Grant: Project Grant

Obesity, a consequence of multifaceted interactions between dietary and genetic factors, is reaching epidemic proportions in Western countries. Prevention/reduction of weight gain is an effective strategy against the development of metabolic diseases (such as diabetes and atherosclerosis). We have developed a novel mouse model that has reduced production of a specific fat (phosphatidylcholine) in the intestine; this was accomplished by selectively deleting a key enzyme, CTa, required for phosphatidylcholine synthesis. When intestinal-specific CT knockout (iCTa-/-) mice are fed a high fat diet they gain less weight versus control mice. Furthermore, iCTa-/- mice have lower levels of circulating lipids and glucose following a meal. We now wish to understand the link between intestinal PC synthesis, dietary fat consumption and weight gain, with the hope to develop new therapies for the treatment and prevention of metabolic diseases.