Who you calling Fat

This week it seems that fat has taken NY by storm.

The May 6th Edition of the Science NY Times had an assortment of fascinating articles that related to fat in some way.

1. Study Finds That Fat Cells Die and Are Replaced
2. Evidence a High-Fat Diet Works to Treat Epilepsy
3. Its Poor Reputation Aside, Our Fat Is Doing Us a Favor (older - Aug 7, 2007)
4. Redefining Disease, Genes and All (separate topic - somewhat related)
   

1. It was previously thought that fat cells developed until puberty, at which point the sex hormones (estrogen) helped direct where in the body the fat deposits went. After puberty, aside from changes due to extreme circumstance (like liposuction), the number of fat cells remained the same. The cells got bigger or smaller as you gained or lost weight. It was even shown that after liposuction, your body somehow regenerated the same # of fat cells as prior to surgery (these new cells were super skinny).

New research is showing that 10% of your fat cells die and are replaced every year. Oddly enough, nuclear bomb testing helped move this stuff forward. The radioactivity released by above ground bombs created a spike in Carbon 14 isotopes in the atmosphere. C14 has 8 protons and 6 electrons (2 more than usual). The natural abundance of C14 in the atmosphere is one in a trillion, therefore, spikes in the atmosphere made an imprint in all things created at that time. The half life of C14 is 5700 years (long enough to not make a difference).

This principal was applied to the whole body, and showed that certain fat cells were very young.

2. A high fat diet showed itself effective in a randomized trial to decrease epilepsy seizures in children. This diet has been evaluated for a long time now. 38 % of kids had 50 % less seizures as compared to only 6% of kids in the control group. On a personal note, my professor and I researched the effects of a high ketone diet on seizure patterns in Mongolian Gerbils.

Ketosis is the state of metabolism when the liver uses fats (instead of glucose) for energy and converts fat into fatty bodies and ketones. Fatty tissue becomes an important source of energy and diet has to maximize fatty intake to maintain ketosis.

To review our basics, a fatty acid is a carbon chain (with double/triple bonds - unsaturated, no double/triple bonds - saturated). Fat tissue tends to be composed of three fatty acids bonded to a carbon backbone. Adipose cells store a lot of fat.

3. This article discusses the important benefits of our fat cells. They protect our organs (visceral fat), provide the bulk under the skin (subcutaneous), store an important energy source, and are critical to supplement disruptions in diet. In addition, these fat cells release different hormones. Too much fat causes a release of inflammatory hormones to decrease obesity, they also release leptin (a compound involved in reproduction). Clearly fat is no joke (line might be stolen from NY Times).

4. Everything is interconnected. Everything. Obesity, Epilepsy, Bipolar disorder, Chronic Fatigue Syndrome. Our gene make up is so complex that undoubtedly relationships can be found and made in disease never before associated by their outward symptoms.

Muscular Distrophy and Heart Attacks share a gene in common. Two genes connect diabetes and prostate cancer.

Nosology - the field of disease classification - is about to get its head knocked. For example, Jonathan Kerr and company [J Infect Dis. 2008 Apr 15;197(8):1171-1184] have published a study of a genomic signature of 55 patients with Chronic Fatigue Syndrome. 88 genes are up regulated. 6 of them have previously been targeted by drugs.

Looking at everything floods the blackboard with an assortment of random thoughts. Once a pattern can be elucidated, though, the most powerful answers can be found.

Ideas:

• Studies show that African Americans and Caucasian populations lose different types of adipose tissue during diet and tend to have different adipose tissue for the same body mass index . These two groups also have different insulin patterns and different diabetic profiles. Fat cells are created every year - can we direct them to different locations? Will they excrete different hormones more conductive to a proper glucose response? What effect will a high fat diet (ketosis) have on the diabetic population (I have a feeling it will be different for African American and Caucasian communities).
  
• Personal story, patient with Chronic Fatigue just started a south beach diet (avoid bad fats and sugars), feels great. How does all this fit in? Separately, if Chronic Fatigue Syndrome is characterized by some inflammation, might fat cells be involved?
  

I need a blackboard and more fat.

A joke at every end:

What do you call a fish with no eyes?
Fsh!

- better said then read [no i(s)]

Methotrexate - some thoughts

Today I wanted to write about a specific. It hasn't been in the news recently but caught my interest because it did something unexpected.

Methotrexate (shown at left) is a very interesting compound. Its history began with FDA approval in 1953 for oncology use.

It gets the job done by inhibiting folic acid breakdown.

Folic Acid or Folate is water soluble vitamin B9 (pictured right). [Note the similar structural elements of methotrexate and Folic Acid] Folic Acid is broken down to form tetrahydrofolate, a metabolite necessary for DNA synthesis, by the enzyme dihydrofolate reductase. Due to their similar structure, methotrexate can bind dihydrofolate reductase, block folic acid breakdown, and slow DNA synthesis. This is preferentially damaging cancer and immune system cells as they grow particularly fast and rely on DNA synthesis for their growth.

Methotrexate therefore has been used for chemotherapy (high dose) and as a treatment for inflammation associated with the autoimmune response (low dose).

A patient mentioned that Methotrexate relieved her symptoms of Fibromyalgia (a disease defined by chronic pain, abnormal pain processing, fatigue, brain fog, etc...). Why did this happen?

The etiology of fibromyalgia is still unknown. However, methotrexate has been used for a similar disease. Behçet's syndrome is characterized by generalized inflammation that causes ulcers, arthritus, and cardiac problems to a name some symptomes. Behçet's syndrome, like Fibromyalgia, is not well understood. The two diseases have overlapping symptoms of pain, fatigue and cognitive difficulties.

Something still doesn't add up. Methotrexate decreases inflammation and relieves symptoms associated with Behçet's syndrome and yet also pain associated with Fibromyalgia?.

Pain is caused by the activation of a nociceptor (pain receptor) by a mechanical or chemical stimuli. The message is passed by the nervous system through the spinal cord to the brain which responds by understanding the impulse as pain. Inflammation, among a variety of things, is known to cause the release of algesic substances which activate the nociceptors. The pictures comes full circle.

The overlap is there. A compound used for anti inflammatory disease helps with pain in disease states that are associated with inflammation. The difficulty is of course to really know whats happening. The woman who mentioned pain improvement was taking the methotrexate for retinal inflammation and happened to have fibromyalgia.

How do we make this connection faster? Is it smart to push for a clinical trial for methotrexate as a pain treatment when resources in the Fibromyalgia community are limited? Yet, it is these random observations that seem important. I guess thats why these are just some thoughts.

A joke at every end:

A blind man walks into a pharmacy with his guide dog.
He lifts his dog and starts spinning the dog by its leash.
A store employee runs up to the man and asks "hey, what are you doing?"
The blind man replies "just looking around."