Comparative biology and

biomedicine of brown adipose tissue

Reconstructing the functional evolution of thermogenic UCP1

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); delineated controversial research on the presence of brown fat in marspials by identifying marsupial UCP1 (Jastroch et al. 2008); discovered functional brown fat in proto-endothermic eutherian species, suggesting an important role for eutherian evolution (Oelkrug et al. 2013, Nature Commun); and were involved in projects to demonstrate the disappearance of the UCP1 gene during 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.

Prof. Martin Jastroch

Uncoupling proteins

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. Specifically, we aim to delineate the original function of UCP1 before executing mammalian thermogenesis

A UCP1 structure-function relationships

We apply the comparative analyses to identify UCP1 structure-function relationships to understand the molecular mechanisms and ecophysiological adaptation

Dr. Michael Gaudry

B Uncoupling proteins in ectothermic vertebrates

We generated knockout models to understand the ancient function of UCPs in the vertebrate kingdom, in particular in ectothermic vertebrates

Dr. Clarissa Barthem, Erik Rollwitz

Human adipocyte bioenergetics and thermogenesis

Obesity-associated chronic low-grade inflammation impacts energy metabolism in white adipose tissue (WAT), contributing to the progression of metabolic diseases. The underlying mechanisms are not fully understood but the inflammation-metabolism axis would offer adequate therapeutic targets to treat human obesity and metabolic diseases.

A. We aim to identify the molecular nature of inflammatory pathways that modulate mitochondrial and glycolytic activity in human white adipocytes, and investigating how these pathways interact with the major signaling pathways of energy storage and dissipation to understand their impact on systemic metabolism.

B. We use our discoveries of thermogenic networks in animal models to engineer thermogenesis into human adipocytes. In our current work, we explore the ability of human adipocytes to combust energy through alternative, UCP1-independent thermogenesis.

Dr. Michaela Keuper

Mouse metabolic phenotyping

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.

Maria Kutschke, Dr. Clarissa Barthem

Page updated

Google Sites

Report abuse