MIF Identified as Key Driver of Irreversible Fat Loss in Cancer Cachexia

A Closer Look at the Role of MIF

a cytokine called macrophage migration inhibitory factor (MIF).

MIF, secreted by tumors, triggers chronic inflammation in fat tissue while suppressing the ability of stem cells to become mature fat cells. This process leads to significant fat depletion, contributing to the progression of cachexia.

Cancer cachexia is a complex condition that accounts for 20% of all cancer-related deaths. It leads to severe weight loss, muscle dystrophy, loss of appetite, and decline in physical function. Despite its prevalence, the mechanisms underlying its development have remained poorly understood.

Traditionally, cancer cachexia has been considered a metabolic syndrome induced by tumors, with nutritional support being the primary intervention. However, clinical observations have shown that even with adequate nutrition, patients are unable to regain weight.

This research sheds new light on the role of MIF in cachexia. The team, led by Xiao Ruiping and Hu Xinli, discovered that MIF triggers chronic inflammation and fibrosis in fat tissue through interaction with its receptor ACKR3. This impairs the ability of stem cells to develop into functional fat cells, even if there are enough nutrients.

Further research revealed a strong correlation between elevated MIF levels in the blood and the degree of weight loss in patients with lung, stomach, or colorectal cancers. In mouse models of cancer cachexia, inhibiting MIF-ACKRs using genetic or pharmacological approaches effectively alleviated fat loss and other clinical manifestations of cachexia.

"For cachexia patients, it is difficult to store energy in their fat tissue. The problem is not a lack of nutrition, but rather a disruption in how nutrients are normally distributed in the body," Hu said. "MIF is a key factor that leads to the irreversible damage of fat tissue," she added.

This research suggests that targeting MIF could be a promising therapeutic approach for cancer cachexia. The research team is now working on the development of inhibitors of MIF-ACKR3, hoping to create effective drugs to treat cancer cachexia and improve the quality of life for patients.