![Inflammation From Obesity Could Be Beneficial, Not Detrimental Inflammation From Obesity Could Be Beneficial, Not Detrimental](https://images.medindia.net/health-images/1200_1000/obesity-3.jpg)
“This finding is completely contrary to the general dogma in the diabetes field that low-grade inflammation in obesity causes insulin resistance and type 2 diabetes,” notes Umut Ozcan, MD, Endocrinology Division of the hospital. He had led the research.
His team previously showed that obesity places stress on the endoplasmic reticulum (ER), a structure in the cell where proteins are assembled, folded and dispatched to do jobs for the cell. This so-called “ER stress” impairs the body’s response to insulin in maintaining appropriate blood glucose levels, and is a key link between obesity and type 2 diabetes. Last year, Ozcan and colleagues showed that a protein that relieves ER stress, called XBP1s, cannot function in obese mice. Earlier this year, they showed that activating XBP1s artificially in the liver normalized high blood sugar in obese, insulin-resistant type 2 diabetic mice (as well as lean, insulin-deficient type 1 diabetic mice).
The new study shows that a second protein triggered by inflammatory signals, p38 MAPK, chemically alters XBP1s, enhancing its activity — and that without these alterations, XBP1s cannot function to maintain normal glucose levels. The study further showed that obese mice have reduced p38 MAPK activity, and that re-activating p38 MAPK in the liver reduced their ER stress, increased insulin sensitivity and glucose tolerance, and significantly reduced blood glucose levels.
Together, the findings suggest that either increasing p38 MAPK activity — despite its being an inflammatory signal — or increasing XBP-1 activity by other means could represent new therapeutic options for diabetes.
The study also suggests a new model for understanding type 2 diabetes, in which obesity may interfere with the ability of people’s cells to respond to inflammatory signals. “It may be that inflammatory pathways are not working optimally and there could be a resistance to cytokines which mediates the inflammation,” Ozcan says. “This could be a paradigm shift for the field.”
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