A naturally occurring hormone that stimulates thermogenesis—the burning of calories to create heat—is most abundant during exercise or exposure to cold. But the hormone, called meteorin-like protein or Metrnl, may not be just for exercise anymore. It is produced in the laboratory. Also, Metrnl, when injected, appears to provide some of the same benefits as exercise. In a study with mice, Metrnl injections not only burned fat, it improved blood sugar control and activated anti-inflammatory genes. Finally, Metrnl increased fat-burning in mice that were exposed to cold temperatures, helping the mice maintain core heat production.

Metrnl’s health-promoting properties make it a promising candidate for treating obesity and other metabolic diseases, inflammation, and possibly other disorders.

In the study with mice, researchers at Dana-Farber Cancer Institute found that Metrnl injections decreased body fat by 25% and caused weight losses even in mice that were on a high-fat diet. Additional details from the study appeared in a paper published June 5 in Cell, in an article entitled “Meteorin-like Is a Hormone that Regulates Immune-Adipose Interactions to Increase Beige Fat Thermogenesis.”

The researchers, led by Bruce Spiegelman, Ph.D., discovered that unlike other exercise-related proteins that burn fat, Metrnl works mainly through the immune system, rather than directly on fat cells. Metrnl activates an alternative molecular pathway by which immune cells are recruited to enter fatty tissue, where they trigger the fat-burning process.

“The idea of a protein acting primarily through the immune cells in the fat is pretty amazing, at least in our view,” Dr. Spiegelman said.

The Metrnl findings come two years after the Spiegelman group isolated a different protein, irisin, produced in muscles by endurance as opposed to resistance exercise, which stimulates Metrnl secretion. Irisin also promotes the browning of fat to release energy and causes mice to lose weight; like Metrnl, irisin improves glucose tolerance, which helps prevent diabetes.

The Spiegelman group had identified irisin in a search for genes and proteins regulated by a master metabolic regulator, called PGC1-alpha, that is turned on by exercise. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, the Spiegelman group established that Metrnl promotes browning by inducing cytokines IL4/IL13 and M2 macrophage activation.

“Metrnl stimulates an eosinophil-dependent increase in IL-4 expression and promotes alternative activation of adipose tissue macrophages,” the authors of the Cell paper wrote, “which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat.”

“Importantly, blocking Metrnl actions in vivo significantly attenuates chronic cold-exposure-induced alternative macrophage activation and thermogenic gene responses,” the authors continued. “Thus, Metrnl links host-adaptive responses to the regulation of energy homeostasis and tissue inflammation and has therapeutic potential for metabolic and inflammatory diseases.”

“Because it targets the immune cells involved in tissue repair it will also be interesting to see if this protein affects muscle repair in certain neuromuscular diseases,” Dr. Spiegelman added.

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