Hmm... Forskolin Suppresses Expresion of ATGL...

[Grayson]

Thyroid-Stimulating Hormone Inhibits Adipose Triglyceride Lipase in 3T3-L1 Adipocytes through the PKA Pathway

PLOS ONE: Thyroid-Stimulating Hormone Inhibits Adipose Triglyceride Lipase in 3T3-L1 Adipocytes through the PKA Pathway

Abstract

Thyroid-stimulating hormone (TSH) has been shown to play an important role in the regulation of triglyceride (TG) metabolism in adipose tissue. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis of TG. Thus far, it is unclear whether TSH has a direct effect on the expression of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this study to determine the effects of TSHR deletion on ATGL expression. These effects were verified in 3T3-L1 adipocytes and potential underlying mechanisms were explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was significantly increased compared with that in Tshr+/+ mice. ATGL expression was observed to increase with the differentiation process of 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1 adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH has an inhibitory effect on ATGL expression in mature adipocytes. The associated mechanism is related to PKA activation.

 

[Jakethaniel]

Thanks for the informative post! This is really interesting information to take into account for a fat burning proprietary blend I am working on.

 

[Danes]

It's just something to keep in mind.

Interessing

 

[jp_x_type]

More and more research to reinforce Forskolin's already high reputation (unless I misunderstood the technicalities of the study

Does anyone have an explanation why the 25mg forskolin I take in the morning seems to make me a bit sleepy at first, whereas the same dose I take in the afternoon gives me an energy boost similar to 50mg caffeine?

Also, what exactly are the GI issues people frequently report from taking coleus?

I use the Forslean patented brand (Planetary Herbals and Vitacost) coupled with a cap of Tropinol XP (so I get roughly 75mg forskolin daily) and I've never noticed a negative impact on my very sensitive GI tract.

Can someone explain how coleus could negatively impact the GI tract and what exactly does it result in? Diarrhea? Nausea?

 

[Danes]

More and more research to reinforce Forskolin's already high reputation (unless I misunderstood the technicalities of the study

Does anyone have an explanation why the 25mg forskolin I take in the morning seems to make me a bit sleepy at first, whereas the same dose I take in the afternoon gives me an energy boost similar to 50mg caffeine?

Also, what exactly are the GI issues people frequently report from taking coleus?

I use the Forslean patented brand (Planetary Herbals and Vitacost) coupled with a cap of Tropinol XP (so I get roughly 75mg forskolin daily) and I've never noticed a negative impact on my very sensitive GI tract.

Can someone explain how coleus could negatively impact the GI tract and what exactly does it result in? Diarrhea? Nausea?

I felt upset stomach. Apetitte was destroyed

 

[kbayne]

More and more research to reinforce Forskolin's already high reputation (unless I misunderstood the technicalities of the study Does anyone have an explanation why the 25mg forskolin I take in the morning seems to make me a bit sleepy at first, whereas the same dose I take in the afternoon gives me an energy boost similar to 50mg caffeine? Also, what exactly are the GI issues people frequently report from taking coleus? I use the Forslean patented brand (Planetary Herbals and Vitacost) coupled with a cap of Tropinol XP (so I get roughly 75mg forskolin daily) and I've never noticed a negative impact on my very sensitive GI tract. Can someone explain how coleus could negatively impact the GI tract and what exactly does it result in? Diarrhea? Nausea?

In most cases, the squirts.

 

[kdubson14]

Doesn't prior research show that cAMP has no effect on ATGL in the murine model?

 

[Jiigzz]

Thyroid-Stimulating Hormone Inhibits Adipose Triglyceride Lipase in 3T3-L1 Adipocytes through the PKA Pathway

PLOS ONE: Thyroid-Stimulating Hormone Inhibits Adipose Triglyceride Lipase in 3T3-L1 Adipocytes through the PKA Pathway

Abstract

Thyroid-stimulating hormone (TSH) has been shown to play an important role in the regulation of triglyceride (TG) metabolism in adipose tissue. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis of TG. Thus far, it is unclear whether TSH has a direct effect on the expression of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this study to determine the effects of TSHR deletion on ATGL expression. These effects were verified in 3T3-L1 adipocytes and potential underlying mechanisms were explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was significantly increased compared with that in Tshr+/+ mice. ATGL expression was observed to increase with the differentiation process of 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1 adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH has an inhibitory effect on ATGL expression in mature adipocytes. The associated mechanism is related to PKA activation.

Where does it mention a forskolin dose?

 

[nattydisaster]

Where does it mention a forskolin dose?

There's no dose because it is not an animal study...its just a petri dish study. So I would not worry especially since there are human studies on forskolin for fat loss. While looking at more petri dish studies, I think this one is more important that the one above:

http://www.ncbi.nlm.nih.gov/pubmed/6327383

Forskolin stimulation of thyroid secretion of T4 and T3.

Forskolin is a potent activator of adenylate cyclase in many tissues including the thyroid gland. We compared the effects of 10(-5) M forskolin and 100 mu units/ml TSH on the dynamics of T4 and T3 secretion from perfused dog thyroid lobes. Both agents induced pronounced increases in T4 and T3 secretion. The increase in secretion was significantly steeper during forskolin than during TSH stimulation. This may suggest that early processes such as TSH-receptor interaction and the subsequent activation of the catalytic unit of adenylate cyclase are of importance for the pattern of very gradual increase in hormone secretion during TSH stimulation of the thyroid. In other respects forskolin seems to induce absolute and relative secretion of T3 and T4 very similar to those obtained by cAMP and TSH.

Use Forskolin-95 to avoid the stomach issues commonly caused by low % extracts

 

[nattydisaster]

What do you disagree with exactly?

 

[Danes]

Use Forskolin-95 to avoid the stomach issues commonly caused by low % extracts

Tried and no difference

 

[JudoJosh]

We can agree to disagree

You do understand the study you posted is one exploring potential mechanisms of how TSH effects triglyceride metabolisim and has no real practical use, especially in regards to forskolin, right?

They are looking at how TSH effect ATGL and the hypothesis is via cAMP & PKA pathway. There is no real practical use about forskolin from here. Forskolin use was to manipulate the cellular environment in order to test if those pathways are indeed responsible for TSHs effect on ATGL.

The study is useful for tying to explore the why and how but not in a, see forskolin is bad sense (if that was your intention). There is data supporting forskolins effect on lipolysis and human in vivo data to support its use. There really isn't a question on how forskolin effects lipolysis, and this paper doesn't refute that.

 

[Jiigzz]

There's no dose because it is not an animal study...its just a petri dish study. So I would not worry especially since there are human studies on forskolin for fat loss. While looking at more petri dish studies, I think this one is more important that the one above:

http://www.ncbi.nlm.nih.gov/pubmed/6327383

Forskolin stimulation of thyroid secretion of T4 and T3.

Forskolin is a potent activator of adenylate cyclase in many tissues including the thyroid gland. We compared the effects of 10(-5) M forskolin and 100 mu units/ml TSH on the dynamics of T4 and T3 secretion from perfused dog thyroid lobes. Both agents induced pronounced increases in T4 and T3 secretion. The increase in secretion was significantly steeper during forskolin than during TSH stimulation. This may suggest that early processes such as TSH-receptor interaction and the subsequent activation of the catalytic unit of adenylate cyclase are of importance for the pattern of very gradual increase in hormone secretion during TSH stimulation of the thyroid. In other respects forskolin seems to induce absolute and relative secretion of T3 and T4 very similar to those obtained by cAMP and TSH.

Use Forskolin-95 to avoid the stomach issues commonly caused by low % extracts

Danke. Didnt look into it at all

Edit: the text means absolutely nothing to me lol

 

[Synapsin]

We can agree to disagree

Don't really understand how you can say that without elaborating further. A few people already elaborated on your first post as to why it is not applicable in humans and you haven't refuted any of it.

 

[mw1]

Use Forskolin-95 to avoid the stomach issues commonly caused by low % extracts

Tried and no difference

Same here...well kind of . With lower % extracts I got cramping but with higher it gave diarrhea

 

[furion]

Interesting paper, however any potential clinical significance pertains only to TSH effects on ATGL- and even then such in vitro results would normally preclude in vivo testing if there was scope for obtaining usable data, which in itself and my opinion, is not exactly dire. From a pathological perspective other complications of chronically elevated TSH would be much more acutely apparent than TG accumulation in adipose tissue and therefore would be appropriately treated prior to such becoming a concern. This essentially limits any potentially clinical implications of the findings of this study (and proceeding in vivo studies, if they are performed).
Additionally, from what I understand research is yet to completely elucidate mechanisms of intracellular triglyceride hydrolysis and there appears to be more lipase enzymes involved than simply ATGL and HSL. The study did not actually test for TG accumulation- so it is definitely far too premature to draw any sinister conclusions about forskolin from the results.

 

[Geoforce]

Same here...well kind of . With lower % extracts I got cramping but with higher it gave diarrhea

Personally I feel like this is a pretty big myth. It seems the vast majority of people get slight sides with forskolin no matter what the extract percentage. I get the squirts with any extract percentage.

 

[kissdadookie]

Personally I feel like this is a pretty big myth. It seems the vast majority of people get slight sides with forskolin no matter what the extract percentage. I get the squirts with any extract percentage.

Agreed. Maybe it's because most people are taking it with y and something that likely contains higenamine? Because that combo of stim clears out my gut right quick.

 

[Geoforce]

Agreed. Maybe it's because most people are taking it with y and something that likely contains higenamine? Because that combo of stim clears out my gut right quick.

I get it regardless of the other stuff I take. The idea that 95% extract=no stomach sides just doesn't jive with the huge amount of anecdotal evidence found on this forum.

I will say that my sides with Forskolin at any dosage tend to subside within a 2 week window.

 

[Jiigzz]

I get it regardless of the other stuff I take. The idea that 95% extract=no stomach sides just doesn't jive with the huge amount of anecdotal evidence found on this forum.

I will say that my sides with Forskolin at any dosage tend to subside within a 2 week window.

I agree. I've found no difference between extracts and IronFist (Neuron) has stated that Forskolin would cause GI distress regardless of % extract

Completely false. The higher % forskolin, the more likely GI effects will occur.

If a 95% forskolin extract does not cause increased motility/diarrhea, then it is bunk.

If you do not get the GI symptoms I mentioned earlier, then you are not consuming genuine forskolin. It's a pretty reliable litmus test, as forskolin has been used for decades as an artificial means of mimicking diarrhea-causing pathogens.

http://jn.nutrition.org/content/135/10/2320.long
http://clincancerres.aacrjournals.org/content/7/2/343.long
http://www.ncbi.nlm.nih.gov/pubmed/16112134
http://www.ncbi.nlm.nih.gov/pubmed/16061885
http://www.ncbi.nlm.nih.gov/pubmed/16614995
http://www.ncbi.nlm.nih.gov/pubmed/2311974
http://www.ncbi.nlm.nih.gov/pubmed/16495521
http://www.ncbi.nlm.nih.gov/pubmed/14684576
http://www.ncbi.nlm.nih.gov/pubmed/16455334
http://www.ncbi.nlm.nih.gov/pubmed/1329520

et cetra

Mr.Cooper explains that lower extracts might be even worse due to impurities:

Ironfist is quite right about the MOA by which forskolin can induce diarrhea. Anecdotally speaking, I think most would agree that an equivalent dose of forskolin, ingested as a low % extract vs a high % extract, produces different degrees of GI distress. This would most plausibly be due to other components found within the plant...the root is usually the specific site of extraction:

http://www.ncbi.nlm.nih.gov/pubmed/16468372

For more general info on forskolin's array of effects, here is a nice review:

http://www.altmedrev.com/publications/11/1/47.pdf

But that just shows that Forskolins MOA does cause GI distress BUT lower extracts may make it worse

 

[kissdadookie]

I get it regardless of the other stuff I take. The idea that 95% extract=no stomach sides just doesn't jive with the huge amount of anecdotal evidence found on this forum.

I will say that my sides with Forskolin at any dosage tend to subside within a 2 week window.

Never had issues taking it regardless of the concentration it's standardized for tbh.

 

[Geoforce]

Never had issues taking it regardless of the concentration it's standardized for tbh.

My sides aren't really bad, liquid when sitting on the ol throne.

I use 95% forsk a lot, but the only people I ever see talking about how it's better for the stomach are those who sell it. And we have had plenty of threads with people mentioning using 95% and getting sides so I hate to continue to see what I think is a marketing point pop up personally.

And again that is from someone who uses 95% forskolin all the time.

I don't think the brands of 95% forskolin I use are bunk though as all three I've used (Analyzed, Komodo, Reform all being Sabinsa licensed) have had the same motility issue

 

[kissdadookie]

My sides aren't really bad, liquid when sitting on the ol throne.

I use 95% forsk a lot, but the only people I ever see talking about how it's better for the stomach are those who sell it. And we have had plenty of threads with people mentioning using 95% and getting sides so I hate to continue to see what I think is a marketing point pop up personally.

And again that is from someone who uses 95% forskolin all the time.

I agree. I don't recall ever seeing any data suggesting that different concentrations would cause different levels of GI distress personally.

 

[mw1]

I get it regardless of the other stuff I take. The idea that 95% extract=no stomach sides just doesn't jive with the huge amount of anecdotal evidence found on this forum.

I will say that my sides with Forskolin at any dosage tend to subside within a 2 week window.

For myself the higher extract issues subside after about 10-14 days. With the lower extract the sides (cramps) last till about the 3rd or 4th day. If I'm mega dosing ( which I have done a couple times) it can more intense discomfort

 

[Danes]

I do have reflux and I am on PPI medication (esomeprazol such as nexium).
If i stop medication i get:
-upset stomach
-feel like upper part of the stomach is full
-no apetitte
-chestpain

So when I try Forskolin (no matter what %) i get the same symptoms like being withiut medication
I came across this one:
-forskolin increased HCL production in the stomach.
-Forskolin is a powerful stomach acid inductor hence it supports the hypothalamus/pituitary gland axis communication pathway which will result in the increased stomach acid production.

That explain my issues with Forskolin

 

[kissdadookie]

I do have reflux and I am on PPI medication (esomeprazol such as nexium).
If i stop medication i get:
-upset stomach
-feel like upper part of the stomach is full
-no apetitte
-chestpain

So when I try Forskolin (no matter what %) i get the same symptoms like being withiut medication
I came across this one:
-forskolin increased HCL production in the stomach.
-Forskolin is a powerful stomach acid inductor hence it supports the hypothalamus/pituitary gland axis communication pathway which will result in the increased stomach acid production.

That explain my issues with Forskolin

If that is the case, it would seem that the higher concentration extracts are probably going to be more problematic. A lower concentration extract may possibly be better as there are higher amounts of the other constituents of the plant being used?

 

[Danes]

If that is the case, it would seem that the higher concentration extracts are probably going to be more problematic. A lower concentration extract may possibly be better as there are higher amounts of the other constituents of the plant being used?

I was thinking the same thing!
Because we are talking aBout extract which increase HCL and not whole plant.
But 20% forskolin gave me the same problems. I gave up lol