COMMBAT – Communication of brown adipose tissue activity at the cellular, clinical, and societal level
This project is centered around exploring the cross talk between brown adipose tissue and brain, building on a unique combination of innovative technologies in basic research, clinical relationships and a multi-directional communication with society.
Obesity is a complex, multilayered problem that is dramatically outpacing global healthcare systems. Thus, we need to accelerate metabolic research in order to stem this crisis. Although multiple genes and critical pathways have been implicated, the field struggles to translate basic research findings to tangible therapeutic solutions in humans, and to grapple with the influences of environment and society on the successful use of these therapies. Therefore, we here aim to closely integrate cutting-edge basic research with clinical investigation and societal discourse.
Given the genetic and hormonal evidence implicating coordination between the brain and white adipose tissue as a major driver of systemic homeostasis, the scientific backbone of this flagship is to investigate the crosstalk between brown adipose tissue (BAT) and brain, and its effects on energy expenditure and feeding behavior. Active BAT is a heat-producing, energy-consuming organ. We hypothesize that a coordinated communication within BAT and to the CNS is critical for regulating systemic energy metabolism.
In parallel to investigating this new biology using novel technologies at CBMR, we will establish strategic collaborations with physicians and clinical researchers at Danish hospitals, as we believe there are rich opportunities for reciprocal benefit. We will work together with researchers at Medical Museion, and open the door to both the clinic and society for multi-directional communication, to deepen our understanding of obesity at the level of personal experience, and to bring diverse stakeholders together to discuss the questions and hopes that drive research.
COMMBAT builds on CBMR driven basic research in the intercellular crosstalk within BAT as well as the endocrine and neuronal crosstalk between BAT and brain. The purpose of this flagship is to open the door to the Danish hospitals and society to integrate unpublished clinical expertise, clinical material, as well as individual genotypes, phenotypes and experiences, with basic research questions and observations. Key collaborators include:
CBMR – Basic research pillar:
- Associate Professor Zach Gerhart-Hines
- Associate Professor Camilla Schéele
- Associate Professor Brice Emanuelli
- Professor Thue Schwartz
- Professor Ruth Loos
Medical Museion – Communication pillar:
Rigshospitalet – Clinical pillar
A decade ago, basic researchers in collaboration with clinical experts discovered that brown adipose tissue (BAT) is present in adult humans in physiologically relevant amounts. BAT is comprised of a subtype of mitochondria-rich adipocytes, which produce heat as part of a thermoregulatory system to defend body temperature. This heat production is an energy-consuming process, making BAT highly interesting as a target for obesity research.
One key element of body weight regulation is the central control of food intake based on feedback signals from peripheral organs including adipose tissue. This systems functions to defend body weight for survival, and disturbances in this communication system can affect metabolic homeostasis through altered energy expenditure or feeding behavior. We hypothesize that coordinated communication within and between thermogenic adipocytes and to the CNS is critical for regulating systemic energy metabolism.
To accelerate and elevate CBMR basic research to a level more translatable to humans, we will establish close contact with clinicians and society. Our ambition is to integrate unpublished clinical observations, clinical material and individual human genotypes and phenotypes, to inspire and direct our basic research. Finally, we hope to redirect social stigmas around fat tissue by communicating about its diversity and importance in human physiology, engaging people with the surprising story of BAT and inviting them to discuss with us the meaning, experience, and treatment of obesity. This work will be part of a wider project at Medical Museion producing stakeholder events that aim to fertilize conversation, curiosity, and new collaborations.
Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis.
Sveidahl Johansen O, Ma T, Hansen JB, Markussen LK, Schreiber R, Reverte-Salisa L, Dong H, Christensen DP, Sun W, Gnad T, Karavaeva I, Nielsen TS, Kooijman S, Cero C, Dmytriyeva O, Shen Y, Razzoli M, O'Brien SL, Kuipers EN, Nielsen CH, Orchard W, Willemsen N, Jespersen NZ, Lundh M, Sustarsic EG, Hallgren CM, Frost M, McGonigle S, Isidor MS, Broholm C, Pedersen O, Hansen JB, Grarup N, Hansen T, Kjær A, Granneman JG, Babu MM, Calebiro D, Nielsen S, Rydén M, Soccio R, Rensen PCN, Treebak JT, Schwartz TW, Emanuelli B, Bartolomucci A, Pfeifer A, Zechner R, Scheele C, Mandrup S, Gerhart-Hines Z. Cell. 2021 Jun 24;184(13):3502-3518.e33. doi: 10.1016/j.cell.2021.04.037. Epub 2021 May 27.PMID: 34048700
Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine.
Deshmukh AS, Peijs L, Beaudry JL, Jespersen NZ, Nielsen CH, Ma T, Brunner AD, Larsen TJ, Bayarri-Olmos R, Prabhakar BS, Helgstrand C, Severinsen MCK, Holst B, Kjaer A, Tang-Christensen M, Sanfridson A, Garred P, Privé GG, Pedersen BK, Gerhart-Hines Z, Nielsen S, Drucker DJ, Mann M, Scheele C. Cell Metab. 2019 Nov 5;30(5):963-975.e7. doi: 10.1016/j.cmet.2019.10.001. Epub 2019 Oct 24.PMID: 31668873
Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele C, Wolfrum C. Endocrine Reviews. 2020 Jan 1;41(1):53-65. doi: 10.1210/endrev/bnz007.PMID: 31638161
Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?
Scheele C, Henningsen JB. Annual Reviews of Physiology. 2021 Feb 10;83:279-301. doi: 10.1146/annurev-physiol-032420-042950. Epub 2020 Nov 6.
