B4: Role of severe obesity in healing of muscle injuries

PIs: U. Knippschild, M. Wabitsch

In obesity, adipose tissue functions are dysregulated leading to changes in the release of growth factors, adipocytokines, cytokines, chemokines, hormones, and fatty acids, which are secreted from adipocytes and macrophages resident in white adipose tissue. These changes affect lipid metabolism, glucose homoeostasis, inflammation, angiogenesis, haemostasis, and blood pressure. In addition, the ectopic lipid accumulation in organs and tissues can lead to severe co-morbidities including heart disease, diabetes, metabolic syndrome, hypertension, sleep apnea, and cancer. Furthermore, there is increasing evidence that obesity impairs tissue regeneration processes after trauma. For example, obesity negatively affects regeneration of skeletal muscle injuries, yet the underlying mechanisms have not been elucidated. Muscle regeneration can be divided into an initial response, i.e. the peak inflammation and degenerative response, and the structural and functional recovery phase. It is a highly synchronised process demanding the timely coordinated activation of different cellular responses by many different signalling molecules. There is evidence that toxic lipid metabolites and pro-inflammatory adipocytokines and chemokines as well as leptin and insulin resistance impair these processes, especially muscle satellite activation and functions, finally resulting in decreased regenerative ability. The aim of our project is to investigate (i) the role of lipid metabolites and fatty acids on muscle regeneration, (ii) the consequences of an altered interplay between macrophages and stem cells on muscle regeneration, and (iii) how changes in signal transduction pathways affect satellite cell physiology. The results of our project will lead to the identification of new obesity-related fac­tors with prognostic and therapeutic relevance in regard to muscle regeneration after injury.

Video

Projektleiter

Prof. Dr. Uwe Knippschild
Universitätsklinikum Ulm
Zentrum für Chirurgie
Klinik für Allgemein- und Viszeralchirurgie
Albert-Einstein-Allee 23
89081 Ulm
Tel.: +49 731 500 53580
Fax: +49 731 500 53582
uwe.knippschild(at)uniklinik-ulm.de

 

Prof. Dr. Martin Wabitsch
Universitätsklinikum Ulm
Klinik für Kinder- und Jugendmedizin 
Sektion Pädiatrische Endokrinologie u. Diabetologie 
Interdisziplinäre Adipositasambulanz 
Eythstr. 24
89075 Ulm
Tel.: +49 731 500 57401
Fax: +49 731 500 57407
martin.wabitsch(at)uniklinik-ulm.de

Influence of obesity on inflammatory responses and cross talk of immune cells (mod. from Pillon et al. 2013)
Interactions between immune cells and muscle cells after injury are influenced by obesity released factors and obesity related metabolic dysfunction