Jo Henningsen: "Investigations of a BAT-brain crosstalk and its capacity to regulate energy homeostasis"

Postdoc, Scheele Lab

Abstract: Brown adipose tissue (BAT) is sympathetically activated in response to cold, resulting in energy-consuming heat production. In adult humans, residual BAT is located near the CNS and is highly innervated and vascularized. Our preliminary data further suggests secretion of known neuronal growth factors from BAT.
We aim to investigate the existence of a BAT-brain crosstalk and to identify BAT-specific adipokines (batokines) with capacity to modulate central regulators of feeding and overall systemic metabolism.
From functional genomics, we have synthesized 10 proteins, 100 peptides and identified >200 genes associated with active human BAT. In an automated HTS approach, we have identified candidate batokines with capacity to induce neurite outgrowth in adrenergic human neuroblastoma. A specialized 3D co-culture system between human brown adipocytes and adrenergic neurons is being established in order to evaluate adrenergic outgrowth and innervation of brown adipocytes with genetic manipulation of selected batokines. Lastly, potential endocrine and central effects will be evaluated in cultures of human iPSC-derived hypothalamic neurons.
The expected outcome of this study is to discover novel functions of human adult BAT and to identify new treatment strategies for targeting metabolic dysfunction.