Key signal for activating beige fat holds promise for obesity prevention

University of Illinois Chicago scientists have identified a cellular pathway that changes the most common type of fat, which stores energy, into a less common type, which burns energy. The finding could be significant for preventing obesity and metabolic diseases such as diabetes, the authors said. 

Fat cells come in different colors: white, brown and beige. White fat cells, the dominant type in the body, store energy and drive weight gain. Brown fat helps maintain body temperature by burning calories to generate heat in low temperatures. While these types of fat are always present in the body, beige fat — which burns calories like brown fat does — only appears during cold exposure.

Identifying the cellular switch that creates beige fat and turning it on at normal temperatures could help prevent diet-related weight gain and associated health risks. In a new paper in Science Advances, UIC scientists, led by Yuwei Jiang of the UIC College of Medicine, report finding this switch in the local lymph nodes embedded in white fat, where an immune-system factor triggers the activation of beige fat cells.

Experiments identified a small protein called CCL22 as essential to the production of beige fat during cold exposure. Removing local lymph nodes or blocking this immune factor prevents beige cells from forming; adding it back restores the process. When mice on a high-fat diet were given injections of the protein, it increased this transformation and prevented obesity.

The researchers also looked at blood samples from humans in an intermittent-fasting study led by UIC’s Krista Varady. They found lower levels of the CCL22 protein in obese people before fasting, and that the diet increased CCL22 levels in those who lost weight during the study.

More studies are needed to show that the protein stimulates weight loss and doesn’t just prevent weight gain, Jiang said. The immune factor also has been linked to cancer-promoting effects, suggesting that other parts of the cellular pathway may be better targets for future interventions. But the preliminary evidence is promising for both obesity and aging, she said.  

“Obesity causes a loss of beige fat, and aging causes the same problem,” said Jiang, an assistant professor in the department of physiology and biophysics. “So we may be able to use this same pathway to recover beige fat activation in older individuals and reestablish energy balance, potentially preventing obesity and associated health disorders such as Type 2 diabetes, heart disease and chronic inflammation.” 

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