Effects of obesity and anti-obesity treatments on pancreatic cancer
Adipose tissue, formerly considered as passive storage organ for triglycerides is now recognized as a highly active endocrine organ. Dysfunctional adipose tissue in obesity releases an altered profile of adipokines and cytokines (adipocytokines), which have been linked to obesity related co-morbidities such as type 2 diabetes, cardiovascular disease and cancer, including PDAC. Next to the adipocytokines, adipose tissue derived extracellular vesicles (EVs) emerged as novel signaling moiety in mediating inter-organ communication. However, the effect of adipose tissue-derived EVs on the pancreas and on PDAC development remains to be determined.
Our central question is built upon the hypothesis that in a state of obesity, dysfunctional adipose tissue contributes to a tumor promoting macro-environment and facilitates the progression of pre-neoplastic lesions. Improvements of adipose tissue function after therapeutic weight loss such as diet, pharmaceutical and surgical weight loss strategies may modify that risk.
By combining mouse models of obesity, weight loss and PDAC development, we aim to study the specific impact of body adiposity and adipose tissue remodeling on PDAC development. Ultimately, results of this study will guide us in our long-term quest to develop novel PDAC prevention and treatment strategies that are tailored towards obese patients.
Stemmer, K., Finan, B., DiMarchi, R. D., Tschop, M. H., and Muller, T. D. (2020). Adv Drug Deliv Rev
Jall, S., De Angelis, M., Lundsgaard, A. M., Fritzen, A. M., Nicolaisen, T. S., Klein, A. B., Novikoff, A., Sachs, S., Richter, E. A., Kiens, B., Schramm, K. W., Tschop, M. H., Stemmer, K., Clemmensen, C., Muller, T. D., and Kleinert, M. (2020). Diabetologia 63, 1236-1247
Stemmer, K., Muller, T. D., DiMarchi, R. D., Pfluger, P. T., and Tschop, M. H. (2019). J Clin Invest 130, 4058-4071
Brandt, S. J., Muller, T. D., DiMarchi, R. D., Tschop, M. H., and Stemmer, K. (2018). J Intern Med 284, 581-602