Grant: Master's Award: Canada Graduate Scholarships

Obesity is a major risk factor for the development of metabolic complications such as insulin resistance and type 2 diabetes. However, some obese individuals do not develop insulin resistance and it seems that certain characteristics of adipose tissue (fat) such as inflammation and fibrosis could differentiate insulin-resistant obese from a subpopulation of obese individuals who remain sensitive to this hormone. Several studies report an increased presence of inflammation and fibrosis in adipose tissue of obese patients compared with normal-weight subjects. A recent publication also suggests that insulin-resistant obese individuals have a reduced activity of the energy-sensing enzyme AMP-activated protein kinase (AMPK) in their adipose tissue when compared with insulin-sensitive obese individuals and that this is associated with increased inflammation in these patients. We are interested in how the activity of this enzyme is related to adipose tissue inflammation and fibrosis and to whole-body insulin resistance in obese humans. By comparing the characteristics of adipose tissue of different phenotypes of obese individuals (insulin-sensitive, insulin-resistant, type 2 diabetics) to metabolically healthy, normal-weight individuals, we will delineate factors that can either prevent or contribute to the development of insulin resistance, regardless of obesity. Finally, we are interested in how the relationship between AMPK, inflammation, fibrosis and insulin resistance is affected by weight loss. To test this, insulin-sensitive, insulin-resistant and type 2 diabetics obese patients will undergo bariatric surgery. We will then analyze samples of their adipose tissue and assess their sensitivity to insulin 6 months after the surgery. This project aims at increasing the knowledge regarding the mechanisms that lead to metabolic complications of obesity in humans and could therefore raise new options for earlier detection and for the development of more specific treatments.