Obesity and the Flu

Obesity and the Flu (Total Health, Volume 27, No. 6)

This is a lay article that the Inflammation class read. It's a perfect example of a person (Dr.) using scare tactics to get his point across, and overall losing the reader as well as the point he was trying to make.
The article talks about "silent inflammation" which, when you do a search on it, a term made up by Dr. Sears of The Zone fame (and for a low low price, you can buy his book on how to reduce silent inflammation following his diet).

Overall the article just uses big words to try to establish the link between obesity and the incidence of getting the flu. It's possible that obese people may be more at risk (due to increased inflammatory cytokines-read the other posts), but there are other reasons as well, that were never covered in this article...including access to flu shots, proper hygiene, etc.

It's very interesting to read articles that are out in the general literature. It helps you understand where a large portion of the country is getting misleading information!! That's why a site like Inflammablog is so important...let's get the real information out there!!

Being Obese Without Having Diabetes or Metabolic Syndrome

In this week’s discussion the class is covering the topics of Obesity, Type 2 Diabetes, and Metabolic Syndrome based from the articles posted on the 495 website. An interesting point that reoccurs in all of the articles is about Insulin Resistance. The development of insulin resistance is not yet known. However, we know it is a precursor of type 2 diabetes and increases amongst the obese population. There are no genetic connections that can be determined yet about insulin resistance. Do you think that understanding the development of insulin resistance is the goal in helping eliminate and control Type 2 diabetes and metabolic syndrome amongst the obese population?

It appears that once scientists are able to fully understand the pathway of insulin resistance, a big advancement will be made in these three inflammatory diseases. Obesity, a state of chronic inflammation, is the root cause for these inflammatory diseases which links insulin resistance amongst them. Adipose tissue is now known as a major endocrine organ. Some of the chemicals excreted here adiponectin, leptin, TNF-a, resistin, IL-6, and CRP. These chemicals have a direct affect upon obesity, diabetes, and metabolic syndrome. The one process that seems to be interconnected amongst all of these is insulin resistance. Once this process is determined, doctors will be able to control the inflammation pathways that cause these diseases to get out of control. What I propose is that once the scientists and doctors figure out this pathway, they will be able to control diabetes, metabolic syndrome, as well as other inflammatory diseases amongst the obese. One will be able to be obese without these health concerns.

Metabolic Syndrome, Type 2 Diabetes and Inflammation.

The association between Metabolic Syndrome, Type 2 diabetes and Inflammation.
Diabetes is the seventh leading cause of death in the U.S. Even more shocking is the fact that 80% of those who develop type 2 diabetes are obese. Obesity is a factor that initiates a cascade of events such as insulin reistance, type 2 diabetes and inflammation. Studies have shown that abnormal cytokine production specifically over expression of cytokine tumour necrosis factor-alpha (TNF-alpha) leads to insulin resistance. Another name for insulin resistance is metabolic syndrome. Over expression of TNF-alpha is predominantly seen in the obese. In fact studies have shown that after weight loss TNF-alpha expression decreases which lowers insulin resistance.

TNF-alpha over expression causes metabolic syndrome. With the metabolic support not stable, insulin resistance occurs. Metabolic syndrome (insulin resistance) causes a decrease in glucose transport. High amounts of glucose and fatty acids build up in the bloodstream. Long lasting insulin resistance as described leads to type 2 diabetes. This state of insulin resistance not only leads to type 2 diabetes but it promotes inflammation. How does it promote inflammation? Well an adipose tissue hormone called leptin initiates inflammation. Stimulation of leptin is caused through over expression of TNF-alpha and interleukin-6. This is a key link between obesity, insulin resistance and inflammation. Since obesity and diabetes are proinflammatory states, the link to controlling inflammation is by reducing obesity.

Revised Story of the Contagious Tumor in Tasmanian Devils

(Normally we'd replace the original post with the revised version, but since most haven't yet had a chance to see the original I'll leave it up. This revision was made because comments indicated to me I hadn't be clear in what I wrote the first time.)

Tasmanian Devils are a fierce marsupial that live only on the southern Australian island of Tasmania. In recent years their population has been severely reduced by a dreadful invasive facial tumor that affects mostly males; the animals starve or choke to death, or are so weakened that they are killed by more-aggressive males.

All tumors in an individual are thought to start from one cell, though its descendants undergo repeated random mutations, some of which increase its invasiveness and survival ability. So when you look at the chromosomes in the cells of an individual’s tumor you see a characteristic pattern of chromosome breaks, recombinations, and deletions; a genetic fingerprint that distinguishes every individual tumor, even those of the same diagnostic type (that is, patient A’s melanoma has a distinct chromosome pattern from that of melanoma patient B.)

Drs. Pierce and Swift wanted to study the chromosomes of the Taz tumors to see if they could learn something about the origin of the disease. They trapped 11 animals, biopsied normal and tumor tissue, and looked at the chromosome picture, called a “karyotype.” The normal cells had 14 chromosomes each, XX or XY and 6 pairs of autosomes, the non-sex chromosomes.

But to their surprise, all the tumors had exactly the same, and a very abnormal karyotype: 13 chromosomes total, but neither copy of chromosome 2, no X, no Y, and 4 additional chromosomes which could not be definitively identified (mashups of pieces of the missing chromosomes?)

Statistically there is no chance at all that this characteristic, highly mutated pattern arose independently in 11 animals. So: In all 11 animals, this is one and the same tumor! In other words, it arose once in one (long dead) Taz, and he transmitted its actual cells to another Taz, and so on and on.

We usually think this is impossible: After all, if I try to transplant my (normal or cancer) cells to you your immune system would reject them, because the target for rejection is a group of cell surface molecules called MHC, and MHC is so variable that the chances of yours being the same as mine are less than one in a million.

But there can be someone whose tissues you accept without any problem: your identical twin, who has the same MHC. Is it possible that all the Taz’s are identical twins? Of course not, they are born to different parents. But is it possible that the Taz’s are so inbred that they are essentially all identical? After all, they are a small unique population on an island with no input of new genes from immigrants. Although Taz have not yet been typed at MHC, a colleague of Drs. Pearce and Swift told them that when he mixed T cells and other white blood cells from random members of the Taz population together in cell culture, there was no activation of T cells in any case. Whereas if I did the same between cells of the members of our classes, in every case (unless we had a pair of identical twins!) there would be vigorous activation of T cells as they recognized the foreignness (to them) of the other person’s MHC.

The conclusion then is that the Taz population has become highly inbred and are thus passing a tumor from individual to individual which, instead of being rejected as a foreign graft ("allograft"), grows without restraint until it kills the recipient.

You can image, too, that if an infection arose that could kill one Taz it would kill them all. This, we think, is why we’re so diverse at MHC, which controls the extent to which we make immune responses; if one individual is susceptible, others will be resistant.

A.-M. Pearse and K. Swift. Allograft theory: Transmission of devil facial-tumour disease. Nature 439, 549 (2 February 2006)

Contagious Cancer in Tasmanian Devils

The Tasmanian Devil (TD) is threatened by a dreadful outbreak of facial tumors, which grow rapidly and kill the animals as they become unable to defend themselves and feed. There are fears that the entire population of this unique fierce, wolf-like marsupial may be lost.

Drs. Pearse and Swift captured 11 animals and biopsied the tumors, as well as normal tissue. They first described the normal TD karyotype: 14 chromosomes (6 pairs of autosomes and XX or XY).

To their surprise, all the tumors had exactly the same, and a very abnormal karyotype: 13 chromosomes total, but neither copy of chromosome 2, no X, no Y, and 4 additional chromosomes which could not be definitively identified. One animal had an inversion marker in all his normal cells; it was not found in his tumor.

In humans, certain malignancies have a characteristic chromosome break or transposition, but in addition, each patient’s tumors acquires its own particular chromosomal abnormalities. Nothing remotely resembling the condition with the TD has ever been described.

Their conclusion is that all TD have the same tumor, which they are passing from animal to animal. Since they are highly aggressive, encounters often result in biting, and the most likely place for one to bite another would be on the face. It is at that time, probably, that tumor cells are transplanted from one to the other.

Why are the tumors not rejected by the recipient’s immune system? They point out that the TD population shows little genetic heterogeneity, as might be expected when all animals live in a small continuous area like the island of Tasmania. They are all, in other words, closely related.

A colleague of theirs has told them that when one-way MLRs are performed between random members of the TD population, almost no proliferation of T cells is seen is response to MHC on the other animal’s macrophages; just as you’d expect in an essentially-inbred population. So the tumor is not recognized as foreign…

This is about the most dramatic evidence I've seen in favor of being as diverse as possible at MHC loci.

A.-M. Pearse and K. Swift. Allograft theory: Transmission of devil facial-tumour disease. Nature 439, 549 (2 February 2006)