxin. In parallel, pretreatment with U0126 blocked the
ability of trans-10, cis-12 CLA to alter gene expression and attenuate glucose and fatty acid uptake
of the cultures. Intriguingly, the induction by CLA of MEK/ERK signaling was linked to
hypersecretion of adipocytokines interleukin-6 and interleukin-8. Collectively, these data
demonstrate for the first time that trans-10, cis-12 CLA decreases the triglyceride content of newly
differentiated human adipocytes by inducing MEK/ERK signaling through the autocrine/paracrine
actions of interleukins-6 and 8.
PMID: 15067015 [PubMed - indexed for MEDLINE]
J Nutr. 2003 Oct;133(10):3041-6.
Related Articles, Links
Conjugated linoleic acid in humans: regulation of adiposity and
insulin sensitivity.
Brown JM, McIntosh MK.
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 274026170, USA.
Conjugated linoleic acid (CLA) isomers, a group of positional and geometric isomers of linoleic
acid [18:2(n-6)], have been studied extensively due to their ability to modulate cancer,
atherosclerosis, obesity, immune function and diabetes in a variety of experimental models. The
purpose of this review was to examine CLA's isomer-specific regulation of adiposity and insulin
sensitivity in humans and in cultures of human adipocytes. It has been clearly demonstrated that
specific CLA isomers or a crude mixture of CLA isomers prevent the development of obesity in
certain rodent and pig models. This has been attributed mainly to trans-10, cis-12 CLA, both in
vivo and in vitro. However, CLA's ability to modulate human obesity remains controversial
because data from clinical trials using mixed isomers are conflicting. In support of some studies in
humans, our group demonstrated that trans-10, cis-12 CLA prevents triglyceride (TG)
accumulation in primary cultures of differentiating human preadipocytes. In contrast, cis-9, trans11 CLA increases TG content. Closer examination has revealed that CLA's antiadipogenic actions
are due, at least in part, to regulation of glucose and fatty acid uptake and metabolism. This review
presents our current understanding of potential isomer-specific mechanisms by which CLA
reduces human adiposity and insulin sensitivity.
Publication Types:

Review

Review, Tutorial
PMID: 14519781 [PubMed - indexed for MEDLINE]
J Lipid Res. 2003 Dec;44(12):2234-41. Epub 2003 Aug 16.
Related Articles, Links
Efficacy and safety of dietary supplements containing CLA for the
treatment of obesity: evidence from animal and human studies.
Larsen TM, Toubro S, Astrup A.
Department of Human Nutrition, Center for Advanced Food Studies, The Royal Veterinary and
Agricultural University, DK-1958 Frederiksberg C, Denmark. [email protected]
Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight
loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy
and safety of CLA supplementation based on peer-reviewed published results from randomized,
placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings
from experimental studies in animals and studies performed in vitro. CLA appears to produce loss
of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized,
controlled, short-term (<6 months) trials in humans find little evidence to support that CLA
reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However,
there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12
may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that
resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In
conclusion, although CLA appears to attenuate increases in body weight and body fat in several
animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in
humans and may actually have adverse effects on human health.
Publication Types:

Review

Review, Tutorial
PMID: 12923219 [PubMed - indexed for MEDLINE]