This Genetic Mutation Makes People Feel Full

The subjects in this study had been thin all their lives, and not because they had unusual metabolisms. They didn’t care much about food. Britain researchers have discovered a genetic alteration that mutes their appetite. The scientists’ study relied on data from the U.K. Biobank, which includes a half million people aged 40 to 69. Participants have provided DNA samples and medical records and have allowed researchers to track their health over years.

The study of the appetite-dulling mutation was led by Dr. Sadaf Farooqi, professor of metabolism and medicine at the University of Cambridge, and Nick Wareham, an epidemiologist at the university. The study drew on Dr. Farooqi’s research into a gene, MC4R. She has probed it for 20 years, but for the opposite reason: to understand why some people are overweight, not why some are thin. People with MC4R mutations tend to be obese. Researchers have recorded as many as 300 mutations in this gene, and they are the most common single-gene cause of obesity. The mutations destroy satiety, the feeling of fullness after a meal, Dr. Farooqi and her colleagues have found. Normally, when people eat a meal, the gene is switched on and sends a signal telling people they are full. Then the gene turns itself off. But some people carry a rare mutation in MC4R that prevents the gene from working. As a result, their bodies never get the signal that they have eaten enough. They always feel hungry and often are overweight. In the new study, Dr. Farooqi and her colleagues found that in some thin people, the MC4R gene is always turned on, instead of always off, because of different mutations involving a previously unknown metabolic pathway.

Article: https://www.nytimes.com/2019/04/18/health/genetics-weight-obesity.html

Related Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276379/ 

appetite mutation

In the New York Times, writer Gina Kolata discusses the new study that might have found a gene sequence that makes people not care much for food. She began her study off the notion that there are some people who just don't fixate over food.  Believe it or not there are some people who don't think about their next meal immediately after finishing their current one. The study has found a genetic alteration that suppresses appetite and also reduces their chance for diabetes and heart disease greatly.

The study included half a million people in the UK from the ages of 40-69 who provided DNA samples along with their medical records.  During this study, a second study on obesity was conducted and yielded the ability to help predict who is at a high risk of it even in early childhood.  The gene is called MC4R and has the ability to destroy satiety which is very alarming.  When you eat your body will signal a gene to tell you that you are hungry, but people with the MC4R mutation never get that signal keeping the gene always on and can continue eating which raises their chance for heart disease by 50%.

The gene can also be flipped in the other direction such as the gene being always off.  This can be found in roughly 6% of the population and causes the person to always feel full.  This is amazing that the gene can just flip causing two very different conditions.  I cant imagine not being hungry due to my love for food.  It would be interesting to see how we can control this mutation in the future.

Cilia in Neurons Linked to Obesity

       

        The article Primary Cilia in Neurons Linked to Obesity discusses a link between two gene variants and an increased risk of obesity and diabetes. On January 8 of this year, Nature Genetics reported that the proteins that are localized to cilia of neurons in the hypothalamus(a region of the forebrain that controls hunger and other homeostatic systems) control food intake in mice. Nature Genetics also published two human genetic studies tying variants of a neuronal ciliary gene, adenylyl cyclase 3, to an increase risk of developing obesity and diabetes. This research contributes significant information about the importance of cilia in the brain. The mouse experiment contributed a consensus that cilia in the brain are important for feeding behaviors and energy homeostasis. All 3 of the experiments show that cilia function can have important affects on the general population and not only in the instance of ciliopathies(uncommon diseases caused by mutations to the genes that affect primary cilia). A geneticist at the University of California, Christian Vaisse, states it was recently found that obesity in ciliopathies was linked to the function of primary cilia in neurons. Removal of primary cilia from all the neuron cause the adult mice to become obese.

       A mutation to the gene that codes for MC4R(melanocortin 4 receptor) is GPCR(G-protein coupled receptor) which is involved in regulating food intake is one of the lead genetic mutations that cause severe obesity. Vaisse and his colleagues also found that the MC4R has a very large amount of primary cilia in neurons in the hypothalamus except for the two mutation of the gene which prevent accumulation. These studies give us good insight on the importance and roles of primary cilia in the brain. Vaisse and his colleagues plan to continue studying genes that predispose humans to obesity and their cilia. The plan on using this information to eventually to formulate a medication that acts of primary cilia signaling in MC4R neurons and may help people with defects of this pathways. I think this is very useful information in the field and I am interested to see where the research is taken next.

Results of a Defect in the MC4R Gene

A study was conducted to link obese individuals with the MC4R gene. Obese individuals usually enjoy indulging in foods with high fat content. High fat content will lead to an excess in caloric intake which may lead to weight gain.A study was conducted with lean and obese individuals. However, some of the obese individuals possessed the defective MC4R gene. The individuals were taken to an open buffet. The buffet served chicken with similar tastes, but each entrée contained a different percentage of fat content. The result was that the obese individuals with the defective gene ate significantly more of the higher fat content chicken than the lean and obese individuals. The defect in the gene causes individuals to enjoy eating the higher fatty foods than an individual with an unaffected gene. Another experiment was conducted, but this time the test was sugar content. The obese individuals with the defective gene ate remarkably less of the higher sugar content in this desert. The lean and obese individuals liked the desert with the higher sugar content. The calories obtained per gram of fat is double the amount produced by carbohydrates and proteins. The individuals with the defective gene are preferring to eat foods with higher fat content which further allows for a problem with weight gain. This article was very interesting to read because obesity is such a big problem in this country. For many individuals it is difficult to lose weight and this gene is most likely the cause of the problem. It would be very interesting if the same gene in an unaffected individual was cloned and administered to the genome of an individual with the defective gene. It is possible that this would allow an obese individual with the defective gene to have less desire to eat such unhealthy, high fat content foods.