In rapid growth since the 1970s, obesity will reach 1.12 billion people — 20% of the world's population — in 2030 if the rate of evolution continues. The projection, from the Global Burden of Obesity study," it's, the earth also points to 2.16 billion overweight women and men in the next decade. With a multifactorial cause and associated with diseases ranging from diabetes to different types of cancer, this condition, in short, reflects the imbalance between energy consumed and spent. But it's not a simple equation, easily solved with the old advice of "eat less and work out." more." It is already known that several factors contribute to hunger and fat metabolism. Among them, genetics. Although they are far from representing the silver bullet that will defeat obesity, studies on the influence of genes have gained prominence and space in scientific publications. The researchers expect that by identifying DNA mutations that, for example, make it difficult to feel full or burn stored energy, it will be possible to develop therapeutic approaches that, combined with lifestyle changes, promote healthy weight loss.
Studies of genetics associated with obesity have already yielded substantial results. For example, in 1994, scientists discovered the hormone leptin, which is involved, among other things, in feeling whole, nutrient absorption, and fat metabolism. Alterations in genes responsible for the brain's response to the production of this substance, especially one called ob, make caloric expenditure difficult while promoting excessive hunger. Research has shown that in people with hereditary obesity, the rarest type of the disease, leptin production is average, but polymorphisms (changes in the DNA sequence) prevent the brain from understanding this. He then keeps sending instructions to get more and more calories. This knowledge has led to the development of therapies for a tiny group of individuals with a hereditary form of obesity. The treatment does not work for the other types, but worldwide studies are being conducted based on this hormone and aimed at a wider public. At the same time, research teams are focusing on other genes, seeking yet another approach combined with traditional interventions. Last month, scientists at the University of Tartu, Estonia, discovered that a gene called NEGR1 could lead to prediabetes, especially in male animals. The absence of the protein stimulates weight gain and increased blood pressure in rats. Blood sugar levels, even on a fat-restricted diet.
Changes in this same protein are also associated with mental disorders, says Mari-Anne Philips, who led the study. Brain's conclusion can be said that it affects body weight, appetite, and mental health. Se,x hormones influence the effect of NEGR1 and, in the future, it is worth taking this protein into account in the diagnosis and prevention of disorders associated with this gene", she says. Appetite Also, in an animal model study, researchers at the Postgraduate University of the Okinawa Institute of Science and Technology (OIST) in Japan identified a protein that plays a crucial role in how the brain regulates appetite and metabolism. . According to the study published in the journal iScience, the loss of the XRN1 protein resulted in obese rats with an insatiable appetite. "Fundamentally, obesity is caused by an imbalance between food intake and energy expenditure," says Akiko Yanagiya, a researcher at the Cell Signal Unit at the OIST. "But we still understand very little about how appetite or metabolism is regulated by communication between the brain and parts of the body such as the pancreas, liver and fat tissues." In the study, the scientists bred mice that could not produce the XRN1 protein in a subset of neurons in the forebrain. This brain region includes the hypothalamus, an almond-sized structure that releases hormones into the body, helping to regulate body temperature, sleep, thirst, and hunger. At six weeks of age, the scientists noticed that mice lacking XRN1 in their brains began to gain weight rapidly and became obese around three months. There was an accumulation of fat in the mice's bodies, including adipose tissue and liver.
When the researchers monitored eating behavior, the team found that mice lacking XRN1 ate nearly twice as much per day as those in the control group. "This discovery was shocking," comments Shohei Takaoka, a Ph.D. student at the OIST Cell Signal Unit, who took part in the study. "When we first cleared XRN1 in the brain, we didn't know exactly what we would find, but this dramatic increase in appetite was very unexpected."didn't To investigate what might be causing the rats to overeat, the scientists measured levels of leptin in their blood. Compared to controls, the rate was abnormally high, making the animals stop feeling hungry. But the mice lacking XRN1 did not respond to the presence of the hormone. That is, they developed leptin resistance. Diabetes Scientists also found that five-week-old mice were resistant to insulin, a hormone released by the beta cells of the pancreas in response to the high blood glucose levels that occur after feeding. This type of failure in how the body responds to glucose and insulin can lead to diabetes. "We found that glucose and insulin levels increased due to the lack of response to leptin," explains Yanagiya. "Leptin resistance meant they kept eating, keeping their blood glucose high and therefore increasing their blood insulin." Another important finding was that the animals' metabolism was not able to expend energy. The researchers now intend to identify exactly how XRN1 impacts the activity of neurons in the hypothalamus to regulate appetite. "Identifying which neurons and proteins in the brain are involved in appetite regulation and fully determining how leptin resistance is caused can lead to a targeted treatment for obesity," says Yanagiya.
Relevant questions about genetics and obesity
Dr. Andrea Pereira, MD, Ph.D., clinical nutrition support physician and president of NGO Obesidade Brasil, answered these relevant questions about obesity genes.
What is already known about the interaction between genetic, environmental, and epigenetic factors in obesity? People with a strong genetic component have a different response to the "obesogenic" environment and may have a greater propensity for obesity, accounting for 25% of the Brazilian population. This appears in several studies with twins, showing inheritance of obesity ranging between 40% and 70%. Among the obesity of preferential genetic origin, since this disease is multifactorial, we have the Bardet–Biedl, and Prader–Willi syndromes. In addition to inherited obesity, which is rare, there is the most common category, polygenic obesity. It results from hundreds of polymorphisms (variations in the DNA sequence), each with a negligible effect. Both types of obesity are linked to brain mechanisms related to food intake, hunger, and satiety. Most studies demonstrate that genes related to leptin and melanocortin are associated with monogenic obesity.
How can knowledge about genetics and obesity help to review approaches to fighting the disease? Is it possible to also think about genetic-based prevention strategies? This growing knowledge about the genetics of obesity is essential for treatment and prevention strategies. However, they are still very experimental and linked to animal studies and have a very high cost. For now, the vast majority of these treatments are not reproducible in human beings, in addition to not being affordable for everyone.
Could genetic tests help choose the best treatment for the patient, or is it too early to think about it? It's still too early. Both are due to economic factors and the lack of representation in studies on human beings. It is always important to emphasize that we have several genes linked to various diseases. So even when these tests are recommended, we need to talk to a doctor to discuss which genes I need to be tested for. This will depend on the clinical examination and family history. Even genetic tests must be individualized, like any obesity treatment.
Resource: Correio Braziliense (5/12/2021)
Ana Paula Macedo
Comments