SREBP1

Hey, everyone!  I hope everything's going okay over on your end.  Over here, I'm just in pain from all the karate classes and hiking I've been doing (but it's okay, it's a good pain).

We're going to get into a topic that has been one of my biggest interests since we learned about it last year in biology.  It's an emerging field in the realm of genetics called "epigenetics," and it's just a fascinating subject to me.

Rewind back to the days of Charles Darwin, who documented and published a work called On the Origin of Species, which discussed his findings in the Galapagos Islands.  He noticed that different islands had species of birds with differently shaped beaks, and formed the earliest theory of evolution.

That one on the top left has seen things.

Skip forward a bit to Gregor Mendel.  He grew a lot of pea plants.  Like, a lot of pea plants.

This many.

After breeding plants with different traits together, he noticed certain patterns in the generations that proceeded the parent generations.

These variations.

This paved the route for a lot of our modern understanding of genetics--that our genes are set, and there's nothing we can do to change them.

OR CAN WE?

*dun dun dunnnnn*

That's where epigenetics comes in.  Basically, epigenetics says that, while you can't change your genes themselves, you can change how the genes are expressed.

DNA is wrapped around a molecule called a histone, like this:

Like a little spring!

This is mostly done to save space, since DNA is so long.  A lot of DNA doesn't code for anything, so it stays coiled up in histone groups that are methylated (which just means a methyl group is attached).  When it's time for DNA to be transcribed to make stuff, the histones become phosphorylated, which uncoils the DNA.

Epigenetics controls the coiling and uncoiling of the DNA wrapped around these histones.

Awesome!

Let's bring this back to what I've been studying.  There's a section of DNA that codes for the creation of Acetyl-CoA Carboxylase, which creates Malonyl-CoA (which inhibits fat mobilization into the mitochondria).  This gene starts transcription from the promoter gene SREBP1, which is actually called "sterol regulatory element-binding transcription factor 1," a name that I hope to never type ever again.

SREBP1 is turned on in the presence of insulin and glucose, which are in high supply in a person with diabetes.  Therefore, the cell keeps making Acetyl-CoA Carboxylase, which keeps making Malonyl-CoA, which is kind of causing the problem in the first place!

Fun fact: if you eat sugar, in about a minute, SREBP1 gets turned on, which inhibits the mobilization and use for fuel of fatty acids.

So, not eating a ton of sugar really affects things not only at a cellular level, but at a genetic level as well.  And if that's not cool, I don't know what is.

The Charlie Foundation

Today's Super Special Fun-Time Extraordinary Playtime Post is mostly going to be a plug for a website.  But it's a cool one, so I'm sure you can find it in your heart to forgive me.

Don't you?  Don't you?  Why are you ignoring me?!

 It's called the Charlie Foundation, and it actually has nothing to do with diabetes.

The Charlie Foundation was created because of a young boy named Charlie who suffered from epilepsy.  He was having multiple seizures a day for years until his doctors put him on a highly restrictive ketogenic diet.  His condition improved to the point where he was mostly seizure free, and the foundation was founded "to provide information about diet therapies for people with epilepsy, other neurological disorders and tumorous cancers."

While a lot of anecdotal evidence exists to verify this diet's treatment of epilepsy and other neurological disorders, no one is really sure why ketogenic diets work.  This is partly due to the fact that there are actually very few scientific studies that show what ketones actually do.

We know that they exist and do something.

There is a pretty good chance that ketones have a preservative (and possibly even regenerative) effect on brain tissue because of the success of ketogenic diets in managing epilepsy, as well as Alzheimer's and Parkinsons'.  The problem is that the body can only produce them by burning long chain fatty acids in the mitochondria, which can only get in if CPT1 is open.  CPT1 is closed in the presence of Malonyl-CoA, a byproduct of a glucose-heavy diet, aka a normal diet.  So, the body can't get ketones unless it burns its own fat.

OR CAN IT?

*cue dramatic music*

 Medium chain fatty acids, unlike long chain fatty acids, don't need to enter the mitochondria through CPT1, and can take a figurative back door in.  The oxidation of medium chain fatty acids still produces ketones, with the added bonus of not having to completely swear off sugar.  Medium chain fatty acids are found in things like coconut oil.

The source of all of life's joy.

Thanks for reading!