The role of the phosphatidylserine receptor Brain-specific angiogenesis inhibitor 1 (BAI1) in diet induced obesity

• Applicant: Dr. Christian Maueröder
• Subject Area: Endocrinology, Diabetology, Metabolism ; Gastroenterology ; Immunology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 399299135

More than 2 billion people worldwide are characterized as overweight or obese. This situation brings the need for novel therapeutic strategies. Diet induced obesity is characterized by massive adipocyte cell death and tissue remodeling in the visceral fat pad. It is unclear how dead adipocytes contribute to diet induced obesity and associated metabolic complications. However, if dead adipocytes have a pathological value, boosting their removal should ameliorate the complications of diet induced obesity. Preliminary experiments in the laboratory of Prof. Ravichandran have shown that the phosphatidylserine receptor brain-specific angiogenesis inhibitor 1 (BAI1) is mediating the response to high fat diet in mice. BAI1 is involved in the clearance of apoptotic cells, but has also been implicated in other settings as well. Being expressed by both monocytes/macrophages and adipocytes, we hypothesize that BAI1 is involved in the phagocytic removal of dead adipocytes and mediates adaption of adipocytes to high fat diet. By deploying promoter-specific knockout or overexpression of BAI1, we will characterize the role of BAI1 in monocytes/macrophages and adipocytes during feeding with high fat diet.An increasing number of studies indicates that the pathology of diet induced obesity is complex. We wish to address the role of BAI1 during diet induced obesity at the intersection of immune function and metabolism. Since cell metabolism and cell function are closely linked, we intend to understand how BAI1 influences the action of monocytes/macrophages and adipocytes in response to feeding with high fat diet. With our efforts, we aim to obtain new insights into the role of adipocyte clearance, phosphatidylserine sensing, and metabolic functions of BAI1 in diet induced obesity. These results will also help to assess the therapeutic potential of interfering at the level of adipocyte clearance and BAI1 activity. If we confirm the preliminary data on BAI1 during high fat diet, we will design single-domain antibodies engaging BAI1 and test their applicability for treatment of obesity.

• DFG Programme: Research Fellowships
• International Connection: Belgium
• Host: Professor Kodi S. Ravichandran