Despite extensive efforts to prevent and treat obesity and type 2 diabetes, the prevalence has reached pandemic proportions worldwide. Therefore, the scientific efforts to understand the physiological and molecular mechanisms that control body weight and insulin resistance must be intensified for identifying novel and better therapeutic target sites.
Our group focuses on endocrine and molecular mechanisms that enhance energy expenditure to improve body weight and metabolic health. Fibroblast growth factor 21 (FGF21), a circulating protein, is a very promising target. Exogenous FGF21 administration improves adiposity and serum lipid levels in mice and humans. However, little is known of FGF21’s endogenous role. Notably, the knowledge on the molecular action is absolutely required for the development and design of safe efficient anti-obesity drugs. A main target of FGF21 action is the activation of thermogenic adipose tissue. In contrast to white adipose tissue (WAT), which is the main tissue for energy storage, brown adipose tissue (BAT) dissipates energy as heat. Exploring how WAT can be converted into a brown fat-like phenotype (“browning”, beige/brite fat) may improve the therapy of obesity. Thus, we are investigating the physiological significance, the underlying molecular mechanisms and whether the thermogenic mitochondrial uncoupling protein 1 is required for the beneficial effects of browning.
To address our specific research aims, we make use of loss- and gain-of-function models in vitro and in vivo, combined with mouse metabolic phenotyping and in depth molecular characterization including cellular bioenergetics.
Keywords:
Metabolic syndrome, energy metabolism, endocrine cross-talk, thermogenesis, adipose tissue, mouse metabolic phenotyping, mitochondria
Selected publications)
1) Keipert S., Lutter D., Schroeder B.O., Brandt D., Ståhlman M., Schwarzmayr T.,
Graf E., Fuchs H., Hrabe de Angelis M., Tschöp M.H., Rozman J., Jastroch M. (2020) Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice Nature Communications, Volume 11, (624)
2) Keipert S., Kutschke M., Ost M., Schwarzmayr T., van Schothorst E.M., Lamp D., Brachthäuser L., Hamp I., Mazibuko S.E., Hartwig S., Lehr S., Graf E., Plettenburg O., Neff F., Tschöp M.H., Jastroch M. (2017) “Long-Term Cold Adaptation Does Not Require FGF21 or UCP1.” Cell Metabolism, 26(2):437-446
3) Keipert S., Kutschke M., Lamp D., Brachthäuser L., Neff F., Meyer CW., Oelkrug R., Kharitonenkov A., Jastroch M. (2015) “Genetic disruption of uncoupling protein 1 (UCP1) in mice renders brown adipose tissue a significant source of FGF21 secretion”; Mol Metab. 4(7): 537–542
4) Keipert S.*, Ost M.*, Johann K. Imber F., Jastroch M., van Schothorst EM, Keijer J., and Klaus S. (2014) “Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine”; Am J Physiol Endocrinol Metab 306: E469–E482
5) Keipert S., Jastroch M. (2014) “Brite/beige fat and UCP1 — is it thermogenesis?”; Biochimica et Biophysica Acta 1837; 1075–1082
