Coconut fat (MCTs) downregulate PPAR gamma HER2 Upregulates

[R.B.]

Another snippet from my wanders.

MCT (three fats in on a chemical spine that look a bit like an E) are made from mid length fats which are found in coconut (and other things).

Reports have suggested MCTs help in weight loss.

PPARs work with fats to control metabolism and fat storage and probably lots else too.

PPAR gamma seems to be downgraded by MCTs.

Increased PPAR gamma is a factor in HER2 BC.

I have not found any trials with MCTs and BC which would answer the question does increased dietary MCTs reduce the risk of HER 2 BC.

It does raise more evidence as to the possible involvements of fats in HER2 risk factors.

There is lots on the web on MCTs. They are saturated generally and so some argue against them. They are also suggested to reduce bacterial infection.

If you do think about adding them to your diet, moderation is key and please talk to your advisor.


RB

http://www.obesityresearch.org/cgi/c.../full/11/6/734

Consistent with this prediction, we found that mRNA levels for PPAR{gamma}2 were substantially reduced in the adipose tissue of MCT-fed animals (Figure 4A)

http://clincancerres.aacrjournals.or...tract/9/8/3198

HER2 Regulation of Peroxisome Proliferator-activated Receptor {gamma} (PPAR{gamma}) Expression and Sensitivity of Breast Cancer Cells to PPAR{gamma} Ligand Therapy1
Zhibo Yang, Rozita Bagheri-Yarmand, Seetharaman Balasenthil, Gabriel Hortobagyi, Aysegul A. Sahin, Christopher J. Barnes and Rakesh Kumar2

Departments of Molecular and Cellular Oncology [Z. Y., R. B-Y., S. B., C. J. B., R. K.], Breast Medical Oncology [G. H.], and Pathology [A. A. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030


Conversely, down-regulation of HER2 by anti-HER2 monoclonal antibody Herceptin led to a decreased level of PPAR{gamma} protein and sensitization of breast cancer cells to the inhibitory effects of troglitazone. In summary, these findings show for the first time that HER2 up-regulates PPAR{gamma} expression and modulates the sensitivity of breast cancer cells to PPAR{gamma} ligand therapy.

[RobinP]

Rb, are you suggesting that something as simple as coconut may help decrease bc?

[R.B.]

Robin,

As many questions as answers. I have looked and not seen to date any trials directly looking at BC and coconut so I am simply raising a possibility.

I recently had a small but annoying problem with dry skin round the nose creases etc. I looked it up on the web and there was a suggestion it might have a fungal or bacterial base similar to "dandruff". Coconut is suggested as a bacterial agent and interestingly strong enough to for it to be suggested it assists in HIV, which would suggest it has more than minimal impact. I am very concious I have moved like many away from saturated fats and probably have a low intake. I would rather avoid steriod creams etc until all else is exhausted. I thought it worth a try and used coconut cream as a "lotion" and newly included some coconut milk and cream in my diet (not very much). It seems to have worked (which is not to say it could not have been something else that cleared the problem). I think coconut it may also have marginally increased my metabolism - the small of my back feels warmer - whichis interesting as well re weight loss claims.

There is nothing simple about fats. They are fundamental to a whole range of the body's functions as well as forming part of its structure.

Lots of trials suggest that diet can reduce the risk of BC and this is another part of diet.

Could Coconut help reduce risk of BC - from what I have read that is a possibility. Several factors add to a ghost of an image that it might. It has been reported on several occasions it assists with weight loss and does seem to moderate mechanisms in the area of weight, which all interconnect.

In very simplistic terms (that is as far as my understanding goes) tumours need to make or acquire fats to grow and the mechanisms they use to do so have some communality with those we use to store and make fats like FAS a mechanism used to make fatty acids from carbohydrates. FAS has been linked to HER2. One of herceptin's mechanisms is to intervene somehow in the fatty acid pathways.

I have not done a huge amount of reading on coconut and PPAR gamma so cannot be more definite, but on the grounds of assisting in weight loss, a suggestion that it helps improves the bodies bacterial resistance, and getting a variety of food it may be worth adding a small amount to widen ones diet, instead of other fats.

It is saturated so caution and moderation as well as the general prudent approach of keeping tabs on blood fats, keeping your doctor advised etc.

I will see what else I can find.

This trial below acknowledges the different impact of different types of fats, and suggested that MCTs in comparison to corn oils did not promote tumours in mice ( I do not know what type of cells OR what the MCT source used was - coconut has a very particular MCT profile and this is in mice)

http://www.positivehealth.com/permit...n/byrnes64.htm

" Coconut oil is another good example. Formerly used widely in baked goods, this oil is very rich in lauric acid. This fatty acid converts in the intestines into monolaurin, a powerful antifungal, antiviral and antibacterial substance. Coconut oil also contains caprylic acid, also a powerful antifungal. Recent research shows coconut oil to be stimulatory to the immune system and to offer substantial benefits to HIV+ individuals.19-21"

http://www.springerlink.com/content/47j8020n81267016/

"In addition, they indicate that MCT, due at least in part to their unique structural and physiological properties, exert markedly different effects on mammary tumor development than conventional long chain unsaturated fatty acids."

[RobinP]

Thanks for the links RB. I've never liked the idea of eating coconut due to the high fat content and calories. Now I'll rethink on that.

[RobinP]

After further research on PPAR, I realized it has major role in tissue repair and controlling inflammation at the same time PPAR oddly increase the 3PIK pathway and represses pTEN, which would seem to increase the inflammatory her2 pathway.

'PPARs are major regulators of lipid, glucose, and amino acid metabolism. Here we have presented some of their less well known functions in tissue protection and repair. A majority of the studies reviewed herein are descriptive, and even the use of specific ligands does not necessarily distinguish between PPAR isotypes or between PPAR-dependent and -independent mechanisms. However, collectively, the studies have improved our understanding of the role of PPARs in healing. Their actions are simultaneously systemic and cellular. Systemic effects are antiinflammatory, antioxidant, and metabolic, such as the normalization of circulating lipids and insulin resistance. During the early postinjury inflammatory phase, lipoxygenases and cyclooxygenases stimulate production of PPAR ligands. Indeed, perhaps the most striking action of PPARs is the control of inflammation, an event first observed 10 years ago (119). Inhibition of the NF-B pathway appears to be central to this process."

"Together, these results suggest that the PPAR and PPAR agonists already used in clinics may be harnessed for angiogenic diseases.^"
Quotes from:
http://www.jci.org/cgi/content/full/116/3/598?ck=nck

[R.B.]

Thanks for that Robin.

I have just skimmed the link. Good find 10/10 Well done - worth a skim even for those that do not have time to struggle with the technical just to get an idea as to how complex and interconnected all these conditions are.

Highly informative and food for a lot of thought. Much I simply do not understand but given the links with fats fascinating in scope impact and implication in the wider sense.

I had only seen PPARs material previously on lipids metabolism, from memory vascular disease, and hints of BC connections. (It is a while ago)

I will reread the link you found in more detail with interest.

Thank you again

RB

[RobinP]

I'm glad you like the find. I actually was researching about breast trauma and injury, causing bc as both my grandmother and I had a trauma to our breast about a year before we got bc. And well I found this article related for wound healing and PPAR.

It makes sense that the highest grade cancers are associated with EFGR where there is significant wound healing with angiogensis and PPAR to combat the high grade inflammatory process.

[Chelee]

Robin, I'm very interested in breast trama and cancer also. I found it very strange or just coincidence that the first time in my life I had a *terrible* fall on my right breast...then a week later I hit the exact same place that I fell on. I am talking serious injury...so painful. I was concerned. I've NEVER hit my breast in my entire life except those two times and both were within a weeks time and then about a month 1/2 later I find this BIG mass in my right breast? I've always wondered and done much searching on this subject. I'm glad to see I am not the only one.

Chelee

[RobinP]

HI Chelee, if you look at some of my old posts there is an article I posted about an association between injury and bc. There does seem to be some correlation. Your's happened really quick though after your injury. Maybe your breast was already in an atypical hyperplasia and this injury just tipped it all off to a malignant change.

[Chelee]

Robin, You have a good point, one that I had not thought about. That may very well be true that I already had the atypical hyperplasia going on at the same time? Very possible. I did always say that it might of been purely coincidence. It just popped up over night it *seemed* like. I will never know...but it sure made me wonder?

Thanks for letting me know about your posts on this subject...I am going to go check them out.

Chelee

[RobinP]

Some seek PPAR antagonist to control cancer as site in my above posted article. Whereas other researchers think PPAR may cause apotosis... It all depends on whether it is alpha or gama PPAR...

http://www.hindawi.com/GetArticle.as...155/2007/93416

[R.B.]

The PPARs are part of the fats pathways.

My head starts spinning when I try to get a hint of how it all fits. I really do struggle.

It does make it clear how complex and interrelated the bodies processes are.

There is an alpha, 2 gammas and a beta.

Here is a useful link. This is from someone looking at things from the perspective of obesity.

http://adipocyte.co.uk/PPAR.htm

And this is a ligand - two compatible chemicals in shape and from getting together for a while.

http://en.wikipedia.org/wiki/Ligand_%28biochemistry%29

Linoleic acid is a main ligand for PPAR aplha.

Basic Human Biology should be a compulsory subject at school. I did not do it. Would it have helped?

RB

[RobinP]

If Herceptin down regulates gama PPAR, as suggested by the first few article posts in this thread, then dietary supplements that downregulate the her2pathway would also decrease gama PPAR, such as green tea, GLA, ALA, DHA and EPA. It would appear that these natural inhibitors of gama PPAR would help block the her2 pathway. Of course, perhaps the beneficial alpha PPAR would be beneficial too. If so, perhaps natural supplements increasing alpha PPAR would have efficacy.

[R.B.]

Hi Robin still busy I see.

Thank you for your efforts. Posting here make me feel better by contributing.

The omega threes and particularly DHA down regulates PPAR gamma in some fat tissue.

There are fat storage cells in the breast I guess, to stabilise milk supply etc.

There must also be specific cells that make milk fats.

Whether PPAR gamma does the same thing in the breast cells I do not know. ONe of the many things I have not had the time to look at.