Role of macrophages in adipocyte degradation - a live-imaging approach
Martin Gericke and ngo Bechmann (Institute of Anatomy, Leipzig)
funded by DFG-SFB 1052 "Obesity Mechanism"
Innate immune cells, such as macrophages, degrade dying cells or cell debris, a process called efferocytosis. Efficient efferocytosis licenses anti-inflammatory removal of aged or damaged cells and is crucial to maintain tissues homeostasis. In adipose tissue (AT), clearing of dead adipocytes seems to be challenging, because hypertrophic adipocytes in obesity can exceed more than 150 µm in diameter, a dimension about 10-fold bigger than regular phagocytes. To investigate the molecular and cellular events following adipocyte death, we have recently established a live-imaging approach allowing us to study adipocyte - macrophage interaction after adipocyte death in living tissue. Hence, we are aiming at determining mechanisms for efficient and inefficient efferocytosis of adipocytes using our live-imaging approach combined with subsequent post-hoc super-resolution microscopy or electron microscopy. The combination of these techniques can further determine the molecular interaction between macrophages and dying adipocytes in an unprecedented spatio-temporal resolution.
This project is designed to i) unravel the molecular decision process in macrophages leading to recognition and engulfment of adipocyte remnants and, ii) study if a critical size is a natural limit for efficient, non-inflammatory removal of large particles, such as hypertrophic adipocytes in obesity. Our working hypothesis is that inefficient efferocytosis of hypertrophic adipocytes leads to a pro-inflammatory microenvironment and type 2 diabetes. Therefore, increasing scavenger function of macrophages could be a new pharmacological target to treat metabolic disease.