Obesity and the Digestive System
David Y. Hui, PhD
Professor
Department of Pathology and Laboratory Medicine
Description of Research
Dr. Hui investigates two areas related to lipid metabolism and diet-induced metabolic diseases. The first focuses on the role of pancreatic lipolytic enzymes in dietary lipid absorption, metabolism, and impact on metabolic diseases including obesity. The second studies the effects of apoE and its interaction with LDL receptor related proteins (LRP) in lipid transport, cell signaling, and modulation of metabolic diseases. He uses gene targeting approach to produce mice with defective expression of each of the pancreatic lipolytic enzymes (CEL, pancreatic phospholipase A2 [PLA2], and pancreatic triglyceride lipase [PTL]), and then tests their efficiency in lipid absorption and transport. Mice lacking CEL enzyme absorb lipid and cholesterol efficiently, but intestinal lipoproteins produced from the CEL-null mice are smaller than normal chylomicrons. In contrast, mice lacking PTL display reduced cholesterol absorption efficiency and delayed fat absorption and metabolism, whereas the PLA2-defective mice have normal lipid absorption and transport mechanisms but are resistant to diet-induced obesity and diabetes. Current research is being undertaken to determine the mechanism by which CEL influences chylomicron production.
Collaborations and Core Use
Dr. Hui collaborates with Drs. Aronow (in the Bioinformatics Core), Seeley, and Tso to investigate lipid metabolism. He also works with Dr. Heubi investigating the molecular mechanism of cholesterol absorption and the influence of apolipoprotein E polymorphism on diet-induced obesity and obesity-related metabolic complications. Anticipated Core Use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.
