ADELAIDE, Australia—Australian scientists have discovered that a gene previously thought to play a benign role in humans is actually a major trigger for obesity and type 2 diabetes. Researchers are optimistic that their new understanding of the gene known as MNK could lead to new drugs that target the gene and prevent or treat two disorders, which together affect billions of people and pose major public health challenges throughout the world.
Studies at the South Australian Health and Medical Research Institute (SAHMRI) compared mice missing the MNK gene with normal mice that had the gene, which is commonly found in livers, fatty tissue and muscles. Both groups of mice were fed a high-fat diet, and the two groups reacted very differently. Among the mice with MNK, researchers observed high levels of body fat, diabetes and inflammation of fat tissue. The mice without MNK were free of these characteristics, which are all associated with obesity in both mice and humans.
SAHMRI professor Chris Proud, the lead researcher of the studies, said that his team still needs to gain a fuller understanding of the mechanism through which MNK affects weight gain and obesity. They believe, however, that MNK is directly related to the inflammation of fat tissue that is typically associated with obesity. Such inflammation is typically a root cause of the other adverse effects that stem from obesity, including cardiovascular disease and diabetes. In the case of diabetes, inflammation interferes with the normal action of insulin in the body.
“We’re interested in whether MNK plays a role in creating new fat cells, or expanding fat cells that already exist,” Proud noted in a statement released by SAHMRI. “We’re conducting more experiments with mice and fat cells in culture for quicker progress.”
Proud says his team of researchers began to study MNK after noticing particularly high levels of MNK in fat cells and in liver and muscle—tissues that play important roles in obesity and type 2 diabetes. The links between obesity and type 2 diabetes have long been a central focus of Proud’s research.
As he told The Advertiser, a South Australian news publication, “We had no idea [the genes] were involved in obesity and type-2 diabetes. Normally they are not doing anything bad ... but testing in animal models found they were crucial to weight gain when a high-fat diet was consumed.”
The researchers at SAHMRI are already anticipating the potential for their discovery to lead to new treatments. One challenge they face is that MNK cannot be removed from humans as it was in the mice that researchers used for their study. The likely alternative to deleting the gene would be to use a drug to block its function. Proud’s researcher team plans to launch further studies to explore the therapeutic potential for such a drug in humans.
Proud has applied for an Australian patent to protect the therapeutic applications of MNK, and he is considering taking steps in North America and Europe to pave the way for development of any drugs that follow from his research. “We’re working with local colleagues at University of South Australia, and others in the United Kingdom, Singapore and perhaps China for drug development,” he noted.
SAHMRI is a medical research institute that was launched in 2009 by the South Australian government in Adelaide, South Australia. The institute focuses its research on several themes, and Proud is “theme leader” for the the Nutrition and Metabolism division.
In other recent SAHMRI news over the summer related to obesity, it was noted that University of Adelaide researchers have discovered a high-fat diet may impair important receptors located in the stomach that signal fullness. As published in the journal PLOS ONE, researchers from the University’s Centre for Nutrition and Gastrointestinal Diseases—based at SAHMRI—investigated the association between hot chili pepper receptors (TRPV1) in the stomach and the feeling of fullness, using laboratory studies.
“The stomach stretches when it is full, which activates nerves in the stomach to tell the body that it has had enough food. We found that this activation is regulated through hot chili pepper or TRPV1 receptors,” according to Amanda Page, an associate professor and senior research fellow in the University of Adelaide’s School of Medicine, as well as lead author on the paper.
“It is known from previous studies that capsaicin, found in hot chilies, reduces food intake in humans. And what we’ve discovered is that deletion of TRPV1 receptors dampens the response of gastric nerves to stretch, resulting in a delayed feeling of fullness and the consumption of more food. Therefore, part of the effect of capsaicin on food intake may be mediated via the stomach. We also found that TRPV1 receptors can be disrupted in high-fat diet-induced obesity.”