Diet: This is why some people cannot lose weight

Diet: This is why some people cannot lose weight

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Why do some people gain weight more easily?

Obesity and obesity continue to increase among people. This is associated with many serious illnesses and reduced life expectancy. However, some people generally just don't seem to have any problems with their weight. Are there genetic variants in humans that protect against obesity and its consequences? Researchers at the University of Cambridge wanted to answer this question in a study.

A recent study by the internationally highly recognized University of Cambridge has now found that some people carry special genetic variants that actually protect them against the development of obesity, type 2 diabetes and heart diseases. The results of the study were published in the English-language journal "Cell".

How does our genetics affect our weight?

In the UK alone, there are probably around four million people with said genetic variants, the researchers report. The discovery of these genetic variants could in the future contribute to the development of new drugs that help people lose weight. The study makes it clear that our genetics play an important role when it comes to obesity. Some people are just lucky with their genetics because their genes protect them from the development of obesity.

What is MC4R?

It has been known among experts for several years that genes can influence a person's weight. One of these genes that is known to play a key role in weight regulation is called MC4R. The so-called melanocortin-4 receptor (MC4R) belongs to the group of melanocortin receptors. This receptor acts like a switch in the brain that can suppress appetite. If there are genetic variants in humans that disrupt this receptor, those affected gain weight slightly. In their study, the researchers found that other genetic variants in the MC4R gene that increase the activity of this brain receptor can actually protect people from being overweight. This finding will hopefully lead to the development of new drugs that copy the protective effects of these genetic variants and thus contribute to weight loss or maintenance of a healthy weight.

Data from half a million people were analyzed

The team around the professors Sadaf Farooqi and Nick Wareham and Dr. Claudia Langenberg of the Wellcome Trust MRC Institute for Metabolic Sciences in Cambridge examined the MC4R gene in half a million British volunteers who participated in the so-called UK Biobank study. In doing so, they discovered 61 different naturally occurring genetic variants. While some of these genetic variants caused people to become obese, other variants offered protection against obesity and some of its dangerous consequences, such as type 2 diabetes and heart disease.

Obesity with the gene's function switched off?

Professor Farooqi's team tried to find out why and how certain genetic variants affect our risk of being overweight and obese. MC4R acts as a kind of switch in the brain that is supposed to make us stop eating after a meal. They found that MC4R gene variants associated with a higher risk of obesity stopped the function of the gene. However, if the variants offered protection from obesity, they left the gene on. About six percent of the participants carried genetic variants that caused the receptor to remain switched on. People with these variants seem to eat less, which could explain their lower weight. People with two copies of this particular variant (1 in every 1,000 people) were on average 2.5 kg lighter than people without these variants and were also 50 percent less likely to develop type 2 diabetes and heart disease.

Genetics can protect against obesity

"This study shows that genetics play an important role in why some people are obese - and that some people are lucky to have genes that protect them from obesity," said Professor Farooqi of the University's Metabolic Research Laboratories Cambridge in a press release. The current discovery complements the team's recent work, which has already shown that some slim people have a genetic advantage when it comes to maintaining their weight. However, the results do not mean that we have no influence on our weight if we pay attention to our calorie intake and healthy eating. Some people simply have a greater chance of developing weight problems, the study's authors explain.

Genetic variants for the development of drugs?

When the researchers examined the genetic variants in laboratory experiments in detail, they found that MC4R can send signals via a signaling pathway (beta-arrestin pathway) that was not previously associated with weight regulation. Genetic variants that preferentially sent signals through this route were those that promoted association with obesity protection and its complications, and were also associated with lower blood pressure. "An emerging concept is that genetic variants that protect against diseases can be used as models for the development of medicines that are more effective and safer," says study author Dr. Luca Lotta. "Our results could pave the way for a new generation of weight loss therapies that prefer to activate MC4R via the beta-arrestin route," added the expert. Genetic studies by thousands of people and a functional understanding of the mechanisms behind genetic protection variants could help develop a new generation of drugs for common diseases such as obesity and diabetes that affect millions of people worldwide. (as)

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