Genes That Predict Obesity Complications Differ Between Genders

Obesity causes many health problems and worsens several chronic illnesses, including type 2 diabetes and cardiovascular disease, however, some obese people are more susceptible to complications than others.

Scientists have long been searching for genes linked to obesity that predispose people to such conditions, but zooming in on hundreds of leads to identify genes that may increase risk has been difficult.

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Obesity is a condition where there is excess accumulation of body fat which poses a risk to the health of the individual. It can affect children and adults.

‘A gene called SNX10 that controls the ability of fat cells was most strongly associated with the waist-to-hip ratio in women but not in men.’

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In a new study published in Nature Genetics, researchers from the University of Chicago characterized the impact of a genetic variant associated with a higher waist-to-hip ratio, a measure of abdominal fat, that is necessary for the formation of fat cells in humans.

This variant is also associated with higher cholesterol and triglyceride blood levels in women, but not men, and it contributes to excess fat accumulation as the result of diet in female mice, but not males, suggesting that similar genes might lead to different patterns of fat distribution and obesity-related disease risk for women.

Why Distribution of Fat Matters in Obesity Complications

The distribution of fat in the body seems to play an important role in the development of disease. More fat deposited in the abdomen and around vital organs has been linked to increased insulin resistance and inflammation and predicts a higher risk of cardiovascular disease, kidney failure, and stroke.

The amount of abdominal fat is commonly measured by the waist-to-hip ratio, which divides a person’s waist measurement by their hip measurement. Ratios of 0.99 or lower for men and 0.90 or lower for women are considered healthy.

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In the new research, researchers compared the genomes of hundreds of individuals to identify genes that are linked with obesity and a higher waist-to-hip ratio. The ratio is what is called a sexually dimorphic trait, meaning that it appears differently in males and females. Men and women naturally have different ratios, and the silhouette of an average man’s body is different from that of a woman.

The genetic analysis found 91 genes that help regulate fat distribution primarily in women. Most of the genetic variants associated with these genes don’t alter the sequence of the genes that code for proteins.

Jumping Genes for Metabolic Health

These so-called “jumping genes” may have wired fat distribution patterns in humans, with implications for metabolic health in women. The researchers next focused on a gene called SNX10, which was most strongly associated with the waist-to-hip ratio in women but not in men.

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They found that SNX10 controls the ability of adipocytes, or fat cells, to accumulate lipids and fat deposits. In a mouse model, when the researchers knocked out SNX10 in the adipocytes, female mice did not become obese when fed a high-fat diet, while males did.

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

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The next step is to dig into the biology of SNX10 and other genes like it to understand how it has these effects on the metabolism, and perhaps one day make it a target for treatment. The road that led us to find SNX10 is a good way to identify other genes that are likely to be amenable to therapeutic development.

Source-Eurekalert