How much can we control our own weight?
A faulty gene affecting our brain’s circuits can impact on appetite making us feel hungry when we shouldn’t be, researchers have found.
Professor Sadaf Farooqi, Wellcome Trust Senior Clinical Fellow and Professor of Metabolism and Medicine at the University of Cambridge, has looked at the impact genes have on the regulation of our appetite and body weight.
How Do Genes Control Weight?
Our body weight is determined by the amount of energy or calories that we eat and the number of calories we burn up doing whatever we do in our everyday lives. Rather like these scales, if we eat more calories than we burn, we tip the balance the wrong way and put on weight.
In today’s world, we all have easy access to high fat and high calorie foods and many of us have a reduced need for physical exertion during our working and home lives. This can lead over a period of time to a gain in weight. So is it simply about eating too much food and taking too little exercise? And why do some people put on weight more easily than others?
We know that not everyone in the same environment will put on weight, so there must be something else involved? There is a lot of evidence to show that genes play a major role in determining our weight in the same way as they control the colour of our hair and eyes. We also know that weight problems can run in families.
Here in Cambridge, we have gone on to discover that sometimes being overweight from a very young age can be due to a faulty gene. This faulty gene may cause someone to always feel hungry, especially as a child. It may also affect the way calories are used up from the food we eat and cause excess calories to be stored as fat
Learn About Genes
I’m sure you have heard people say “it’s in your genes” as this is often how we explain the many different characteristics which make each and everyone one of us unique.
In fact, we all inherit two copies of every gene, one from our mother and one from our father. This means that members of the same family tend to be similar, as they are likely to have fewer differences in their genes.
How do genes work?
Our bodies are made up of many tiny units called cells each containing a complete copy of a person’s genes. We all have many thousands of genes and they contain the “genetic instructions” that we inherit from our parents. These “instructions” make us have blonde or dark hair, blue or brown eyes and even determine our body shape. They also control the way every cell in our body develops and grows and what it will do in our body, so they are very important!
Genes are made from a “chemical” called “DNA” (deoxyribonucleic acid) and are arranged in a specific sequence along very long thread-like structures of DNA called chromosomes, rather like a string of beads.
We all have approximately 30 to 40,000 genes stretched out along our DNA. Scientists have discovered what some of these genes do and how changes in these genes can cause particular disorders or diseases. There are however many genes which we still don’t know much about.
The genetic information in the DNA of our genes is in the form of a code and this is known as the “genetic code”.
How does the genetic code work?
It is all rather complicated. You need to think of the DNA being made of 2 strands of a mix of 4 different chemicals called “bases” which face each other and connect as pairs rather like the rungs of a ladder.
We use the first letter of each chemical as our code, so there is: Adenine, Thiamine, Cytosine and Guanine (ATCG). These 4 letters we will call “the DNA alphabet” and in the same way that letters of the alphabet combine to form words and sentences that mean something when we read them, the order of these chemicals are the “letters” which spell out the genetic code and the instructions to our bodies.
A single gene may be many thousands of letters long rather like the MC4R gene shown here.
What do these letters mean?
This is where it gets even more complicated. To be able to understand the code it needs to be read as “3 letter words” called “codons” and each set of 3 letters correspond to another chemical called an “amino acid”.
There are 20 different amino acids that can be made from the different word combinations and our bodies use them to make proteins, often referred to as the “building blocks” of our body. Many different proteins can be made such as keratin in our hair or haemoglobin in our blood to carry the oxygen that we breathe-in to all parts of our body.
So, genes are pieces of DNA that give instructions using chemically coded “messages” that can make proteins for our bodies to use. There may be hundreds, or even thousands, of three letter words in each gene message and sometimes things can go wrong.
What happens when there are changes in the genetic code?
If a single letter (base) in the sequence is out of place, a “spelling mistake” can occur. This can result in different “messages” that our bodies can’t understand, or a protein that doesn’t work properly or at all.
Individual letters or one or more whole words can be missing or even extra to what is required. In fact, even a whole gene can be missing!
As DNA passes from one generation to another through our genes, changes can happen to the code and these changes are known as “mutations”.
What is a mutation?
A mutation or faulty gene is a permanent change in a gene which may cause a problem with the development and functioning of many different parts of our body. Not all mutations cause problems.
A mutation can occur in several ways. Some faulty genes are inherited from our parents and may run in the family. Others can occur spontaneously and are called “de novo” mutations and may explain why a child can have a particular condition or disease even if there is no history of anyone else having the disease in the family.
The DNA code can also be changed by errors in the chromosomes.
What Genes Have We Found?
The first gene we found was the leptin gene in 1997. Children with a problem in the leptin gene put on weight very quickly and at a very early age.
The children are always hungry, never feel full and will seek out and ask for food even after they have just eaten. The reason for this continual drive to eat is because the children are lacking the hormone leptin which sends messages to the brain to tell us to stop eating because we are full. For these children, it has been possible to treat them with daily injections of the hormone leptin. The children are now normal weight, and it has also reversed a number of other problems that can be caused by the lack of leptin.
Leptin deficiency is very rare. We have now identified 11 other genes that can cause severe weight gain and we expect to find more with the new technologies that are now available to us.
We would, however, like to tell you a little bit about one of these genes called Melanocortin-4-Receptor (MC4R) because it is the commonest cause of severe weight problems in children. Many families with MC4R gene problems have very kindly come to Cambridge to help us with our studies and with their help we have learnt a lot about this gene. We know that the MC4R gene is involved in the same pathway in the brain as leptin, so children often feel hungry all the time. Children (and adults) are often very tall, and tests of body composition show an increase in bone and muscle mass compared to patients without this gene problem. We have also found that patients with an MC4R problem do not burn up the calories from food efficiently. One of the most important findings was that the MC4R gene is also involved in controlling blood pressure, something that will often be high in people that are overweight. We found that many of our MC4R patients had relatively normal blood pressures and we are looking into what this means for the heart.
For many of the gene problems that we have identified, including MC4R, there is no obvious treatment available immediately. In fact, finding the gene is the first step to understanding why someone is gaining weight and therefore finding the right treatment.
So do you guys think? how do you feel like genetics play a role in our appetite and obesity? Leave you interesting comments below and lets have a discussion.