Comparative biology and biomedicine of brown adipose tissue

Project leader: Dr. Martin Jastroch

Our research focuses on the biology of thermogenic adipose tissue, and is best known for deciphering the evolution of adipose thermogenesis using comparative aspects. We aim to apply this knowledge to develop technologies activating metabolism in human adipose tissue to combat metabolic diseases. 

In previous studies, we have fused ecological, physiological, cellular, biochemical and molecular data to discover and characterize the evolutionary origin of mammalian thermogenesis and brown adipose tissue. We disproved the tenet claiming that uncoupling protein 1 (UCP1) is restricted to mammals (Jastroch et al. 2005, Physiol Genomics). We identified UCP1 in marsupials and delineated controversial research on the presence of brown fat in marspials (Jastroch et al. 2008). We identified functional brown fat in proto-endothermic eutherian species, suggesting a role in parental care and thus, the evolution of mammalian endothermy (Oelkrug et al. 2013, Nature Commun). We comprehensively analyzed the disappearance of the UCP1 gene in mammalian evolution (Gaudry et al. 2017, Science Adv). Next, we aim to understand the molecular networks that wire thermogenesis into adipocytes using systems biology and "omics" approaches. 

Uncoupling proteins 

Project leaders: Mr Michael Gaudry (MSc), Mr Erik Rollwitz (MSc)

We focus on uncoupling proteins/UCPs and their physiological function, as they may control the adjustments and adaptation of mitochondrial bioenergetics in response to physiological challenge and metabolic stress. We apply the evolutionary approach by comparing structure-function relationships of diverse mammalian UCPs to understand molecular mechanisms and adaptation to environment and physiology (Project lead: Gaudry).  We generated knockout models to understand the ancient function of UCPs in the vertebrate kingdom, in particular in ectothermic vertebrates (Project lead: Rollwitz). Specifically, we aim to delineate the original function of UCP1 before executing mammalian thermogenesis, and the enigmatic function of UCP2 and UCP3 per se.

Human adipocyte bioenergetics and thermogenesis

Project leader: Dr. Michaela Keuper 

We use our discoveries of thermogenic networks in animal models to engineer thermogenesis into human adipocytes. With the aim to improve fat burning capacities and metabolic turnover in human fat, we hope to form the biomedical basis to combat metabolic diseases such as diabetes and obesity. In our current work, we explore the ability of human adipocytes to combust energy through alternative, UCP1-independent thermogenesis.

Mouse metabolic phenotyping

Project leader: Ms Maria Kutschke 

We consolidate the physiological importance of our molecular findings by comprehensive mouse metabolic phenotyping. Recently, we have shown that major metabolic regulators, such as the hormone FGF21 and UCP1 of brown fat, are dispensable for long-term maintenance of metabolism and body temperature in the cold, opening opportunities to study alternative routes of thermogenesis (Keipert et al. 2017, Cell Metabolism). To achieve this, we have created new mouse models to address the importance of UCP-independent thermogenesis and metabolism.

Collaborations on cellular bioenergetics

We provide our expertise in cellular and mitochondrial bioenergetics to several collaboration partners around the world to address questions on cancer biology, immunology, diabetes and drug development (Divakaruni et al. 2014, Methods in Enzymology; for further details pubmed query : Jastroch M).

Key technologies

  • Measurement of modular kinetics in isolated mitochondria by simultaneous   polarographic, potentiometric and fluorescent measurements;
  • Measurement of oxygen consumption (mitochondrial activity) and extracellular acidification (glycolysis) using the extracellular flux analyzer (Seahorse Bioscience);
  • Measurement of plasma and mitochondrial membrane potential in intact cells (using time-lapse fluorescence microscopy and platereader-based kinetic measurements);
  • Measurement of mitochondrial reactive oxygen species in isolated mitochondria (using hydrogenperoxide sensitive probes) and intact cells (using superoxide sensitive probes).
  • Mouse metabolic phenotyping