Fat!

One of the major health issues facing our world, the western world especially, is obesity. In fact, it is estimated that there are over 1.4 billion people overweight with over 500 million obese. These figures are expect to rise. In 1971, it was estimated that in North America, 14.5% of the population were obese. Now, the figure is over double at 30.9%. These figures were taken from the Biological Sciences Review article 'Lifestyle and Cardiovascular Disease', Volume 26, Number 2. Britain, despite it's small land mass, is considered the second 'fattest' country in the world - in reference to it's people that is. It is not only to do with the fact our country is now becoming overcrowded, our very habits, morals, behaviour and eating patterns have contributed to a dramatic increase in cases of obesity in the last couple of decades. To many people, carbohydrates contribute to the base of a diet. However in many cases an imbalance of this food group inevitably leads to weight gain and the formation of excess fat (adipose) tissue. How does this mechanism work? Well, central to this question is respiration, adipocytes (fat cells) and of course the different types of fat. Here, I want to explain how a weight gain is achieved, even right down to the molecular level.

Firstly, we need to understand that the molecule glucose makes up the vast majority of carbohydrate-based foods. Glucose is essential to our well being, in particular being vital to the function of our nervous system and our muscular system. It's uptake by our many billions of cells initiate the start of the production of the 'energy' molecule ATP, or Adenosine Triphosphate. It is a continuous process, however once our cells are content with the amount of glucose needed to produce ATP, glucose is transported and stored in various tissues of the body.

Adipocytes

Usually, glucose can be converted into glycogen via glycogenesis for "short-term" storage in muscles and the liver. Glycogen can be easily hydrolysed back into glucose for ease of access to body cells and tissues. However alternatively, glucose can be stored as part of fat molecules called triglycerides. These molecules comprise of a glycerol backbone with three attached hydrocarbon chains. These chains were originally carboxylic acids, better known as fatty acids - they take part in a condensation reaction to release three water molecules in forming a triglyceride. The main site in the body in which we would find triglycerides is in adipocytes. However triglycerides can also be utilised by muscle cells in the release of energy if needed. Fats are generally considered a second source of energy after carbohydrates. As well as the storage of glucose, triglycerides can also be formed from the digestion of fatty foods into the base components glycerol and fatty acids before subsequent absorption.

So how exactly is fat managed?

Well, to start with there are two different kinds of adipocytes, white and brown. It is important to distinguish between these two cell types as they have very contrasting roles. When fat is said to be 'stored', it is held within the white adipocytes of the body. When these cells are content with the amount of glucose needed to carry out respiration to yield the maximum number of ATP's, excess glucose is converted into fat here. The receptor that recognises this and promotes the storage of fat is called PPARγ. Conversely, brown adipocytes are considered extremely 'energy ineffecient', "burning" up triglycerides and storing very little, if any, of them. The result is that much heat is produced, a consequence of the many mitochondria this cell has. In fact, it has the most of any cell in the human body. This was once considered a survival mechanism for newborn infants as they had brown adipocytes in large numbers - the heat generated helps to protect the child from comparatively cold conditions to the womb. New research has found that adults posses these exact same cell types, 'roughly 60g in the neck region'. These cells adjust their calorie-burni ctivity in accordance with food intake and external temperature just to name a couple.

Now here is the intriguing part. Recent experiments in mice have shown that an increase in brown adipocytes 'help protect against diet-induced obesity and type 2 diabetes by preventing the build-up of triglycerides in other cell types, such as those in the liver and muscle'.

So what are the potentials of brown adipocytes?

In my view, adipocytes quite fasdcinate me now I've read a lot more into the subject. In cellular respiration, glucose is commonly processed through a series of step-by-step exothermic reactions. However in brown adipocytes, the stage that normally produces the largest number of ATP's is halted. It is known as oxidative phosphorylation. This means rather than using the energy released form the exothermic reactions to produce ATP, it is dissipated as heat energy - usually regardedas very inefficient!

Scientists have spent years of research trying to suggest new methods to combat the ever-pressing problem of obesity. Novel resserach into a particluar protein found in adipocytes called sirtuin has sparked a glimmer of hope. Sirtuin has been found to be associated with 'calorfic restriction' where life expectancy has increased with decreasing the number of calories in the diet gradually over a prolonged period of time. As sirtuin is commonly found in metabolising brown fat cells, there may be potential for sirtuin to be stimulated in white fat cells in combating weight gain. The experiments that scientists carried out confimred that with an increased presence of sirtuin, white fat cells started to show some of the characteristsc of brown fat cells, i.e. genes were becoming switched on that were analogous to brown fat cells. Parallel to this, other genes in the white fat cells were becoming switched off, again the same ones that are switched off in normal brown fat cells.

This phenomenal "growing" effect of white fat cells has significant potential. It is down to the protein sirtuin, how this works requires a little more understanding. Sirtuin is found to bind to the PPARγ receptor and modifies it. This receptor is found on the nucleus of white adipocytes. Therefore this receptor doesn't resume in normal function - instead it 'activates a transcription factor called Prdm16 that stwiches on a set of genes necessary for using up chemical energy to produce heat'.

Another plus side of the 'browning' of white adipocytes is that, in diabetic mice, their responsiveness  to insulin increased.

Is it all too good to be true? Well, not exactly. You see, sirtuin is found in many different types of cell throughout the body, not just adipocytes. This would imply that adjusting concentrations of sirtuin will have additional, even unwanted effects to the body. These problems will need to be investigated further by researchers in the future.


Credit to Joseph Robertson, who writes for the Biological Sciences Review (Volume 26, Number 2), for his article "Fighting the Flab" which was published.