Bile Bears....

I am a second year Molecular Pathology student.  Most of my research encompasses understanding the mechanisms of metabolic disease (and to a minor degree treatment).  I want to give you a brief view of my thesis project to this point...and also some of the research my lab has contributed to the scientific community. 
Let's say it's lunch time.  You eat a hardy meal from your fav restaurant and begin your retreat back to finish up your afternoon work.  During that retreat and the remainder of your work day, your body's digestive system is active and ready to break down your meal to provide your tissues with nutrients and energy.  After your meal survives the acidic chyme of the stomach, it makes its way to the small intestine.  The intestine is divided into three parts: the duodenum, the jejenum (both of which includes the proximal & middle of the small intestine) and the ileum (which includes distal).  The small intestine is a rather large organ...~22-23 ft to be exact lol.  The length of the organ accounts for its high efficiency in digesting certain metabolic material.  Within the small intestine tissue, there are walls of muscles and nerves (parasympathetic and sympathetic) to help with movement of material. There are also small projections known as villi and microvilli which account for an increase in surface area and absorption. 
You're probably asking...when is she going to get to the point lol.  Let's start with some of the basics...there are enzymes that allow for the digestion of carbohydrates, proteins...*pause*
But what exactly digests fat?  I'm sure most of you know the answer to this...it's bile.  Bile is composed of bile acids and that are made by the liver and stored in the gall bladder.  During the digestion of your meal, bile was released into the proximal end of the intestine to begin the process of fat emulsification.  After the bile has done its job, it's recycled back to the gallbladder...you're probably wondering how this is done...
Once the bile or bile acids (BA) reaches the ileum of the intestine, it encounters several cell transporters...the apical sodium dependent bile acid transporter (ASBT) and the organic solute transporter alpha/beta (Osta/b).  These guys allow the BA to be recycled back to the gallbladder.  ASBT is located on the apical (facing the lumen of the gut) side of the ileocyte.  It allows for the BA to be imported into the cell.  Osta/b is located on the basolateral (facing the bloodstream) side of the ileocyte and allows for the BA to enter into the blood.  Once the BA reaches the blood, it travels through the portal vein and makes its way back to the liver where it's sorted back to the gallbladder.  The process of bile acid recycling is known as enterohepatic circulation (EC).  Blocking enterohepatic circulation can result in a multitude of things.  I'm going to mention briefly how you can block circulation and the effects of blockage.  I'll go into more detail about the molecular mechanisms involved with EC in future blogs.  So let's think about this elaborate circulation...there must be mechanisms in place to control it...right?  Well if you were pondering this, your mind is rotating on all cylinders.  Control of EC involves a lot of complex mechanisms...so I'll return back to this later.  But let's get down to the blockage.  The major way of blockage includes enzymatic inhibition of transport (or the transporters) of BA...that's right ASBT and Osta/b inhibition.  There are many levels on which blockage can occur, but I think focusing on transport is the key to understanding the lab's research and the mechanisms.  ASBT inhibition results in the gene expression of an enzyme known as Cyp7a1.  Cyp7a1 is the rate limiting gene involved with the oxidation of cholesterol into BA.  You're probably thinking where did cholesterol come from...well...many of the metabolic pathways within the body are connected; this includes cholesterol, bile acid, and glucose metabolism.  One of the ways the body gets rid of cholesterol is by transforming it into BA.  Osta/b inhibition results in the opposite...repression of Cyp7a1.  This is done through the activation of the BA nuclear receptor FXR and expression of the intestinal protein FGF19.  Therapeutic mechanisms to inhibit ASBT specifically, are being used clinically to lower cholesterol (the "bad" cholesterol LDL) levels.  Wooo!  That was a mouthful!  Now that the basics are out of the way, I think we can continue on to the molecular side of things with the next blog.  

Note: The title of  this blog relates to the usage of bears to harvest large amounts of Ursodeoxycholic acid, a secondary BA.


   

I'm going to take a new direction with this blog. I want to dedicate my postings to sound scientific ideas and research. 

The Scorpio Woman
A Scorpio woman is one of mystery -- part tomboy, part femme fatale. She has a provocative magnetism. She is maternal, not smothering. Whether she has a satisfying career or family life -- or both -- she gives everything. She can be demanding but is equally demanding of herself. Always looking to transform herself for the better, she never seems to age but grows in wisdom and maturity.

:-)
http://tlc.howstuffworks.com/family/scorpio.htm

Change

As humans, it's natural to fear change.  It's natural to defer transformation for instant gratification and satisfaction...we're impatient beings. 
Fear is an emotion perceived as a weakness...an Achilles heal.  But fear is what makes us human; so we can not turn away from that which is integrated within us. So what do we do?  We've reached an impasse.  We can either remain on the course or veer off into the wild distance...CHANGE.
The most unnatural feeling is to not expect change.  Logically, we grow from babies to children to adults...changing in physical as well as mental features.  Change is necessary for the progression of man.  It's the foundation of evolution and Darwinism.
I have to be honest.  I was afraid of change.  Afraid of its implications.  What would it all mean for me to change?  When I say change, I'm not referring to wardrobe.  I enjoy my jeans and my comfortable converse! lol  When I say change, I speak of a mental and physical transformation towards something greater.  I used to think this wasn't possible...but now I realize it's beyond possible...and powerful.  How do I know?  Because it's happening to me as I speak.
Everyday, I'm realizing what it takes to become a more complete individual: mind, body, and soul.  Some times I get scared...but I realize that the ultimate goal...the final me... will be something spectacular!
If you remember nothing from this short blog, remember this: you are human!  You were born to change, to transform.  Embrace it and love every horrendous minute of the journey. :-)