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TRR 333:  Brown and Beige Fat – Organ Crosstalk, Signaling and Energetics (BATenergy)

Subject Area Medicine
Biology
Term since 2022
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 450149205
 
Energy homeostasis is a central physiological process. If energy intake is higher than consumption, the surplus is stored primarily in adipose tissue. The pathological increase in fat mass leads to obesity, which have reached pandemic dimensions: It is estimated that 2.8 - 3.5 billion people suffer from overweight and obesity. Obesity leads to type 2 diabetes and cardiovascular disease as well as to certain types of cancer. Adipose tissues are organized in two functionally distinct types, brown adipose tissue (BAT) and white adipose tissue (WAT). In contrast to white adipocytes, brown fat cells are specialized to dissipate energy in the form of heat. In addition to classical brown adipocytes in BAT, inducible brown adipocytes, referred to as brown-in-white (brite) or beige adipocytes, reside in WAT. Together, these brown and beige adipocytes constitute the thermogenic adipose tissue, which plays an important role in systemic energy homeostasis. Importantly, human BAT activity correlates with leanness and a beneficial cardiometabolic profile. BAT is activated by the sympathetic nervous system and adrenergic signalling. However, using this pathway for pharmacological stimulation of brown/beige fat is problematic because of cardiovascular side-effects. Recent studies have described alternative signals released by energy-processing organs such as liver, muscle and gut. Another level of regulation is achieved by cells present in adipose tissue, such as endothelial or immune cells, which can secrete paracrine factors that modulate signalling pathways in thermogenic adipocytes. The picture gets even more complex because brown/beige adipocytes themselves release factors that regulate energy dissipation in an autocrine manner. Thus, there is a new emerging picture of bidirectional communication und regulation between thermogenic adipocytes and other cell types as well as between thermogenic adipose tissue and other metabolic organs. This consortium focuses on research questions related to the regulation of thermogenesis that address 1) the organ crosstalk between gut, liver, muscle and thermogenic adipose tissues, 2) the cell-cell communication within brown and beige fat, and 3) the interaction of cell organelles and intracellular signalling pathways in brown/beige adipocytes. For this purpose, advanced omics technologies, cell culture systems of murine and human adipocytes, and novel transgenic mouse models will be used to provide comprehensive molecular mechanistic insight into the regulation of thermogenic energy metabolism. Molecular mechanistic studies are performed in preclinical models under a wide range of conditions including ambient temperature and high fat diets. Subsequent to the identification of novel regulatory mechanisms, a mid- and long-term goal is to establish and to validate new therapeutic approaches for the treatment of metabolic disorders.
DFG Programme CRC/Transregios

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