Obesity seems to be a hot topic these days so I decided to write a short article on why people are overweight, even if they exercise. It is important to note that exercise by itself does not make people lose weight. You have to consume certain foods at the right time to help speed up the process of weight loss. Diabetes is a very popular topic because it affects hundreds of thousands of people across the world. It is a major precursor to myocardial infarction, diabetes, some cancers, stroke, osteoarthritis and cardiovascular disease; to name a few.
Type 1 Diabetes is said to be genetic and is passed on to you by your parents. Epigenetics is the study of changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which affects how cells read the genes. Epigenetic change is a regular occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Or, epigenetic change can have more damaging effects that can result in diseases like cancer. Therefore, epigenetics is the controlling mechanism behind how your genome is structured. Here is another way to look at it. "I like to eat ribs on a Saturday night with my friends who I love very much.”
The above sentence can be thought of as your genome but epigenetics is a slight variance based on behavioural and environmental external stimulus that changes the way the genome works. Epigenetics would change the sentence in the following way; “I like to eat ribs, on a Saturday night with my friends, who I love very much”
As you can see the commas change up the meaning slightly but the same letters are all present in the same order. So when these epigenetic “tags” are placed on the genome they are thought to be removed when the person dies. Research is starting to show that this does not happen fully and some “tags” actually stick around and cause damage to the baby. This is how Type 1 Diabetes is passed on.
But how does it work? I have written articles on diabetes before so I will give the simple version before going into more detail of the intracellular mechanisms. When you eat a simple sugar meal such as a chocolate bar the glucose goes right into the blood stream quicker due to the fact that the glucose monomers are smaller than that of a complex carbohydrate such as starch. This causes a rapid increase in blood glucose levels which normally should be around 60-100mg/dl fasting. Simple sugars actually are poisons to the body and will get inside capillaries, kidneys, retinas etc. and rot them out. This is why many diabetes patients who do not take care of their disease get leg amputations, blindness or kidney failure. To prevent this from happening after every time you eat a delicious chocolate, the body secretes a hormone called insulin from beta cells in the pancreas. Insulin is like a key and slides into specific receptors on the cell surface that allow the “doors” to open which causes glucose to rush into the cell and lowers blood glucose. Once inside the cell the glucose is sent to the mitochondria for energy metabolism. See my “sport nutrition” articles for more detail.
There is a signaling cascade pf - different proteins that are activated in a certain way in order to open the “door”. This door is called Glut 4 (Glucose Transporter 4)- why can’t all scientific names be that simple? Insulin binds to the outside of the cell which phosphorylates a series of proteins: IRS–>PI3K–>AKT PKB–>AS160–>GLUT4.
GLUT4 travels to the cell membrane and says “come on in, I do not want kidney failure, make yourself at home”. At least, this is what happens in a lean healthy individual. If you are unable to produce insulin then you are locked out of your cellular house. Generically what happens is that your beta cells that produce the insulin literally get tired and just are unable to keep up with the constant demand of simple sugars rushing into the body. The beta cells break down due to entropy which is the second law of thermodynamics. Paraphrased- all reactions cause an increase in disorder within a system.
Side note: This is why people die at all. If we could reverse entropy (disorder) then no one would die.
So the beta cells start to break down and it starts to look like dawn of the dead within the pancreas. Your body still sends insulin to the cell but it does not register because it is tired. The exact mechanism is not fully understood. This is called Insulin Resistance (IR). Once you are insulin resistant you are clinically diabetic. Your cells do not register the insulin and blood sugar stays elevated causing necrosis (death) of tissues. That is the basic mechanism of diabetes. It has been shown that increased fatty acids in the blood have a positive correlation with diabetes. Why?
Fat is stored in the cell as a triglyceride. Glycerol back bone and three fatty acid chains, sometimes straight (saturated) and crooked (unsaturated). Fatty acids are transported to the cell by Albumin (the protein in the white part of eggs). Once they get to the cell they are transported into the mitochondria by CPT1 (Carnitine Palmitoyltransferase 1) and then undergo beta oxidation where they are cleaved 2 carbons at a time creating acyl Coa and undergo beta oxidation and then transferred to the electron transport chain. Glycerol is broken down and put into glycolysis. Again for more detail go to my “sports nutrition” Series for a full explanation. Fatty acids are broken down one chain at a time, from Triglyceride to Diglyceride to Monoglyceride also refered to as TAG, DAG and MAG respectively. A ceramide is a a type of fat that was thought to play a structural role in the phospholipid bilayer (cell wall) but this is not 100% true and it is now shown that is indeed plays a role in cell signalling. Long chains of fatty acids such as LC Acyl Coa’s along with DAG’s and Ceramides actually block the cell signaling cascade that brings GLUT4 to the cell wall. LC Acyl Coa inhibits the phosphorylation of insulin against the cell wall which is the first step in the cascade. Dag’s block the IRS and Ceramides block the AKT PBK. This is the main reason why GLUT4 does not go to the cell wall instead of previously believed, reduction of insulin receptors. There are less insulin receptors but that is not the main reason.
This is important because if you were to try and cure diabetes and think, "lets just create more receptors.” Another simple way to think about it is that extra fat in the cell causes traffic jams and GLUT4 finds it hard to get to the cell surface fighting its way through the lipids. It has been shown that by decreasing the amount of fatty acids in the blood, insulin sensitivity goes up which means that your body reacts to the insulin sent from the beta cells rather than just ignoring it because it is tired. Kim (et al. 2000) showed that overweight individuals are unable to burn fat as quickly as lean individuals. Why? We are not 100% sure. There is something wrong with the mitochondria or there are not enough mitochondria due to less muscle mass. What about transporters? Could CPT1 be defective so fat simply does not get to the mitochondria to be burned?
Another study showed that yes indeed fatty acid transportation is decreased in obese individuals. Below is a study that shows that CPT1 transporter is not the big answer and that there is still unaccounted for oxidation decreases in obese individuals. Long chain fatty acids need CPT1 transporter to get in the mitochondria. Medium Chain Fatty Acids however are small enough that they do not need the transporter, so what is causing the still persistent decrease in oxidation?
Maybe there is less mitochondria as mentioned earlier? A smaller area of mitochondria is seen in obese individuals compared to lean. Not a huge difference however, but maybe it is enough to cause fat oxidation decrease. So let’s assume this is correct how do we fix this?
Exercise increases insulin sensitivity as well as a decrease in blood lipid levels. Everyone knows you must be on an exercise program while watching your calorie intake and consuming the right types and amounts of food. Let’s get a little more specific though. In the morning, if you have sugary food such as a muffin or toast with honey then you are increasing the blood glucose levels right at the start of your day. Your glucose levels spike and insulin rushes in to decrease the glucose before damage occurs. You do not want these spikes!! Instead you want to have a plateau of glucose in the blood by ingesting protein in the morning. It is often said that protein in the morning helps you lose weight. This is not because it increases muscle mass and causes your basal metabolic rate to increase. It is a small part but mostly this is because it causes your blood glucose levels to remain low so you are not hungry 2 hours later at 11am and force more food down your throat just so that you do not crash. No one wants to crash so we eat more to bring glucose levels back up and then the spiking starts, beta cells get upset, insulin resistance occurs, diabetes occurs, you become overweight because you do not burn as much fat and then you slowly develop cardiovascular diseases and die. Like I said in the protein article I wrote a while back, you can have lots of it and because it takes longer to break down your insulin will not be affected and you will be full longer and not eat as much.
One contradiction I should mention is that in athletes intramuscular triglycerides are much higher but they are not insulin resistant. This is because of the fat is oxidized much better for the above reasons then an obese individual. So Save yourself from an amputation, have protein in the morning and limit carbs to dinner.
Before I end this little article, I will talk again about fatty acid ingestion. There is a lot of talk about saturated vs. unsaturated fatty acids. Simply said, saturated fatty acids create a brick structure in your cell walls and do not allow your cell membrane to move very much which causes damage to the cell long term. Unsaturated Fatty acids are better because they are more like fluid and allow more mobility in the cell structure.
Omega 3’s (n-3 PUFAs) increase fatty acid breakdown and help prevent fatty acid synthesis. It is not quite known if fatty oxidation increases due to decreased amounts of DAG and Ceramide. PUFAs (n-3) helps to activate PPARs (Peroxisome Proliferator Activated Receptor) which increase gene expression in the genome. This is a complicated process but has to do with histones that have DNA wrapped around them. The more tightly they are wrapped the less gene expression occurs. Without getting into too much detail histones are Loosened allowing fat oxidation enzymes to be expressed more. It is shown that Omega 3 such as fish oils do help increase insulin sensitivity. Omega 6 is another PUFA and has been shown to decrease nerve pain in diabetic patients after a 6 month regular ingestion period. You do not have to get finicky with the different types of fatty acids. Have a balanced diet with all different kinds of fats but try to limit saturated fats.
Hope that clears up the physiological aspect of obesity. Conclusion: Protein in the morning, decreased ingestion of all types of food and exercise, all help to maintain the healthy state of the pancreas.
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