Article by Dr Paul Batman PhD
There is a great deal of information written and communicated about obesity and its effects on our health. What is not so clear is information on the site where this complex disease initiates some of its problems.
What is an adipocyte?
The adipocyte or fat cell is the main type of cell in adipose tissue and is recognised as a critical player in obesity related cardiovascular disease.
An adipocyte is more than just storage for fat or adipose tissue, it is an intelligent cell that constantly monitors and changes the other molecules that are part of its structure.
The adipocyte is a tiny cell that is packed with triglycerides (stored fat) and occupies most of the cell. The cytoplasm, nucleus, mitochondria, endoplasmic reticulum and Golgi apparatus are pushed towards the edges of the cell.
All the adipocyte cell components are bounded by a cell membrane (covering) that permits the movement of molecules into and out of the cell, surveys the environment for danger, protects itself and has builder and scavenger molecules to maintain its order.
There are over 30 billion adipocytes in our body, which we carry as approximately 15kg of weight. It was originally designed as a small package of stored energy.
To give some idea of the size of an adipocyte, it weights about 0.5 of a micron compared to a teaspoon that can hold 6 million microns!!
Amazingly one gram of fat releases 9 Kcal of energy. This translates into approximately 135,000 Kcal of stored energy in our adipocytes, which would allow us to go without food for about 45-60 days.
As more food is taken in and not expended as energy the adipocyte increases in size (hypertrophy) and number (hyperplasia) to store more triglycerides.
As the energy imbalance increases it is accompanied by abnormalities in the adipocycte, particularly in two of its factories, the endoplasmic reticulum(ER) and mitochondria.
Where is the fat stored?
The ER is responsible for storing the fat, building proteins and sensing and regulating cholesterol. The proteins that are built in the ER must be folded correctly and then packaged in the Golgi Apparatus (GA) where they are stored for future use.
Normally as the amount of food we eat is increased, the endoplasmic reticulum (ER) in turn increases its ability to build proteins for the cell and surrounding structures and everything remains in balance.
What happens when we overeat?
However, an oversupply of food causes the adipocyte to increase in size and the Endoplasmic Reticulum (ER) becomes overwhelmed and begins to produce damaged proteins making them unable to fulfil their cell building and repairing role.
At the same time the ER’s ability to store fat and its cholesterol sensing ability is also adversely affected. The damaged proteins and excess nutrients build up in the cytosol (inside of cell) interfering with other functions of the cell.
To overcome this situation the adipocyte slows down the building of proteins and increases the clearance of the damaged proteins. If the ER and the cell cannot restore order the damage proteins die causing the ER additional stress.
At this point the ER releases free fatty acids and inflammatory molecules into the system to cope with their problem.
Once this occurs the result is an increase in fat and glucose concentrations throughout other cells in body as well as serious cellular insulin resistance, which can lead to hyperglycaemia (high blood sugar) and long-term diabetes. The insulin resistance extends to both liver and muscle cells.
What happens to the mitochondria?
In addition to the stress of the ER, hypertrophy of the adipocyte also creates oxidative stress in the mitochondria. Oxygen attempts to burn the fat in the mitochondria. The Mitochondria is the part of the fat cell that produces the energy and is regarded as the powerhouse of the cell.
When the excessive amounts of fat cannot be burned by oxygen in the mitochondria it causes a release of the immune cells that produce an inflammatory response. The inflammatory response causes the over production of free radicals and oxidative stress in the cell.
As the increase in free fatty acids build up the mitochondria has difficulty in processing the excess.
As the mitochondria become overworked and unable to process the excess fatty acids it produces an increase in reaction oxygen species (ROS) or free radicals that will ultimately impair mitochondrial function, which in turn creates more free radicals.
With obesity comes a depletion of antioxidant resources needed to neutralise the over production of free radicals. The production and release of key anti oxidant enzymes is severely depleted in obese people.
The increased oxidative stress causes damage to the adipocyte membrane, covers the membrane with a plastic coating and hinders the action of the mitochondria.
The uncontrolled oxidative stress changes the lining of the blood vessels and is the major contributor of cardiovascular disease and metabolic syndrome.
Next time you are offered that upsized meal remember where is might finally end up and the problems that overeating can lead too.