Posted on Jul 07, 2020, 1 p.m.
Yale School of Medicine researchers suggest that they 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; findings published in the Proceedings of the National Academy of Sciences indicate that this molecule may be a promising therapeutic target to control this inflammation and to keep metabolic disease in check.
Lead author Xiaoyong Yang says that when an individual overeats the body stores the excess calories in the form of fat in adipose tissue, as the amount of calories intaken continues to increase it leads to inflammation in the adipose tissues and the release of fatty acids into other tissues, including the muscles and liver, which is dangerous and leads to metabolic disorders such as diabetes.
Overeating is known to lead to inflammation and metabolic disease, but the precise way that the body’s immune cells react to excess calorie consumption to contribute to this process was not known until now. The team focussed on the O-GlcNAc signaling pathway that is activated when an individual overeats to instruct the cells to limit inflammation.
“The body is smart,” said Yang, associate professor of comparative medicine and of cellular & molecular physiology. “It tries to protect against inflammation when fat builds up in the body. We discovered a key pathway that quenches inflammation caused by overnutrition.”
O-GIcNAc transferase enzymes that activate GIcNAc signaling were found to be responsible for activating the body’s pro-inflammatory response by turning on/off a specific signaling pathway in macrophages; finding suggests that OGT may be a target for new therapies to suppress inflammation and improve health.
“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.”
Additionally this study sheds light on the workings of glucosamine and glutamine nutritional supplements that are recommended to help treat arthritis and inflammation in the joints; it was known that these supplements promote O-GIcNAc signaling and decrease inflammation but it was not known how the process worked until now.
“Our finding further implicates how glutamine and glucosamine suppress inflammation,” Yang said.
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