Elucidating the mechanism of hepatic selective insulin resistance.

Annually at least 2.8 million adults die as a consequence of obesity-associated disease.  In Belgium, about 50% of the population has overweight or obesity, and 1 in 12 adults has diabetes of which 80% is attributable to overweight (www.diabetes.be). Thus, there is an urgent need for increased understanding of pathogenesis due to obesity and more effective treatments.  In response to sustained positive energy balance, fat cells store excess energy as lipids, leading to obesity. Obesity is associated with insensitivity to the glucose-lowering hormone insulin, ultimately causing chronically high levels of blood glucose. High blood glucose level is a unifying feature of obesity-associated metabolic diseases including diabetes and fatty liver disease.  However, it is unclear how obesity causes insulin insensitivity and thereby high blood glucose level, at the molecular level.  We will tackle this basic and clinically important question by elucidating molecular changes in fat tissues by studying model organisms such as mice and naturally diabetic Mexican cavefish but also fat biopsies from patients with obesity and diabetes.  Our research will hopefully provide novel therapeutic strategies for obesity-associated metabolic diseases.