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ADIPOSE TISSUE INFLAMMATION

Martin Gericke


Adipose tissue inflammation is closely linked to the onset of type 2 diabetes and other obesity-associated diseases. Using live-imaging technology, our group studies the interaction of macrophages and adipocytes as well as with other immune cells to unravel inflammatory and non-inflammatory functions of adipose tissue macrophages in obesity. Our aim is to find new pharmacological targets to influence adipose tissue inflammation and treat type 2 diabetes.


Data

Email : martin.gericke@medizin.uni-leipzig.de

Phone : +49 341 9722073

Address : Institute of Anatomy | Eilenburger Str. 13-15 | D-04317 Leipzig


Project_1

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.

Figure 1: Two time-lapse movies unravel fundamentally different clearing behaviour of macrophages in adipose tissue (AT). AT explants showing macrophages (red) and adipocytes (green). Upper row: One macrophage detects, internalizes and digests a small adipocyte remnant (star), a process leading to efficient removal of the adipocyte remnant within ~36 h. Lower row: After initial contact between macrophages and a hypertrophic adipocyte (star), more macrophages become attracted, resulting in a CLS formation with now signs of efficient degradation after 4 days. Scale bar represents 50 µm.


Project_2

Role of innate immune system on obesity-related inflammation in adipose tissue

Nora Klöting (IFB Adiposity diseases, Leipzig) and Martin Gericke (Institute of Anatomy, Leipzig)

Funded by IFB Adiposity diseases

The causal link between obesity and inflammation is well established. While the exact reasons for this chronic immune response to obesity are unclear, there is strong evidence to suggest that innate inflammatory systems link obesity and associated diseases. Inbred mice strains are strikingly different in susceptibility to diet induced obesity (DIO), demonstrating a role genetic factors in the development of DIO.

To address the role of innate immune system, inflammation and obesity, we established a new congenic mouse, with an exchanged major histocompatibility complex (MHC, H2 region) region between obesity-resistant 129S6/SvEvTac and obesity-prone C57BL/6 mice. The new constructed congenic line, BL6.MHC129, will give the possibility to analyze the role of innate immune system on obesity-induced inflammation in adipose tissue and obesity related traits.