Study: Why we lose fat and muscle during infection?

A new study by Salk scientists has found that the wasting response to infection is not a single process, but two distinct phases regulated by different immune cells. While fat loss did not benefit the fight against infection, muscle loss did—a surprising clue that some wasting may help manage illness.

The findings, published in Cell Reports on July 24, 2023, can inform the development of more effective therapeutics that spare people from wasting and increase our understanding of how wasting influences survival and morbidity across infections, cancers, chronic illnesses, and more.

"We often make assumptions that conditions like wasting are bad, since they often coincide with higher mortality rates," says senior author Janelle Ayres, Salk Institute Legacy Chair and head of the Molecular and Systems Physiology Laboratory. "But if instead we ask, what is the purpose of wasting? We can find surprising and insightful answers that can help us understand the human response to infection and how we can optimize that response."

Defending the body from an invader requires a lot of energy. Prior studies suggested this immune-related energy consumption had the unfortunate consequence of wasting. But Ayres and team were curious to know whether wasting could be beneficial and not just a side effect.

The researchers found that CD4+ T cells acted first and initiated the process of fat wasting. Afterward, but completely independently of the fat wasting, CD8+ T cells initiated the process of muscle wasting. The CD4+ T cell-induced fat wasting had no impact on the ability for the mice to fight T. brucei or to survive infection. The CD8+ T cell-induced muscle wasting, however, contrary to the traditional assumptions about wasting, helped the mice fight T. brucei and survive the infection.

The findings illustrate the important role of immune cells in both fat and muscle wasting and the necessity to understand the function of such responses to inform therapeutic interventions.

"We can learn so much about our immune systems by looking at the environments and infections we have co-evolved with," says Ayres. "While T. brucei is an interesting and important case, what is exciting is extrapolating our findings to understand, treat, and overcome any disease that involves immune-mediated wasting—parasites, tumors, chronic illnesses, and so much more."

In the future, the team will examine the T cell mechanism in other mammals and eventually humans. They also want to explore in more detail why muscle wasting is occurring and why CD4+ and CD8+ T cells play these distinct roles.

Journal Information: Janelle S. Ayres, CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection, Cell Reports (2023). DOI: 10.1016/j.celrep.2023.112814. www.cell.com/cell-reports/full … 2211-1247(23)00825-2