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Researchers at Yale have identified a molecule that plays a key role in the body's inflammatory response to overeating, which can lead to obesity, diabetes, and other metabolic diseases.

When a person overeats, the body stores excess calories in the form of fat in the adipose tissue, or body fat

 As the amount of calories consumed continues to increase, this leads to inflammation in adipose tissue and the release of fatty acids into other tissues, including the liver and muscles..

Researchers were aware that overeating led to inflammation and metabolic diseases, but until now, they did not know the precise way that the body's immune cells, such as macrophages—which react to excess calorie consumption—contributed to this process. The new research by Yang and team zeroed in on a pathway called O-GIcNAc signaling, which activates when a person overeats, instructing the cells to limit inflammation.

In particular, the researchers found that OGT (O-GIcNAc transferase), an enzyme that activates GIcNAc signaling, was responsible for activating the body's pro-inflammatory response by turning on or off a specific signaling pathway in macrophages.

"The macrophage can be a good guy or a bad guy," Yang said. "It becomes a bad guy in overnutrition, secreting a lot of inflammatory factors. In other contexts, it's a good guy and has an anti-inflammatory effect. We found out that OGT tries to stop the macrophage from becoming a bad guy—to stop the pro-inflammatory response."

 

Yunfan Yang et al. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.1916121117