Results from the study conducted by researchers from the Harvard T.H. Chan School of Public Health showed a connection between inflammation and dysfunction in the endoplasmic reticulum (ER), a mini-organ inside cells that plays a key role in the synthesis of many proteins and lipids. ER dysfunction is involved in the development of type 2 diabetes. The study results suggest that treatments targeting this connection could be beneficial for metabolic disease.
The function of the ER is essential for the liver and other organs to preserve adequate levels of glucose in the body. In the study the team of researchers examined liver cells to show that obesity-associated inflammation can increase the production of nitric oxide (NO), a powerful gas that can cripple the ER.
According to Gokhan S. Hotamisligil, senior author of the study these results indicate that in the presence of chronic inflammation, mini organs like the ER lose their energy through a specific link, and treatments targeting inflammatory pathways, including nitric oxide production, could be effective treatments for metabolic disease.
In patients with obesity, the ER is incapable of initiating intracellular processes known as the unfolded protein response (UPR), responsible for relieving the ER stress and restoring function. Results from this new research suggest that the sequence might be the reverse. According to the study results it is obesity-related inflammation that impairs the UPR response and thus ER function.
Using a new strategy, the team engineered a form of IRE1 that could not be modified by NO, and found that it protected against the negative effects of inflammation and improved metabolic control in mice with obesity.