Project Number: 8050-51000-097-02-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: May 1, 2014
End Date: Apr 30, 2019
LAB NAME: Obesity and Metabolism 1: Determine the mechanistic roles of the intestinal and hepatic proteins ACSL5 and plin2 in fatty acid metabolism, especially in delivery of dietary triacylglycerol to tissues and tissue lipogenic metabolism. 1A) To determine the role of intestinal enterocyte ACSL5 expression in regulating fatty acid trafficking, TG formation, and metabolism, fat oxidation, gene expression, enteroendocrine hormone secretion, and chylomicron secretion. 1B) To determine the role of intestinal enterocyte plin2 expression in regulating fatty acid trafficking, TG formation, and metabolism, fat oxidation, gene expression, enteroendocrine hormone secretion, and chylomicron secretion. 1C) To determine the role of ACSL5 expression in regulating hepatocyte fatty acid and TG metabolism, hepatic steatosis, and hepatic insulin sensitivity. 1D) To determine the role of plin2 expression in regulating hepatocyte fatty acid and TG metabolism, hepatic steatosis, and hepatic insulin sensitivity. 2: Determine the physiologic actions and consequences of ACSL5 in diet-induced obesity and obesity associated metabolic complications. 2A) To determine the mechanisms and relative role of ACSL5 expression in the intestine on diet-induced obesity and its metabolic complications.
LAB NAME: Obesity and Metabolism To address the role of acyl CoA synthetase 5 (ACSL5) and perilipin 2 (plin2) in intestinal enterocytes and hepatocytes we have generated conditional lines of knockout of ACSL5 and plin2 mice allowing us to disrupt in a tissue specific manner. We will investigate the physiological effects of ablation of ACSL5 and plin2 in mouse hepatocytes and enterocytes and the response to a high caloric diet in vivo. In these animal studies we will determine body composition, energy expenditure, insulin glucose homeostasis, fat absorption, hepatic steatosis, and in liver and intestine tissues gene expression will be determine. In isolated hepatocytes studies in our mice we will triglyceride (TG) accumulation, and TG oxidation. The studies in this project will provide novel insights that will allow researchers to direct therapeutic strategies to protect against the development of obesity and associated complications.