Grant: Operating Grant

The rise in type 2 diabetes is alarming. Insulin resistance precedes diabetes, can last for decades and is reversible. This provides a chance to prevent the onset of diabetes. Over half of Canadians are overweight, which is the most significant factor contributing to insulin resistance. Obesity is associated with a chronic inflammation, which is critical in causing insulin resistance. The trigger for this inflammation is not clear. We have discovered that a part of bacterial cell wall (i.e. peptidoglycan) links inflammation and insulin resistance during obesity. Different types of this bacterial cell wall are detected by two separate immune proteins. We discovered that one of these bacterial sensors (i.e. NOD1) causes inflammation and insulin resistance during obesity, but the other (i.e. NOD2) is actually protective. These bacterial sensors regulate the type of bacteria in our gut and how some of these bacteria can get into the surrounding fat tissue. This is a potential trigger for inflammation during obesity. It is not yet understood why only certain obese individuals develop insulin resistance. This work can enhance the identification of people that are susceptible to diabetes by finding and linking bacterial and inflammatory markers of disease. Understanding the difference obesity-induced inflammation mediated by NOD1 and NOD2 provides a new way to probe bacterial and inflammatory causes of insulin resistance. The objective of this research is to understand how NOD1 causes, but NOD2 protects against insulin resistance. This research will help direct novel nutritional interventions including specific prebiotics and probiotics and may identify new therapies that could prevent type 2 diabetes. This research is also relevant to patients with specific gut inflammatory pathologies. This work may direct changes in the monitoring or care of obese patients with gut diseases and/or diabetes.