Mission Our research focuses on understanding the molecular, cellular, and systemic basis of obesity and it complications. By understanding these mechanisms and pathways our goal is to develop therapeutic strategies to ameliorate obesity and its complications.
Objectives 1. Trafficking and storage of lipid within adipocytes and liver have been implicated in the pathophysiology of obesity and its complications. One objective of our team is to investigate the proteins and pathways within these different cell types and their role in normal physiology and pathophysiology. For our studies, we utilize conditional knockout lines of mice in which expression of specific genes such as perilipin family of proteins and acyl CoA synthetase 4 and 5 can be ablated tissue specifically. Also for our studies the mice are fed differing dietary regimens that induce obesity and metabolic dysfunction. Investigation of mice on these varying dietary regimens includes non-invasive measures of body composition, indirect calorimetry, and various tests that investigate glucose/insulin homeostasis. Additionally, we utilize cell biology, confocal imaging, lipidomic, metabolomic, gene expression techniques such as RNA seq, and analysis of signaling pathways to delineate underlying pathways and mechanisms. Another research avenue is to investigate the role of adipocytes and associated metabolic pathways in metabolic dysfunction in humans.
2. A second objective focuses on the proteins and pathways by which ingested fat and fructose are absorbed within the intestine, regulate intestinal inflammation, and interact with intestinal microbiota and systemic metabolism to modulate the risk of becoming obese and developing metabolic complications. For these studies, we are utilizing several lines of conditional knockout mice as described in objective 1 as well as mice that vary in their genetic background. In addition to the techniques described in objective 1 we also perform analysis of intestinal microbiota composition and metabolism and varying techniques to elucidate role of microbiome in modulating systemic physiology,
3. A third objective is to determine the underlying mechanisms that promote adipose tissue and liver inflammation in response to various to high caloric feeding and fructose. In these studies we will investigate the role of various target genes and pathways. For example we are also investigating the role of ACSL4 in immune cells and other tissues in obesity associated adipose tissue inflammation and atherosclerosis.
Lab Members Andrew S. Greenberg, M.D.
Lead Scientist, Senior Scientist
Research focus: Etiology of obesity and its complications; the role of inflammation in metabolic disorders and the regulation of adipocyte metabolism, inulin resistance, and diabetes