01 February 2008

The "Friendly" Marker so Inflammation and Obesity

The markers of chronic inflammation and obesity have a "tag you're it" kind of effect. The first marker to be "it" is TNF-a which in turn tags IL-6. IL-6 then induces CRP synthesis. Elevated blood concentrations of TNF-a, IL-6 and CRP indicate that there is an inflammatory condition occuring in your body which also stimulates obesity. The theory though, is that exercise and diet will reduce and perhaps eliminate the effects of TNF-a, IL-6, and CRP.

I read an article from the International Journal of Obesity that proves there is a decrease in CRP levels after significant weight loss following gastric banding. Exercise and diet will have similar effects as the gastric banding which proves that fat mass triggers the production of CRP. However, what was interesting, to me, was the fact that the TNF-a and IL-6 levels remained unchanged after the surgery. The authors speculate that there may be other mediators involved with the inflammation effect leading to obesity.

Laimer, M, et. al. "Markers of chronic inflammation and obesity: a prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention." International Journal of Obesity 26, 659-662. May 2002.
<http://www.nature.com/ijo/journal/v26/n5/full/0801970a.html.>

30 January 2008

Are Gastric Bands and Bypass Surgeries the Best Form of Metabolic Syndrome Relief...

... Although they do not directly treat the subclinical chronic inflammation which ultimately causes type II diabetes, hypertension, obesity, and dyslipidemia, many studies are showing that Stomach band surgery and Roux-en-Y gastric bypass result in remission of diabetes in a matter of months or even days. What at first seems like a safe "quick-fix" or weight loss fad being promoted by surgeons for its immediate results (for $17,000 to $30,000), may be a legitimate way to directly reduce excess caloric intake and result in glycemic improvement from weight loss, rather than altering insulin resistance or beta cell activity directly. This has shown to have high success rates, with low risk of complications due to surgery, while avoiding pharmacological strategies tampering with the complex relationships between the pancreas, liver, muscles, fat, gut, brain(hypothalamus), and even the skeleton(osteocalcin). Until biomarkers can be identified to predict early disturbances in insulin sensitivity, or the complex inflammation signaling pathways can be better understood, this may be the best current way to avoid the high costs associated with weight loss therapies. After all current lifestyle and pharmacological strategies usually result in small amounts of weight loss in diabetics.

Questions: What limitations should be considered regarding the patient before permitting this surgery... B.M.I. requirements, age, all other forms of lifestyle treatments must fail first.
Are gastric bands actually a better method than Roux-en-Y gastric bypass or biliopancreatic diversion?

Diabetic Inflammation

After reading the article about diabetes the one underlying theme was that of inflammation.  I know that the macrophages are responsible for inflammation but what i didn't get was what part of the body becomes inflamed.  Is there an typical area where inflammation occurs due to diabetes such as in the pancreatic beta cells, the liver or certain muscles or is just simply where the most adipocytes coalesce?

Inflammation in Obesity is Common Link Between Defects of Fatty Acid Metabolism and Insulin Resistance

In this article, Diabetes Type II induced inflammation is more closely examined for the particular pathway regarding Tumor Necrosis Factor alpha (TNFa), although it is important to remember that the relationship between Type II Diabetes and obesity is multi-faceted and not limited to one specific pathway (which makes it so difficult to understand). The basis of this particular pathway proceeds sort of like this: The excess caloric intake and reduced caloric expenditure of modern lifestyle has lead to an increasing rise in obesity, which is due to the rise in fatty acids in the body and thus an increase in adipocytes in which to store the fat. Unfortunately, adipocytes have proven to not be pure storage centers, but have in fact been shown to have significant endocrine and paracrine interaction with surrounding cells, including macrophages. By increasing the number of adipocytes in the body, an increase of macrophages will be recruited to the area and an increase in TNFa production will occur. This article describes how TNFa has been shown to have a variety of implications, including: inflammation (an important role of macrophages), decreased insulin-stimulated glucose disposal, increased insulin resistance, and an increase in protein phosphatase 2C (PP2C). PP2C inhibits another cytokine called AMP-activated phosphokinase (AMPK), which is responsible for helping to maintain proper metabolic balance. These effects all contribute to a decreased level of skeletal muscle fatty acid oxidation, which simply leads to an increase in fatty acid production and repeats the cycle.

Questions: 1)Why do you think macrophages (responsible for TNFa) would be recruited to the area of adipocytes in fat tissue to begin with? 2) Is this recruitment preventable? 3) How much of a real contribution does TNFa have in inducing the inflammatory response in obesity/type II diabetes?

28 January 2008

Inflammation: the link between insulin resistance, obesity and diabetes

I'm really interested in how Tumor Necrosis Factor alpha (TNF) is integrated in insulin resistance (Type II diabetes) and the inflammatory response. This article discusses the link between insulin resistance, obesity, and diabetes with TNF and other inflammatory proteins. Basically, TNF is released by a variety of tissues to include adipose tissue, which is concentrated in the obese. TNF works on the liver by promoting phosphorylation of the serine insulator substrate 1 and inhibits auto-phosphorylation of the tyrosine insulin receptor. This has been known to impair insulin signaling therefore resulting in insulin resistance i.e. type II diabetes. It was also interesting to see that TNF inhibitors have been used to treat insulin resistance but have proven unsuccessful...I wonder why? I think it's really interesting to see the biochemistry behind physiological mechanisms. To understand how a car works, you have to learn how the parts work. Good article. Enjoy:D
Inflammation: the link between insulin resistance, obesity and diabetes.
Dandona P, Aljada A, Bandyopadhyay A.

Pig Brain Aerosols

Workers at a meat packing plant whose job was to blow the brains out of pig heads with compressed air have developed what seems to be an inflammatory brain disease. It is likely in this case that the mechanism is immunological. Our brains are antigenic, but as long as we keep them in our head they do not stimulate the immune system. If brain is given by an immunizing route (injected, inhaled) it may stimulate an immune response, when then crosses into the intact brain and attacks it. A typical reference to the brain incident: here

Do you think the man's popcorn problem is also immunological?

27 January 2008

Inflammatory Popcorn!!

http://www.nytimes.com/2007/09/05/us/05popcorn.html

The above article is from the New York Times and might be interesting to all of us (It talks about inflammation and the person was diagnosed at National Jewish Hospital in Denver)!!

This article came out last year but it really does lead to some questions about our environment and inflammation. How much that we take for granted has serious effects on our health?

Dr. Cohen at the University of Colorado was telling me about a similar case, but where people were exposed to pig brains...if he's reading this, we would love to read about it!

"Surgery may cure diabetes in overweight"

In the article titled "Surgery may cure diabetes in overweight" (url: http://www.azcentral.com/news/articles/0123obesity-diabetes0123.html ) it states that a common procedure called stomach-band surgery may be an effective treatment for obese individuals with diabetes. According to the Centers for Disease Control (2003), diabetes and obesity are two prominent issues to be dealt with by the American population. More than 44 million are considered obese in the U.S., and 17 million have diabetes.
In the reported study, fifty-five diabetic and obese patients underwent stomach-band surgery. The majority of the participants experienced a remission in their diabetes (the report stated that most patients achieved normal blood tests, and most even stopped taking their diabetic drugs). As intelligent researchers and scientists, we should be skeptic of new treatments and take many issues into consideration.
For example, (1) do the benefits override the risks of stomach-band surgery? and (2) why could stomach-band surgery be more beneficial than other types of weight loss surgery?