These genes explain why obesity affects men and women differently

by time news

Obesity causes many health problems and worsens several chronic diseases, including type 2 diabetes and cardiovascular disease. However, some obese people are more susceptible to complications than others. Scientists have long been searching for obesity-related genes that predispose people to such conditions, but it has been difficult to zero in on hundreds of clues to identify genes that may increase risk.

In a new study published in “Nature Genetics,” researchers at the University of Chicago have analyzed the impact of a genetic variant associated with a higher waist-to-hip ratio, a measure of abdominal fat, which is necessary for the formation of fat cells in humans.

This variant is also associated with higher blood cholesterol and triglyceride levels in women, but not in men, and contributes to excessive fat accumulation as a result of diet in female, but not male, mice, suggesting that Similar genes could lead to different patterns of fat distribution and risk of obesity-related diseases for women.

“We think of obesity as a primary disease or a source of morbidity, but what obesity really does is that it favors the appearance of cardiovascular and metabolic diseases such as diabetes, heart attacks, and hypertension,” says Marcelo Nobrega, Professor of Human Genetics at UChicago and lead author of the study. “All of these are related, but the puzzling part is that not all obese people develop these types of complications.”

Why is fat distribution important?

The distribution of fat in the body seems to play an important role in the development of the disease. A greater amount of fat deposited in the abdomen and around vital organs has been linked to increased insulin resistance and inflammation, and predicts increased risk of cardiovascular disease, kidney failure, and stroke, while that of abdominal fat is It is measured by the waist-to-hip ratio, which divides a person’s waist measurement by the hip measurement. Ratios of .99 or less for men and .90 or less for women are considered healthy.

Nobrega’s team conducted several association studies across the transcriptoma to compare the genomes of hundreds of people to identify genes that are linked to obesity and a higher waist-to-hip ratio. The ratio is what’s called a sexually dimorphic trait, meaning it appears differently in males and females. Men and women naturally have different proportions, and the average man’s body shape is different from a woman’s.

The genetic analysis found 91 genes that help regulate fat distribution mainly in women. Most of the genetic variants associated with these genes do not alter the sequence of the genes that code for the proteins; instead, they occur in non-coding regions that are thought to control where and how much a gene is expressed.

Interestingly, most of these variants are found in a class of DNA elements called Alu repeats or retrotransposons, which are remnants of ancient viral infections that integrated into the human genome and maintain hundreds of thousands of copies today, constituting almost half of the non-coding human population.

“We once assumed that most of these were archaeological sites of battles that occurred in the past between our genome and that of viruses. But then, over the years, people began to realize that many of these DNA sequences that came from viruses had actually become functional in the human genome,” explains Nobrega.

jumping genes

So-called “jumping genes” may have fat distribution patterns connected in humans, with implications for metabolic health in women. Next, the researchers zeroed in on a gene called SNX10, which was more strongly associated with waist-to-hip ratio in women, but not in men. They found that SNX10 controls the ability of adipocytes, or fat cells, to accumulate lipids and fat stores. In a mouse model, when the researchers knocked out SNX10 in adipocytes, females did not become obese when fed a high-fat diet, whereas males were.

The team also searched the UK Biobank, a database containing more than 700,000 genomes, and found that SNX10 is not only associated with a higher waist-to-hip ratio in women, but is also associated with higher cholesterol and triglyceride levels, which are commonly reported. associated with cardiovascular diseases.

“We have now identified a gene, out of hundreds of genes that are involved in fat accumulation or obesity, that is most likely to cause complications of the disease and, interestingly, it does so mainly in women,” says Nobrega.

The next step, Nobrega said, is to dig deeper into the biology of SNX10 and other similar genes to understand how it has these effects on metabolism, and perhaps one day turn it into a target for treatment.

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