The crosstalk of macrophages and the adipose tissue

Abstract

The primary cilium is a highly conserved sensory organelle found on most mammalian cells, which senses environmental signals and transduces this information into a cellular response. Within the adipocyte linage, only the adipocyte precursor cells (APCs) display a primary cilium, which is lost during differentiation. Which extracellular signals are sensed by primary ciliary signaling in APCs and how this controls preadipocyte function and differentiation is not well understood. <br/>

Tissue-resident macrophages that are formed during early embryonic development have important homeostatic functions in different tissues. In the adipose tissue (AT), adipose tissue-resident macrophages (ATMs) can be distinguished from CD11c⁺, monocyte-derived macrophages by expressing TIM4. Loss of TIM4⁺ ATMs prevents lipid accumulation in mature adipocytes, leading to restricted WAT development. This is controlled by the growth factor Pdgfcc, which is secreted by ATMs and acts on adipocytes in a paracrine manner. Strikingly, loss of the primary cilium <em>in vivo</em> also restricts WAT development. The receptor for Pdgfcc, Pdgfr-a, is located in the primary cilium, but whether macrophages communicate with adipocyte progenitor cells via the primary cilium remains unknown. <br/>

I aim to unravel the cilia-dependent communication between APCs and ATMs in the white adipose tissue. In particular, I will investigate whether paracrine signaling from macrophages acts on adipocyte precursors through signaling via the primary cilium, thereby controlling adipocyte differentiation and function. To this end, I have established an <em>in vitro</em> WAT spheroid model, which will be combined with different mouse models that display defects in primary signaling. Using this combination of 3D <em>in vitro</em> and <em>in vivo</em> approaches together with fluorescence imaging as well as biochemical and metabolic approaches, I will decipher the role of primary cilia in adipocytes – macrophage communication.