Arthritis drug boosts fat-signaling and counters diabetes in obese mice

Scientists studying the activity of a drug used to treat rheumatoid arthritis have discovered it has some surprising functions, some of which may be useful when it comes to countering diabetes. The research, carried out on mouse models of type 2 diabetes, shows how the compound has dual potential to tackle inflammation linked to the condition, while also providing a metabolic boost that could help regulate appetite and promote healthy fat-signaling in obese subjects.

Led by researchers at the Baylor College of Medicine, the study stems from emerging knowledge around the role inflammation plays in insulin resistance, and how drugs that temper it might be against diabetes. A feature of type 2 diabetes, insulin resistance refers to the inability of cells to respond to the hormone and absorb glucose from the blood, and studies have established links between it and inflammation in white fat tissue.

To better understand these associations, the authors of the study sitted through a database of existing drugs in search of one that might affect both and diabetes.

“We computationally screened a small-molecule dataset and identified auranofin, an FDA-approved drug that has been used to treat rheumatoid arthritis, a condition involving inflammation,” said first and co-corresponding author Dr. Aaron R. Cox. “Auranofin exerts anti-inflammatory properties, which many people suspected would be beneficial in obesity and diabetes; however, nothing was really known about how it might affect metabolism.”

The scientists treated mouse models of diabetes with auranofin and closely examined the metabolic effects, with the animals made to consume a high-fat diet. One of the key findings centered on a hormone called leptin, which is produced by fat cells and signals to the brain that we are full. In obese subjects with more fat cells, leptin levels are heightened in a way that breaks down these communications with the brain, causing them to overeat through what’s known as leptin resistance.

Auranofin was found to reduce leptin levels in the obese mice. The drug also improved metabolic signaling in white fat tissue in a way that promotes a higher rate of lipid-burning, improved insulin sensitivity, and countered other obesity-related effects. Notably, however, it did so without altering the body composition of the mice.

“We discovered that auranofin has anti-inflammatory and anti-diabetic effects that are independent from each other,” said co-corresponding author Dr. Sean Hartig. “Auranofin improved insulin sensitivity, or the body’s ability to respond to insulin to keep blood sugar at healthy levels. The drug also normalized obesity-associated changes such as hyperinsulinemia – blood insulin levels that are higher than normal – in the mouse model. In addition, we found that auranofin accumulation in white adipose tissue reduced inflammatory responses without altering body composition in obese mice.”

The researchers note there is a lot more work to do before these promising results are translated into a clinical treatment, but are enthusiastic about their early findings.

The research was published in the journal Cell Metabolism.

Source: Baylor College of Medicine

Update: This story was updated on October 21 to clarify that the research focused on type 2 diabetes specifically.

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