There are hundreds of genes that influence fat storage and metabolism. So, do we have any control over our weight? Here’s what experts have to say.
Sometimes it’s bad genes, not just a poor diet, that lead an individual to gain weight more easily than others.
Scientists have discovered that genetic mutations that cause a person to feel less full after eating may be more common than previously thought, leading those who carry these genetic variants to eat more frequently or consume more high-calorie foods.
“Obesity is not a choice,” says Giles Yeo, a geneticist who studies obesity at the University of Cambridge (UK). “The genetics of body weight are, by definition, the genetics of how our brain controls food.”
In Spain, 16.5% of men aged 18 and over and 15.5% of women are obese, according to the 2020 European Health Survey in Spain . But in the United States, the problem is even more pressing: almost a third of the adult population in the United States and almost one in six children and adolescents between the ages of two and 19 are currently overweight , according to the National Health and Nutrition Examination Survey.
For the two in five American adults who are obese, this excess weight increases the risk of developing many preventable diseases, such as type 2 diabetes, hypertension, stroke, cardiovascular disease, and certain cancers . But what is the cause of this epidemic? Is it lifestyle, or is our weight dictated by the genes we inherit?
Although diet and activity levels play a significant role in the rise of the obese population, science is revealing that, as with height, 50 to 80 percent of the variation in body weight can be attributed to subtle changes in a few genes . While single genetic mutations that make obesity inevitable are extremely rare, the hundreds of genetic variations that each have a minuscule effect (making some of us slightly more vulnerable to gaining weight) are more common. When someone inherits several of these variations, their risk of obesity increases significantly, especially when combined with other lifestyle factors.
“We need the public to understand that until now, and very incorrectly, we have viewed obesity as a character flaw,” says Naji Abumrad, an endocrine surgeon at Vanderbilt University Medical Center who treats morbidly obese patients and studies the effects of weight-loss surgery .
Obesity originates in the brain
That nature influences obesity was discovered by chance in 1949, when researchers at the Jackson Laboratory in Bar Harbor, USA, noticed that a strain of their laboratory mice grew abnormally “fat” because they ate a lot and seemed to be always hungry. It took them 45 years to identify a mutation in a gene ( called the obesity gene ) that caused the mice to overeat and gain weight. Soon, a series of studies showed that the obesity gene produced a hormone called leptin, named after the Greek word leptos, meaning “thin,” which bound to a receptor in the brain to signal satiety. Without enough leptin protein, the mice felt hungry, ate, and gained weight.
Subsequent studies revealed that the leptin gene was just one member of a complex network of genes linked together in the so-called melanocortin pathway (which also includes insulin) to control appetite.
“Leptin is the hormone produced in proportion to fat that tells the brain how much energy you have,” says Roger Cone, an obesity researcher at the University of Michigan’s Life Sciences Institute.
Fat cells secrete leptin into the bloodstream, which signals to the brain that they feel full and helps burn fat. “Just like a thermostat on the wall that controls the amount of energy in a room, the leptin-melanocortin system controls how much energy is stored as fat ,” Cone says. “ There are also other pathways that play critical roles in sensing leptin and converting that information into the amount of energy we burn and how much we acquire.”
From a few mutations to many variants
Forms of obesity caused by single-gene mutations, such as the one affecting the Jackson Labs mice, are estimated to be responsible for less than 7 percent of morbid obesity worldwide. Only about 6 percent of severely obese children have defects in single genes known to cause their disease.
According to Manfred James Müller, a nutritionist at Christian-Albrecht-University Kiel, Germany, these genetic mutations, which manifest at a young age, are very rare. For example, only a dozen cases of genetic leptin deficiency and 88 cases of leptin receptor deficiency have been diagnosed worldwide .
More common are alternative DNA sequences, called polymorphisms, which result in different versions of a gene that slightly affect its function.
To better understand the roots of complex traits, such as obesity, scientists use genome-wide association studies (GWAS) to identify gene variants linked to a specific disease.
“ We extract DNA from thousands, or even 100,000, individuals ,” explains Ruth Loos, director of the Genetics of Obesity and Related Metabolic Traits Program at the Icahn School of Medicine at Mount Sinai. Loos and her colleagues then compare the entire DNA set, or genome, of people who are obese with those who are not. The scientists then look for single-letter changes and calculate the likelihood that those variants are associated with obesity.
Intrigued to learn why only some people develop obesity, Christian Dina, a genetic epidemiologist at the University of Nantes in France, compared the sequences of 2,900 obese patients with those of 5,100 people of a healthy weight. Dina found that people with specific variations in a gene called FTO had a 22 percent higher risk of obesity. But figuring out why these genetic variants increase risk or how they work may take many more years of research.
For example, studies have shown that a different variant of the FTO gene that affects one in six adult European males can increase the risk of obesity by 70 percent . People with this obesity-risk FTO variant have higher levels of the hunger hormone ghrelin circulating in their blood, making them feel hungry soon after eating. Brain imaging studies of carriers of this genetic variant also reveal that these individuals respond differently to ghrelin and images of food.
For some, a ray of hope?
But not all genetic variants linked to obesity are bad. A rare genetic variant has also been discovered that may protect against obesity . A study of more than 640,000 people from Mexico, the US, and the UK found that those carrying an inactive copy of an active gene in the hypothalamus (which regulates hunger and metabolism) weighed about 5.3 kilos less and were half as likely to be obese as those with active versions.
“ But most studies linking obesity risk to genetic variations have so far been done in European, white populations,” Abumrad says. “ That means the findings may not be relevant to people of different ancestry .” The ambitious All of Us Research Program launched by the National Institutes of Health in 2018 (which plans to recruit at least 1 million people of diverse ethnicities) could help accurately assess the extent of the genetic predisposition to obesity .
Diet and lifestyle are the main drivers of the obesity epidemic, says Dina. ” But there’s a strong genetic basis for the difference in response to the obesogenic environment.”
The work of Dina, Yeo, and others is revealing that variations in many genes involved in our eating behavior can frequently be linked to a range of obesity traits, such as BMI, body fat percentage, blood leptin levels, and so on . So far, scientists have identified more than 1,000 genetic variants, each of which explains a very small part of the difference in body weight between individuals. Their association with an increased risk of obesity often becomes apparent later in life, as a result of an interaction between suspected risk genes and lifestyle variables, Müller explains.
Lifestyle remains the most influential factor in obesity cases.
However, the increasing trends in obesity worldwide have more to do with lifestyle choices , as there is no evidence of dramatic changes in the appearance of genetic variations from one generation to the next . In fact, studies have shown that the consumption of fried foods , along with underlying genetic background, plays a significant role in the development of obesity.
Although frequent consumption of high-calorie foods can cause people with obesity-associated genes to gain weight more quickly, awareness, prevention, and exercise are very effective in avoiding obesity.
” Having the same FTO allele as my father doesn’t mean I’ll become obese ,” Dina says. ” I have a slightly higher chance, but I can avoid it.”
Link: https://www.nationalgeographic.es/ciencia/2023/05/obesidad-genetica-implicacion
Authors:
By Sanjay Mishra
Date: Published May 10, 2023, 12:54 PM CEST
Note: The Nutrigenomics Institute is not responsible for the opinions expressed in this article.
PHOTO FROM PIXABAY.
