BAT, COX-2, and ArA (X-Factor)

[G.W. Hayduke]

Looking for contributing thoughts on a mechanism of fat loss wrt X-Factor. Is it in effect turning white adipose into brown adipose?

Consider:

Cyclooxygenase-2 Controls Energy Homeostasis in Mice by de Novo Recruitment of Brown Adipocytes

Obesity results from chronic energy surplus and excess lipid storage in white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) efficiently burns lipids through adaptive thermogenesis. Studying mouse models, we show that cyclooxygenase (COX)–2, a rate-limiting enzyme in prostaglandin (PG) synthesis, is a downstream effector of β-adrenergic signaling in WAT and is required for the induction of BAT in WAT depots. PG shifted the differentiation of defined mesenchymal progenitors toward a brown adipocyte phenotype. Overexpression of COX-2 in WAT induced de novo BAT recruitment in WAT, increased systemic energy expenditure, and protected mice against high-fat diet–induced obesity. Thus, COX-2 appears integral to de novo BAT recruitment, which suggests that the PG pathway regulates systemic energy homeostasis.

http://www.sciencemag.org/cgi/conten...cience.1186034

[in10city]

After reading that, making the extrapolation to humans from rodent BAT research is a bit of a stretch. Mice tend to maintain a lot of BAT while humans 'generally' don't but it still likely has some physiological significance under some conditions in humns. What they did was induce a two fold increase in intra-abdominal COX-2 mRNA using cold exposure and steady-state beta-adrenergic stimulation. The question would then be would any change in response to ArA even be phsiologically relevant.

Look into its [and n-6 PUFAs in general] affect on UCP-2 too. Here's one study I was refering to if you want to continue your research.
The Regulation of Uncoupling Protein-2 Gene Expression by n-6 Polyunsaturated Fatty Acids in Human Skeletal Muscle Cells Involves Multiple Pathways, Including the Nuclear Receptor Peroxisome Proliferator-activated Receptor beta

[NO HYPE]

Looking for contributing thoughts on a mechanism of fat loss wrt X-Factor.

Evidence has demonstrated that endothelial cells metabolize both endogenous and exogenous arachidonic acid to prostacyclin-12. PG12 is a potent lipolytic agent, and elicits potent vasodilation thereby inhibiting platelet aggregation via the stimulation of adenylate cyclase [AC]. Evidence has also demonstrated a positive relationship between lipolysis and AC activity. Additionally, exogenous arachidonic acid administration initiates elevations in cAMP levels, thereby leading to the activation of AMPK [which is required for maximal activation of lipolysis in adipocytes].

[G.W. Hayduke]

So, if we were to try to make a list of the ways in which ArA increases fat loss, would it look something like this:


PG12
-----AC

COX-2
-----WAT --> BAT

AMPK
cAMP
PPAR
UCP

I think you see where I'm going with this. Thoughts?

[G.W. Hayduke]

After reading that, making the extrapolation to humans from rodent BAT research is a bit of a stretch. Mice tend to maintain a lot of BAT while humans 'generally' don't but it still likely has some physiological significance under some conditions in humns. What they did was induce a two fold increase in intra-abdominal COX-2 mRNA using cold exposure and steady-state beta-adrenergic stimulation. The question would then be would any change in response to ArA even be phsiologically relevant.

Oh it's definitely a mile long stretch, no doubt. I was just offering it up in consideration of the idea that COX-2 can change WAT to BAT... perhaps effectively in humans (would be exceedingly useful since, as you mentioned, humans are mostly WAT).

[in10city]

Oh it's definitely a mile long stretch, no doubt. I was just offering it up in consideration of the idea that COX-2 can change WAT to BAT... perhaps effectively in humans (would be exceedingly useful since, as you mentioned, humans are mostly WAT).

WAT wasn't converted to BAT in this study. The COX-2/PGI2 pathway was implicated in being able to "turn on" existing BAT within WAT and in affecting which developmental lineage pathway "pre-adipocytes" within WAT went down - WAT vs. BAT. BAT is also found in WAT. There actually is some debate as to whether or not with BAT within WAT is from differentiation or from WAT to BAT transformation, but the current thought is that it's from differentiation during development & maturation.

[Big Poppa S]

Was just reading a little blurb about this research this morning, very interesting. Ever since my old Kinesiology classes I've always wondered whether it would be possible to increase levels of BAT in humans, or whether it would be possible to effectively "activate" the BAT that is already within the human body. I must admit over the years I definitely haven't researched this as much as I would have liked to but now with my fiancee being the clinical lead at an obesity management center we're definitely researching into more ways of combating obesity.

[GOTSPEED]

Was just reading a little blurb about this research this morning, very interesting. Ever since my old Kinesiology classes I've always wondered whether it would be possible to increase levels of BAT in humans, or whether it would be possible to effectively "activate" the BAT that is already within the human body. I must admit over the years I definitely haven't researched this as much as I would have liked to but now with my fiancee being the clinical lead at an obesity management center we're definitely researching into more ways of combating obesity.

Post the link to the blurb bro, I don't know what the hell BAT is.

[G.W. Hayduke]

Post the link to the blurb bro, I don't know what the hell BAT is.

brown adipose tissue

[Serpens Aeon]

Post the link to the blurb bro, I don't know what the hell BAT is.

It's mentioned, along with the other acronyms used in this thread, in the abstract of the study posted.

[Big Poppa S]

Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity.
Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ.

Department of Cellular and Structural Biology, the University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Abstract
Summary A worldwide increase in the incidence of obesity indicates the unsuccessful battle against this disorder. Obesity and the associated health problems urgently require effective strategies of treatment. The new discovery that a substantial amount of functional brown adipose tissue (BAT) is retained in adult humans provides a potential target for treatment of human obesity. BAT is active metabolically and disposes of extra energy via generation of heat through uncoupling oxidative phosphorylation in mitochondria. The physiology of BAT is readily regulated by melatonin, which not only increases recruitment of brown adipocytes but also elevates their metabolic activity in mammals. It is speculated that the hypertrophic effect and functional activation of BAT induced by melatonin may likely apply to the human. Thus, melatonin, a naturally occurring substance with no reported toxicity, may serve as a novel approach for treatment of obesity. Conversely, because of the availability of artificial light sources, excessive light exposure after darkness onset in modern societies should be considered a potential contributory factor to human obesity as light at night dramatically reduces endogenous melatonin production. In the current article, the potential associations of melatonin, BAT, obesity and the medical implications are discussed.

[robertmm94]

Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity.
Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ.

Department of Cellular and Structural Biology, the University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Abstract
Summary A worldwide increase in the incidence of obesity indicates the unsuccessful battle against this disorder. Obesity and the associated health problems urgently require effective strategies of treatment. The new discovery that a substantial amount of functional brown adipose tissue (BAT) is retained in adult humans provides a potential target for treatment of human obesity. BAT is active metabolically and disposes of extra energy via generation of heat through uncoupling oxidative phosphorylation in mitochondria. The physiology of BAT is readily regulated by melatonin, which not only increases recruitment of brown adipocytes but also elevates their metabolic activity in mammals. It is speculated that the hypertrophic effect and functional activation of BAT induced by melatonin may likely apply to the human. Thus, melatonin, a naturally occurring substance with no reported toxicity, may serve as a novel approach for treatment of obesity. Conversely, because of the availability of artificial light sources, excessive light exposure after darkness onset in modern societies should be considered a potential contributory factor to human obesity as light at night dramatically reduces endogenous melatonin production. In the current article, the potential associations of melatonin, BAT, obesity and the medical implications are discussed.

hmmmm. i have never heard anything about this before. very interesting. anyone ever seen any other studies on this?

[ss4vegeta1]

Subscribed.

[kfairhurst]

brown adipose tissue

Afaik, isn't BAT only present in children?

[PinchTheBear]

Afaik, isn't BAT only present in children?

Nope. It's present in adult humans, but scarcely. It's most abundant in hibernating mammals, but scarcity doesn't necessarily mean insignificance.

[kfairhurst]

Nope. It's present in adult humans, but scarcely. It's most abundant in hibernating mammals, but scarcity doesn't necessarily mean insignificance.

True, but if it isn't an active energy source wouldn't it be a safe bet to say it is likely that it wouldn't be affected by Ara?

[PinchTheBear]

True, but if it isn't an active energy source wouldn't it be a safe bet to say it is likely that it wouldn't be affected by Ara?

Its function isn't as an energy source in this case... actually, quite the opposite.

[kfairhurst]

Its function isn't as an energy source in this case... actually, quite the opposite.

That's sort of what I meant, I know it isn't a very active tissue in adults and that was more along the lines of what I was getting at. I haven't read much about it, just recall from one of Lyle McD's books.

[PinchTheBear]

That's sort of what I meant, I know it isn't a very active tissue in adults and that was more along the lines of what I was getting at. I haven't read much about it, just recall from one of Lyle McD's books.

I misread your post. Here: http://www.ncbi.nlm.nih.gov/pmc/arti...f/10620491.pdf

Also just peruse googlescholar for information on how ATP functions in lipogenesis and thermogenic energy equilibrium.

[kfairhurst]

I misread your post. Here: http://www.ncbi.nlm.nih.gov/pmc/arti...f/10620491.pdf

Also just peruse googlescholar for information on how ATP functions in lipogenesis and thermogenic energy equilibrium.

Thanks for the read. Curious about taking Ara on off days. It would still get used even once stored, but would the effect from taking it be worth it? You wouldn't be causing inflammation before ingesting, but the stored Ara could be used/released when exercising in future training sessions. Correct my flawed logic if you may

[PinchTheBear]

Thanks for the read. Curious about taking Ara on off days. It would still get used even once stored, but would the effect from taking it be worth it? You wouldn't be causing inflammation before ingesting, but the stored Ara could be used/released when exercising in future training sessions. Correct my flawed logic if you may

Fatty acid metabolism and PG synthesis (and subsequent activity in the body) is a 24 hour process at rest. There is no "loading" or "storage" period of concern. The goal is coupling the dose with a time during which its effects will be potentiated maximally, i.e., pre-exercise.

[kfairhurst]

Fatty acid metabolism and PG synthesis (and subsequent activity in the body) is a 24 hour process at rest. There is no "loading" or "storage" period of concern. The goal is coupling the dose with a time during which its effects will be potentiated maximally, i.e., pre-exercise.

I understand there is no loading, but if taken not pre-workout on an off day for example, would it not simply get stored? If it is stored, and energy use/storage is an ongoing process would it not just simply be released later and not wasted? I mean a muscle would stay inflamed more than a few hours pre-workout, would it be possible for the Ara to keep the inflammation longer/increase it when not used prior to exercise?

Not trying to argue, yet get a better understanding. I appreciate your feedback!

[PinchTheBear]

I understand there is no loading, but if taken not pre-workout on an off day for example, would it not simply get stored? If it is stored, and energy use/storage is an ongoing process would it not just simply be released later and not wasted? I mean a muscle would stay inflamed more than a few hours pre-workout, would it be possible for the Ara to keep the inflammation longer/increase it when not used prior to exercise?

Not trying to argue, yet get a better understanding. I appreciate your feedback!

It can be stored in muscle tissue as well as adipose. It's a fatty acid. Ingesting the supplement without optimizing delivery to skeletal muscle is essentially wasted, especially post-prandial when it is likely
to be stored as adipose.

[kfairhurst]

It can be stored in muscle tissue as well as adipose. It's a fatty acid. Ingesting the supplement without optimizing delivery to skeletal muscle is essentially wasted, especially post-prandial when it is likely
to be stored as adipose.

I understand the process behind its storage, but with lipolysis being a 24 hr process could the Ara not be used to keep the inflamed muscle tissue inflamed longer? Or would the effects be so slim that it would not be worthwhile?

[PinchTheBear]

I understand the process behind its storage, but with lipolysis being a 24 hr process could the Ara not be used to keep the inflamed muscle tissue inflamed longer? Or would the effects be so slim that it would not be worthwhile?

I'm really not sure what you're talking about. In adipose, it's not ArA anymore.

[JoeyV123]

XFA is legitimate, check out and follow my log..Will see my progress and results from ArA

http://forum.bodybuilding.com/showth...hp?t=129498713