Neues Buch von Barry Sears: Toxic Fat

[RuStra]

hallo Sears-Fans,

eben bekomme ich das neueste Buch von
Dr. Barry Sears: "Toxic Fat. When good fat turns bad.", über amazon zu bestellen.

Noch auf dem cover steht:

Some extra body fat can be good

Lean doesn't always mean healthy

Eating less, exercising more may not work

Obesity is cancer

( Einiges Körperfett kann gut sein - Schlank bedeutet nicht immer gesund - Weniger essen und mehr Sport funktioniert möglicherweise nicht - Fettleibigkeit ist Krebs )

Ich hoffe, dass sich doch einige das Buch anschaffen + lesen werden, sodass wir dann nach und nach die wichtigsten Erkenntnisse aus diesem Buch hier eingedeutscht bekanntmachen können.

grüsse aus HH,
Rudolf

[RuStra]

Dr. Barry Sears: "Toxic Fat. When good fat turns bad."

ich fang mal an, zwei hochinteressante Anhänge aus diesem buch erstmal abzutippen, dann können wir uns nach und nach an die übersetzung machen.
zuerst der Anhang zur Insulin-Resistenz, erster Teil

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APPENDIX F

Insulin Resistance: It All Starts in Your Adipose Tissue

I’ve found that surprisingly few physicians understand what insulin resistance means, let alone what causes it. In the simplest terms, it means that the signal insulin is trying to communicate is not getting through to its target cell. It’s like continually ringing a doorbell and not having anyone answer. As a result, blood glucose is not taken out of the bloodstream effectively. The pancreas compensates by producing more insulin (hyperinsulinenmia) to drive blood glucose by brute force into its target cell. This increased insulin in the bloodstream, when combined with a large excess of omega-6 fatty acids, will lead to excess production of arachidonic acid (AA), which means increased silent inflammation.

What causes insulin resistance in any cell is inflammation, and the prime suspect is the inflammatory cytokine called TNF alpha. TNF alpha is one of the inflammatory cytokines produced when nuclear transcription factor NF-kappaB is activated. When it was first discovered in the mid-1990s that TNF alpha was associated with insulin resistance, there was a great deal of interest until researchers found TNF alpha levels to be about the same in the blood of both diabetics and non-diabetics. Furthermore, injected antibodies to TNF alpha appeared to have little impact on insulin resistence. So there was a mystery of how TNF alpha could rise in different places in the body without being elevated in the bloodstream.

I believe the answer to this paradox lies in the metastatic spread of toxic fat. To understand how, you have to got back to find the primary cause of insulin resistance in other cells, and that means going back to the adipose tissue.

It is often assumed that insulin resistance is primarily a problem of the muscle cells, but in reality, all cells have insulin receptors. That’s why insulin resistance can be found in liver cells, brain cells, and even fat cells. And it is in the fat cells where I believe the story of insulin resistance really begins.

If you have healthy fat cells (good fat), excess AA can be stored in them, thus preventing adverse effects in other organs. It is only when the fat cells become progressively sicker (bad fat) and eventually die (due to AA toxicity) that AA begins leaking from your adipose tissue and starts to accelerate the development of the chronic disease often associated with obesity – this ist Toxic Fat Syndrome.

Although I discussed these concepts briefly earlier, it is worth the effort to understand the science behind not only why silent inflammation makes you fat but also how that increased fat can be a possible staging area for continued inflammatory assault on every organ in your body.

Adipose Tissue

Fat cells are highly specialized cells that collectively make up your adipose tissue, just like liver cells work together to form your liver. Your adipose tissue is the heaviest organ in your body (as if you couldn’t guess). More importantly, your adipose tissue is just as vital to your survival as any organ because it controls the flow of high-octane fuel (fat) to make adenosine triphosphate (ATP) as well as prevents lipotoxicity.

The two most important mechanisms to ensure survival are the ability to withstand the stress of starvation and the ability to respond to infection by microbial invaders. In lesser-developed species such as the fruit fly, all these functions are tied together in what is known as the fat body. This fat body senses energy and nutrient availability, controls the metabolism of those nutrients, and finally coordinates immununolgical responses with its tissue, the immune system, and the liver still retain their ancient genetic roots. That is why today there remains a strong communication link between inflammatory and metabolic signaling pathways.

Inflammatory Responses Mediated by Macrophages

Among the key cells in the inflammatory response are macrophages, which are derived from circulation white blood cells. Although white blood cells themselves are benign, once they are transformed into macrophages, they become killing machines. The primary signals that acitvate these white cells to become macrophages are a group of pro-inflammatory eicosanoids (leukotrienes) derived from AA. The leukotrienes also act as vasodilating agents that let the newly transformed macrophages escape from the bloodstream and enter into the lymphatic system so that they can circulate to the target site. The same leukotrienes act as chemical flares that lead the macrophages to the battlefield.

Once at the site of inflammation, the macrophages unleash a formidable arsenal of weapons, including free radicals and inflammatory cytokines, in the hopes of destroying any of the invading organisms. They then finish the battle by consuming the debris so that no further inflammatory signals remain. But the macrophages are called off their attack only by the signaling of various anti-inflammatory eicosanoids. The primary anti-inflammatory signals come from anti-inflammatory eicosanoids, such as lipoxins, epi-lipoxins, and resolvins, as well as other DGLA-derived eicosanoids. It ist only by shutting down the attack phase led by macrophages that cellular rejuvenation (healing) can begin to take place.

This tightly linked system of cellular destruction and cellular rejuvenation is the basis of wellness. The problem occurs when either the destruction phase is constantly turned on (as in silent inflammation), or the rejuvenation phase is not operating at peak efficiency. In either case, you age faster and develop chronic disease at an earlier age.
Circulating white blood cells are not the only source of macrophages. They can also be generated within the adipose tissue, one of the most concentrated sites of stem cells in the body. With the appropiate stimulus, they can be transformed into either new fat cells or new macrophages (remember the fat cells and immune cells share common genetic ancestors). More important, both fat cells and macrophages have another shared factor – the ability to bind and take up fatty acids.

Fat on Fire

It has always been amazing to me that with all the talk about obesity, how few times researchers have actually looked inside adipose tissue to see what’s going on. When they finally did in 2003, they found that up to 50 percent of the fat mass in genetically bred obese animals consisted of macrophages. This means only one thing: the fat was “on fire”, because when you find macrophages, you also find inflammation. Growing levels of silent inflammation in adipose tissue sets the stage for the adipose tissue starting the spread of inflammation throughout the body.

[RuStra]

Peroxisome und PPARs, besonders PPAR-gamma

hallo an alle, die von der Biologie des Krebses lernen wollen,

ich möchte hier auf die Peroxisomen hinweisen, Zell-Organellen, die im Zytoplasma herumschwimmen und aus der Zeit vor der Endosymbiose zur eukaryotischen Zellen stammen. Als sich Sauerstoff in der Atmosphäre sammelte, waren das die ersten Sauerstoff-Entgiftungs-Stationen, die abgeschottet hinter einer eigenen Zell-Membran ihr Werk verrichteten und immer noch verrichten. Dabei aber H2O2, Wasserstoffperoxid, produzieren, ein Gift, das nicht im Zytoplasma auftreten darf, weil es da wichtige Proteine usw. zerstören könnte.

Nun ja, dann kam die Endosymbiose oder Zellsymbiose, die Mitochondrien entstanden. Gleichwohl wurden die Peroxisomen beibehalten und heutzutage haben wir in allen eurakytotischen Zellen eine Zusammenarbeit vor allem zwischen Peroxisomen und Mitochondrien.
S. die Wiki-Links zu den Peroxisomen und PPARs.

Was das mit Krebs zu tun hat?

Krebsentstehung und vor allem Krebsausbreitung, Metastasierung wird begleitet und erst möglich gemacht durch inflammatorische Prozesse.
Mittlerweile ist anerkannt, dass die Inflammation die "andere Hälfte des Tumors" darstellt, ein Bild, das ich einem aktuellen Review aus der Zeitschrift nature entnehme. Auf dieses Review mit der Überschrift "Cancer-related inflammation", das im Juli 2008 erschienen ist, werde ich noch gesondert eingehen.

Jedenfalls ist es so, was wir schon länger wissen, dass ALLE Massnahmen, die Inflammation unten zu halten, gleichzeitig Massnahmen gg. Krebs + Metastasierung sind. Und so sollten wir neben den schon bekannten und oft diskutierten Dingen auch die PPARs (Peroxisom Proliferator Aktivierter Rezeptor)aufnehmen. Diese Rezeptoren sorgen, falls sie aktiviert werden, nicht nur für die Vermehrung von Peroxisomen im Zytosol, sondern auch z.B. für Inflammations-Hemmung.

Ich habe unten 2 Text-Stellen aus dem neuen Sears-Buch abgelegt, aus denen man ersehen kann, dass die Aktivierung des PPAR-gamma zur Produktion des anti-inflammatorischen IL-10 führt.

Fragt sich nun, wie PPAR-gamma zu aktivieren ist.

Grüsse,
Rudolf

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Hier die beiden Text-Stellen aus dem
schon zitierten Appendix F und
APPENDIX G
aus dem Sears-Buch (ein weiterer Appendix, der äusserst interessant ist und irgendwann sicher hier übersetzt vorliegen wird).


APPENDIX F

Insulin Resistance: It All Starts in Your Adipose Tissue

S. 290

Although it is the EPA in the fish oil that reduces inflammation in the fat cells and inhibits endocannaboids, the DHA is also important as it is an activator of PPAR-alpha, which increases the production of enzymes involved in beta-oxidation of fatty acids. At high enough concentrations, DHA helps you burn fat faster.


Nutrigenomics: How Diet Affects the Expression of Your Genes


APPENDIX G

S. 296

Just as NF-kappaB can turn on inflammation, another gene target can turn on anti-inflammation.
These are the transcription factors known as peroxisome proliferator activated receptors or PPAR for short.
One subset of these receptors is PPAR-gamma. Once activated, it goes into the DNA to cause the synthesis of anti-inflammatory proteins, such as interleukin-10. Activation of PPAR-gamma in the fat cells also induces the synthesis of the hormone adiponectin that reduces insulin resistance. That’s great news.

Unfortunately, the same gene products coming from the activation of PPAR-gamma also encourage production of new fat cells. But these new fat cells are healthy (good fat) and can encapsulate more arachidonic acid (AA), thus reducing the likelihood of Toxic Fat Syndrome. In essence, you get fatter but live longer (just like the fat rats who were consuming massive amount of the polyphenol resveratrol).

[RuStra]

Fragt sich nun, wie PPAR-gamma zu aktivieren ist.

Nun, das hatten wir ja schon - wer kennt nicht Actos oder Prof.Reichle?
Hier hatte ich im August zu den PPARs was zusammengestellt.

Actos ist ein PPAR-gamma-Agonist, man kann das bei Prof.Reichle auch hier
in seinem Papier nachlesen.

Interessant ist, dass es bei dem therapeutischen Ansatz an den PPARs, vor allem dem PPAR-gamma, nicht nur um Agonisten geht, sondern auch um Antagonisten.

in seinem Papier nachlesen. Im PubMed finde ich mit den Suchbegriffen

"Peroxisome proliferator-activated receptor prostate cancer"

einen freien full-text - ein aktuelles review mit dem Titel:

"Potential of Peroxisome Proliferator-Activated Receptor
Gamma Antagonist Compounds as Therapeutic Agents for
a Wide Range of Cancer Types"
also:

"PPAR-gamma-Antagonisten eignen sich als Therapeutika für eine grosse Breite von Krebs-Typen"

Hier ist das Papier als pdf runterladbar.

Viel Spaß beim Lesen,
Rudolf