CLA & fat cell apoptosis revisited

virtualcyber

New Member
The following article is about mice cell apoptosis, with CLA administration.

The article is interesting because (1) the experiments were _IN VIVO_ and (2) CLA was administered as part of mice's diet.

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"Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice."

Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O.

Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-alpha and uncoupling protein (UCP)-2 mRNA levels increased 12- and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-alpha induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-alpha mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.
 
great post.
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[b said:
Quote[/b] (virtualcyber @ Sep. 26 2002,5:04)]These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.
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...or Bromocriptine administration
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So what's the take home message of CLA.
VC, you seem quite interested in its potential benefits. Would you mind giving me your take on its efficacy, dosage range, etc.
Appreciate any input...
 
tkarrde

Take home message for tonalin (CLA brand):

(1) It helps you stay leaner (other research results support
this, at about 6 g per day).
(2) It may or may not help you in speeding up fat loss, so
don't look for ECA-like effect.
(3) It has a subtle, long-term effect (3-6 months).
Don't expect short-term effect.

I will try CLA again, but this time, I will try to take it for about 6 months to a year. I need to find a cheap source of tonalin.

It is good to know that it may have the effect of liposuction (killing fat cells) ... But unlike lipo, it has anti-carcinogen properties.

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P.S. Jon Stark seems to have had an interesting result, which he posted at muscleandmind.com forum. His take is that it maybe helping him stay lean. He said that he used CLA for about 3 months. He said he was unimpressed with its effect regarding fat loss. Then, he talked about pigging out for a week on a cruise but still not gaining weight. I would dismiss his story as one of zillion bb supplement anecdotes, except that ... from looking at his past posts at various forums, I get the impression he is careful and knows what he is talking about.

I took CLA for about 2-3 weeks. Because I have not noticed accelerated fat loss, I stopped taking it. Obviously,
I did not take CLA long enough. Also, I was looking for the &quot;wrong&quot; benefit from CLA, that is, the accelerated fat loss. Even if there is one, it is probably not easily noticeable -- this is consistent with what Jon Stark wrote.
 
Hey, yeah, I posted a little anecdote about my CLA experience over on that other board under a thread about &quot;reseting your set-point&quot; or something. I won't bore you with it here, virtualcyber basically presented the gist of it.

I've been using it continuously for over 3 months now, at like 8 or 9 grams a day. I use Tonalin from Kilosports and the NOW brand CLA from 1fast400. Those are the cheapest sources I've found.

A point I made in that posting that I should re-iterate here on the HST board is that it sure makes deconditioning easier for me to accept. I'm sure there are other guys like me who dread it, and even cut it short because we can't bear not lifting for 9 to 12 days. But after eating like a hog and getting barely any exercise for a week and not putting on any weight, I think future deconditioning periods will be far easier for me psychologically.

I'm hoping that with continued use I'll start seeing more pronounced leaning out. I'll certainly let you all know how it goes.
 
<span style='font-size:9pt;line-height:100%'>Bumping this thread...
I actually have huge questions about CLA, especially after Virtualcyber's post.</span>

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[b said:
Quote[/b] ]However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.
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<span style='font-size:9pt;line-height:100%'>This doesn't sound good. I'm still struggling to understand the action of insulin. Can someone give me a &quot;CLA for Dummies&quot; explanation of this? I think I understand that there is a trade-off here, but I don't know how much weight to put on the downside.</span>
 
Jon Stark:

What they are saying is that there seems to be insulin resistance. In the full article they cite two reasons for this: (1) there is no place for the glucose to go (because fat cells have ... died) and (2) there is market decrease of GLUT4 in adipose tissues.

Lyle had a bit to say about this at misc.fitness.weights:

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[b said:
Quote[/b] ]
Leptin is sort of a schizoid hormone. HIgh concentrations induce insulin resistance (it's one of the ways that the fat cell tries to prevent further fat storage), low concentrations don't let insulin work as well (especially in muscle), medium concentrations give optimal results. But researchers tend to draw somewhat silly conclusions because of that fact.
(muscle.fitness.weights)
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There is another noteworthy fact from the experiment, and that is enlargement of liver. CLA fed mice had liver which were 4 x larger than those mice that were not fed CLA.

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Quote[/b] ]
However, the liver was massively enlarged and very pale, suggesting deposition of fat (Fig. 1Band C). CLA-fed mice showed 3.6-fold (P &lt; 0.001) and 1.6-fold (NS) enlargement of liver and spleen, respectively.

Histological analysis of liver revealed that there was panlobular macrovesicular steatosis but no increased hepatic inflammation (Fig. 6C). Liver enlargement was manifested 14 days after CLA supplementation (data not shown). No enlargement of the kidney, heart, or skeletal muscles was noted. Despite these marked phenotypic changes,
the average energy intake in the 2 groups was not significantly different (7.4 ± 0.5 and 7.7 ± 0.9 kcal · mouse &amp;#8211;1 · day &amp;#8211;1 in control and CLA-fed mice, respectively; n = 5).
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Additional facts about the experiment.

CLA administration duration: 8 months
CLA by calories: 2-3 % (not much ...)

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Body weight and tissue weight in each group of mice
without CLA / with CLA

Initial body weight: (g) 17.5 ± 0.2 (14) / 17.6 ± 0.2 (14)
Final body weight: (g) 29.3 ± 1.1 (13) / 27.6 ± 0.9 (13)
WAT
Parametrial wt: (g) 1.33 ± 0.14 (14) / 0.36 ± 0.05 (14)
Renal weight (g) 0.42 ± 0.10 (5) / 0.03 ± 0.01 (5)
Retroperitoneal 0.29 ± 0.06 (5) / ND (5)
weight (g)

Abdominal 1.11 ± 0.21 (5) / 0.04 ± 0.01 (5)*
subcutaneous weight (g)

Dorsal subcutaneous 0.76 ± 0.16 (5) / 0.02 ± 0.00 (5)
weight (g)

BAT weight (g) 0.14 ± 0.01 (14) / ND(14)
Liver weight (g) 1.24 ± 0.07 (14) / 4.44 ± 0.43 (14)*
Spleen weight (g) 0.10 ± 0.01 (5) / 0.16 ± 0.02 (5)
Kidney weight (g) 0.27 ± 0.01 (5) / 0.28 ± 0.01 (5)
Heart weight (g) 0.13 ± 0.00 (5) / 0.15 ± 0.01 (5)

Skeletal muscles
Gastrocnemius 0.23 ± 0.01 (5) / 0.24 ± 0.01 (5)
weight (g)

Quadriceps weight (g) 0.24 ± 0.02 / (5) 0.25 ± 0.02 (5)
 
Holy geeze.

I wonder how to proceed? Cycle CLA? Stack it with insulin sensitizers (and maybe quit all other insulin desensitizers)?

Even if you were able to address the insulin issue, the liver thing is worrisome. Of course, the research is on rats.

I also wonder how a pure trans-10 cis-12 CLA product would behave with regard to insulin and liver hypertrophy... (It would be nice is all the downsides were attributable to an isomer that could be removed.)
 
What to conclude? I think the safe thing is to stop the administration. Your liver is probably one of the most important organs in your body; you don't want to play roulette with it, until we have more information that indicates (1) there is no enlargement in human beings and (2) if so, such liver &quot;enlargement&quot; is beneficial or good for human body.

Insulin issue does not worry me as much, because even if that particular issue was relevant to human beings, excess sugar can go to muscle cells (GLUT4). Also, with regard to adipose tissue, you can replenish them -- just stop taking CLA.

I am worried more about liver enlargement. (1) I don't know if it is applicable to humans (2) I don't know if it is a reversible process (3) and it might be harmful.

From what has been described in the paper, it seems that liver is trying to compensate for the role of dead subcutaneous fat cells. In other words, fat becomes &quot;redistributed&quot; (goes away from underneath your skin) to the liver.
 
Yes, the liver issue is the most worrisome part.

Bryan, what's your take on all this?

(Also, is there some test for liver enlargement? Besides cutting into me?)
 
On the insulin resistance, Bryan summarized some lit on CLA and one of the findings he pointed out was that CLA increased insulin sensitivity.

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[b said:
Quote[/b] ]The reason CLA has been labeled a &quot;partitioning agent&quot; is because of its ability to increase the uptake of energy into muscle tissue and the ability to blunt energy intake into fat cells. As mentioned above, this ability to increase insulin sensitivity in muscle tissue is also attributed to CLA activity as a PPAR agonist. (Houseknecht, K. L., J. P. Vanden Heuvel, S. Y. Moya-Camarena, C. P. Portocarrero, L. W. Peck, K. P. Nickel, and M. A. Belury. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem. Biophys. Res. Commun. 244: 678-682, 1998) So you are starving the fat and feeding your muscle, the end result being an increase or maintenance of muscle mass and a reduction in fat.
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http://musclemonthly.com/article....ork.htm

He's talking about Tonalin CLA. I wonder what the isomer profile was of the CLA used in the rats-with-giant-livers research.
 
Jon Stark:

The isomer profile is as same as that of Tonalin (this was given in the full text of the article).

Here is what Lyle had to say about the potential negative effects of CLA, from misc.fitness.weights (usenet). Someone asked Lyle if &quot; does that (the study) contra-indicate CLA use in humans??&quot;

He replied:

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[b said:
Quote[/b] ]
Thinking about this some more, most of the stuff on CLA in humans tends to show pretty much only good things: improved lipid profiles, it's anti-carcinogenic, etc. Wouldn't really go hand in hand with having negative effects on liver metabolism.

I really think that the enlarged liver in this rat study had to do with the severe loss of fat cells. Without a place to 'go' (i.e. fat cells), glucose and fats tend to accumulate in places like the liver and bloodstream, causing problems.

And rats just seem to metabolize CLA differently, which is why they get these profound effects on bodyfat that relaly haven't shown up in the human studies.

That said, I'm not honestly convinced that CLA is going to have a huge effect (in terms of fat loss) in humans, but I don't see why it's going to be contraindicated.
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Lyle is basically saying he does not see real reason why one should stop using CLA.
 
Hi guys, not to get off the CLA subject, but something else about that study poped out at me. I noticed that there was marked insulin resistace with the decline of Leptin levels, but was reversed when leptin was normalized. After coming off a long cutting cycle and adding carbs back in along with increased calories I have noticed I have put on some fat around my low abs. This happened rather quickly. I did a 14 day deconditioning, and due to circumstances my diet was all over the place. Then, when I started the next cycle with the 15s, I trainied full body daily for two weeks with only 2 days off. With the increased frequency, I thought I would actually drop some fat as I was only eating at or slightly above my previous maintenance level. Since I have increased my carbs to about 1.5 times what they were it seems that I am much more sensitive to them even with the increase in activity.


I am wondering if the increased fat is due to the rebound of coming off my low carb diet (insulin resistance), or if it's my body trying to get back to my &quot;set point&quot; after running on a deficit for so long. Any thoughts or ideas on this?


Oh, and happy Birthday VC. One more year to go before the big 40!!


Steve
 
Steve

Thanks for the birthday notice! Yeah, big 40. lol, I am doing my facebuilding exercises everyday ... :)

[you wrote]
&gt; After coming off a long cutting cycle and adding carbs back
&gt; in along with increased calories I have noticed I have put
&gt; on some fat around my low abs. This happened rather
&gt; quickly. I did a 14 day deconditioning, and due to
&gt; circumstances my diet was all over the place.

Are you sure that it is fat? Ihe first thing I notice when I eat a lot of carbs is an increase in body weight. But it is not fat -- it is just water + glycogen. Furthermore, even though it is just water + glycogen, muscle definition decreases. This can happen really fast.

What is interesting is that, once that initial weight increase has occurred, any excess food intake will eventually go to your bod's favorite fat depot. I suppose 4 weeks (SD + 2 weeks of 15's) is long enough for the fat accumulation to occur, depending on caloric surplus -- but it may not be as bad as you think ...

&gt; Then, when I started the next cycle with the 15s, I trainied
&gt; full body daily for two weeks with only 2 days off. With the
&gt; increased frequency, I thought I would actually drop some
&gt; fat as I was only eating at or slightly above my previous
&gt; maintenance level. Since I have increased my carbs to
&gt; about 1.5 times what they were it seems that I am much
&gt; more sensitive to them even with the increase in activity.

I think that is true. Fat does accumulate faster when you are at low bf% ... As you mentioned, I suppose this all comes down to your bf set point (or leptin set point).
 
Thanks VC. It could be just that. I had about two weeks that I didn't really eat well at all. It could just be a psychological thing. I really didn't eat that much over maintenance during the 15s, and I was probably below maintenance for my SD. I think I just hate my set point.

Steve
 
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