An increased activity of brown fat in mice lacking the USF1 gene protects them from both arterial disease and becoming overweight – a finding that might be translated into new treatments for diabetes and cardiovascular disease.
The results were reported by a Finnish team led by Pirkka-Pekka Laurila from the University of Helsinki in the journal Science Translational Medicine. The study was titled “USF1 deficiency activates brown adipose tissue and improves cardiometabolic health.”
In a press release, the research team described how they had initially intended to investigate the effects of the USF1 gene on blood lipid levels and cardiovascular health. Earlier studies have shown that the gene is associated with levels of cholesterol and blood fats (known as triglycerides) in humans.
The researchers created a mouse model lacking USF1 and noticed that the mice had low levels of triglycerides and high levels of “good” HDL-cholesterol in their blood. They observed that this was due to the fact that blood fat was more rapidly cleared from the circulation in the USF1 mutants compared to normal mice.
When the team submitted the genetically engineered mice to a high-fat diet, they saw that the mice stayed lean and healthy. Normal mice on the same diet, on the other hand, almost doubled their body weight, and had four times as many plaques in their aortas, a sign of atherosclerosis.
Researchers could exclude altered food intake or physical activity from the differences, since the mutant mice ate more and moved less than their normal counterparts. No difference in absorption of nutrients in the gut was found.
Instead, the scientists noticed that mice lacking USF1 had a higher metabolism, using more oxygen and producing more carbon dioxide. It turned out that the mice had an increased activity in their brown fat – a tissue normally used to protect the animals against cold. The USF1-deficient mice, however, used fat to generate heat both at room temperature and at 86 degrees Farenheit. In the process, fats and sugars from the circulation were cleared, protecting the animals against vascular disease.
To explore if these effects were also present in humans, the team analyzed data from the Finnish population, and found that individuals with a genetic variant giving rise to a less active USF1 had lower blood fat levels, better insulin sensitivity, and less plaques in their blood vessels than other people.
Based on the findings, the researchers concluded that inhibition of USF1 might be explored as a treatment strategy for diabetes and cardiovascular disease.
