LE Magazine August 2002
Influence of conjugated linoleic acid
(CLA) on establishment and progression of atherosclerosis in
rabbits.
OBJECTIVE: To determine effects of conjugated linoleic acid
(CLA) on the establishment and progression of
experimentally-induced atherosclerosis in rabbits. METHODS:
For establishment of atherosclerosis, New Zealand White
rabbits were fed a semipurified diet containing 0.1% to 0.2%
cholesterol for 90 days. Some groups were fed diet and CLA.
For effects on progression of atherosclerosis, rabbits with
established atherosclerosis were fed a semipurified diet +/-
CLA for 90 days. RESULTS: At dietary levels as low as 0.1%,
CLA inhibited atherogenesis. At dietary levels of 1%, CLA
caused substantial (30%) regression of established
atherosclerosis. This is the first example of substantial
regression of atherosclerosis being caused by diet alone.
CONCLUSION: Dietary CLA is an effective inhibitor of
atherogenesis and also causes regression of established
atherosclerosis.
J Am Coll Nutr 2000
Aug;19(4):472S-477S
Effect of conjugated linoleic acid on
body composition in mice.
The effects of conjugated linoleic acid (CLA) on body
composition were investigated. ICR mice were fed a control
diet containing 5.5% corn oil or a CLA-supplemented diet (5.0%
corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet
exhibited 57% and 60% lower body fat and 5% and 14% increased
lean body mass relative to controls (P < 0.05). Total
carnitine palmitoyltransferase activity was increased by
dietary CLA supplementation in both fat pad and skeletal
muscle; the differences were significant for fat pad of fed
mice and skeletal muscle of fasted mice. In cultured 3T3-L1
adipocytes CLA treatment (1 x 10(-4)M) significantly reduced
heparin-releasable lipoprotein lipase activity (-66%) and the
intracellular concentrations of triacylglyceride (-8%) and
glycerol (-15%), but significantly increased free glycerol in
the culture medium (+22%) compared to control (P < 0.05).
The effects of CLA on body composition appear to be due in
part to reduced fat deposition and increased lipolysis in
adipocytes, possibly coupled with enhanced fatty acid
oxidation in both muscle cells and adipocytes.
Lipids 1997 Aug;32(8):853-8
Conjugated linoleic acid (CLA) reduced
abdominal adipose tissue in obese middle-aged men with signs
of the metabolic syndrome: a randomized controlled trial.
BACKGROUND: Abdominal obesity is strongly related to
metabolic disorders. Recent research suggests that dietary
conjugated linoleic acid (CLA) reduces body fat and may
improve metabolic variables in animals. The metabolic effects
of CLA in abdominally obese humans have not yet been tested.
OBJECTIVE: To investigate the short-term effect of CLA on
abdominal fat and cardiovascular risk factors in middle-aged
men with metabolic disorders. METHODS: Twenty-five abdominally
obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass
index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between
39 and 64-y-old participated in a double-blind randomised
controlled trial for 4 weeks. Fourteen men received 4.2 g
CLA/day and 10 men received a placebo. The main endpoints were
differences between the two groups in sagittal abdominal
diameter (SAD), serum cholesterol, low-density lipoprotein,
high-density lipoprotein, triglycerides, free fatty acids,
glucose and insulin. RESULTS: At baseline, there were no
significant differences between groups in anthropometric or
metabolic variables. After four weeks there was a significant
decrease in SAD (cm) in the CLA group compared to placebo
(P=0.04, 95% CI; -1.12, -0.02). Other measurements of
anthropometry or metabolism showed no significant differences
between the groups. CONCLUSIONS: These results indicate that
CLA supplementation for four weeks in obese men with the
metabolic syndrome may decrease abdominal fat, without
concomitant effects on overall obesity or other cardiovascular
risk factors. Because of the limited sample size, the effects
of CLA in abdominal obesity need to be further investigated in
larger trials with longer duration.
Int J Obes Relat Metab Disord 2001
Aug;25(8):1129-35
Effects of conjugated linoleic acid on
body fat and energy metabolism in the mouse.
Conjugated linoleic acid (CLA) is a naturally occurring
group of dienoic derivatives of linoleic acid found in the fat
of beef and other ruminants. CLA is reported to have effects
on both tumor development and body fat in animal models. To
further characterize the metabolic effects of CLA, male AKR/J
mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet
with or without CLA (2.46 mg/kcal; 1.2% and 1.0% by weight in
high- and low-fat diets, respectively) for six weeks. CLA
significantly reduced energy intake, growth rate, adipose
depot weight, and carcass lipid and protein content
independent of diet composition. Overall, the reduction of
adipose depot weight ranged from 43% to 88%, with the
retroperitoneal depot most sensitive to CLA. CLA significantly
increased metabolic rate and decreased the nighttime
respiratory quotient. These findings demonstrate that CLA
reduces body fat by several mechanisms, including a reduced
energy intake, increased metabolic rate, and a shift in the
nocturnal fuel mix.
Am J Physiol 1998 Sep;275(3 Pt
2):R667-72
Dietary conjugated linoleic acids
increase lean tissue and decrease fat deposition in growing
pigs.
Conjugated linoleic acid (CLA) decreases the body fat
content of rodents. The aim of this study was to determine
whether dietary CLA altered carcass composition of pigs.
Female Large White x Landrace pigs (n = 66) were used in this
study. To obtain initial body composition, six pigs were
slaughtered at 57 kg live weight, whereas the remaining pigs
were allocated to one of six dietary treatments (0, 1.25, 2.5,
5.0, 7.5 and 10.0 g/kg CLA, containing 55% of CLA isomers).
The diets, containing 14.3 MJ digestible energy (DE) and 9. 3
g available lysine per kg, were fed ad libitum for eight
weeks. Dietary CLA had no significant effect on average daily
gain (861 vs. 911 g/d for pigs fed diets with and without CLA,
P = 0.15) or feed intake (2. 83 vs. 2.80 kg/d, P = 0.74). The
gain to feed ratio was increased by dietary CLA by 6.3% (0.328
vs. 0.348, P = 0.009). Fat deposition decreased linearly (-8.2
+/- 2.09 g/d for each gram per kilogram increase in CLA
concentration; P < 0.001) with increasing inclusion of CLA.
At the highest level of CLA inclusion, fat deposition was
decreased by 88 g/d (-31%). Similarly, the ratio of fat to
lean tissue deposition decreased linearly (-0.093 +/- 0.0216
for each gram per kilogram increase in CLA concentration; P
< 0.001) with increasing dietary CLA. The carcass lean
tissue deposition response to dietary CLA was quadratic in
nature and was maximized (+25%) at 5. 0 g/kg dietary CLA.
Overall, dietary CLA increased the gain to feed ratio and lean
tissue deposition and decreased fat deposition in finisher
pigs.
J Nutr 1999 Nov;129(11):2037-42
Conjugated linoleic acid reduces body
fat mass in overweight and obese humans.
Conjugated linoleic acid (CLA) has been shown to reduce
body fat mass (BFM) in animals. To investigate the
dose-response relationships of conjugated linoleic acid with
regard to BFM in humans, a randomized, double-blind study
including 60 overweight or obese volunteers (body mass index
25 to 35 kg/m(2)) was performed. The subjects were divided
into five groups receiving placebo (9 g olive oil), 1.7, 3.4,
5.1 or 6.8 g conjugated linoleic acid per day for 12 weeks,
respectively. Dual-energy X-ray absorptiometry was used to
measure body composition [measurements at week 0 (baseline),
six and 12]. Of the 60 subjects, 47 completed the study. Eight
subjects withdrew from the study due to adverse events;
however, no differences among treatment groups were found
regarding adverse events. Repeated-measures analysis showed
that a significantly higher reduction in BFM was found in the
conjugated linoleic acid groups compared with the placebo
group (P: = 0.03). The reduction of body fat within the groups
was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05
and P: = 0.02, respectively). No significant differences among
the groups were observed in lean body mass, body mass index,
blood safety variables or blood lipids. The data suggest that
conjugated linoleic acid may reduce BFM in humans and that no
additional effect on BFM is achieved with doses > 3.4 g
CLA/d.
J Nutr 2000 Dec;130(12):2943-8
Conjugated linoleic acid-enriched
butter fat alters mammary gland morphogenesis and reduces
cancer risk in rats.
Conjugated linoleic acid (CLA) is a potent cancer
preventive agent in animal models. To date, all of the in vivo
work with CLA has been done with a commercial free fatty acid
preparation containing a mixture of c9, t11-, t10, c12- and
c11, t13-isomers, although CLA in food is predominantly (80%
to 90%) the c9, t11-isomer present in triacylglycerols. The
objective of this study was to determine whether a high CLA
butter fat has biological activities similar to those of the
mixture of free fatty acid CLA isomers. The following four
different endpoints were evaluated in rat mammary gland: 1)
digitized image analysis of epithelial mass in mammary whole
mount; 2) terminal end bud (TEB) density; 3) proliferative
activity of TEB cells as determined by proliferating cell
nuclear antigen immunohistochemistry; and 4) mammary cancer
prevention bioassay in the methylnitrosourea model. It should
be noted that TEB cells are the target cells for mammary
chemical carcinogenesis. Feeding butter fat CLA to rats during
the time of pubescent mammary gland development reduced
mammary epithelial mass by 22%, decreased the size of the TEB
population by 30%, suppressed the proliferation of TEB cells
by 30% and inhibited mammary tumor yield by 53% (P < 0.05).
Furthermore, all of the above variables responded with the
same magnitude of change to both butter fat CLA and the
mixture of CLA isomers at the level of CLA (0.8%) present in
the diet. Interestingly, there appeared to be some selectivity
in the uptake or incorporation of c9, t11-CLA over t10,
c12-CLA in the tissues of rats given the mixture of CLA
isomers. Rats consuming the CLA-enriched butter fat also
consistently accumulated more total CLA in the mammary gland
and other tissues (four- to six-fold increases) compared with
those consuming free fatty acid CLA (three-fold increases) at
the same dietary level of intake. We hypothesize that the
availability of vaccenic acid (t11-18:1) in butter fat may
serve as the precursor for the endogenous synthesis of CLA via
the Delta9-desaturase reaction. Further studies will be
conducted to investigate other attributes of this novel dairy
product.
J Nutr 1999 Dec;129(12):2135-42
Carnitine/DHEA
Dehydroepiandrosterone alters Zucker
rat soleus and cardiac muscle lipid profiles.
High levels of serum free fatty acids (FFA) and lower
proportions of polyunsaturated (PU) FAs, specifically
arachidonic acid (AA), are common in obesity, insulin
resistance (IR), and type 2 diabetes mellitus.
Dehydroepiandrosterone (DHEA) decreases body fat content,
dietary fat consumption and insulin levels in obese Zucker
rats (ZR), a genetic model of human youth onset obesity and
type 2 diabetes. This study was conducted to investigate
DHEA’s effects on lean and obese ZR serum FFA levels and
total lipid (TL) FA profiles in heart and soleus muscle. We
postulated that DHEA alters serum FFA levels and tissue TL FA
profiles of obese ZR so that they resemble the levels and
profiles of lean ZR. If so, DHEA may directly or indirectly
alter tissue lipids, FFA flux, and perhaps lower IR in obese
ZR. Lean and obese male ZR were divided into six groups with
10 animals in each: obese ad libitum control, obese pair-fed,
obese DHEA, lean ad libitum control, lean pair-fed, and lean
DHEA. All animals had ad libitum access to a diet whose
calories were 50% fat, 30% carbohydrate and 20% protein. Only
the diets of the DHEA treatment groups were supplemented with
0.6% DHEA. Pair-fed groups were given the average number of
calories per day consumed by their corresponding DHEA group,
and ad libitum groups had 24-h access to the DHEA-free diet.
Serum FFA levels and heart and soleus TL FA profiles were
measured. Serum FFA levels were higher in obese (approximately
1 mmol/L) compared to lean (approximately 0.6 mmol/L) ZR,
regardless of group. In hearts, monounsaturated (MU) FA were
greater and PU FA were proportionally lower in obese compared
to the lean rats. In soleus, saturated and MU FA were greater
and PU FA were proportionally lower in the obese compared to
the lean rats. DHEA groups displayed significantly increased
proportions of TL AA and decreased oleic acid in both muscle
types. Mechanisms by which DHEA alters TL FA profiles are a
reflection of changes occurring within specific lipid
fractions such as FFA, phospholipid, and triglyceride. This
study provides initial insights into DHEA’s lipid
altering effects.
Exp Biol Med (Maywood) 2001
Sep;226(8):782-9
Dehydroepiandrosterone alters
phospholipid profiles in Zucker rat muscle tissue.
Insulin-resistant muscle tissue contains low proportions of
arachidonic acid (AA), and increased proportions of muscle AA
correlate with improved insulin sensitivity.
Dehydroepiandrosterone (DHEA) and AA, like the
thiazolidinedione drugs that decrease insulin resistance (IR),
are peroxisome proliferators. Long-chain fatty acids (FA) have
been named the “one true” endogenous ligand for
activating the peroxisome proliferator-activator receptor
(PPAR), and DHEA has been named a “good candidate”
as a naturally occurring indirect activator of PPAR. This
study was conducted to determine DHEA’s effects on lipid
profiles of skeletal and cardiac muscle in lean and obese
Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and
obesity. We hypothesize that DHEA may alter long-chain FA
profiles in muscle tissue of obese rats such that they more
closely resemble that of the lean. In our experiments, we
employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean
and 12 obese ZR. For 30 d, the diet of the two DHEA groups was
supplemented with 0.6% DHEA; PF groups were given the average
daily calories consumed by their corresponding treatment
group. Hearts and gastrocnemius muscles were assayed for
phospholipid (PL), free FA, and triglyceride (TG) FA profiles.
The proportion of PL AA was significantly greater in both
muscle types of lean compared to obese rats. Hearts from both
DHEA groups had greater PL proportions of AA and less oleic
(18:1) acid than their PF controls. Likewise, 18:1 proportions
were significantly lower in the gastrocnemius; however, AA
proportions were not significantly different. Similar
phenotypic profile differences were observed in the TG
fraction of both muscle types. There were no DHEA-related TG
FA profile alterations.
Lipids 2001 Dec;36(12):1383-6
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