Primary Cilia Are Critical Regulators of White Adipose Tissue Expansion

Abstract

The primary cilium is a microtubule-based cellular protrusion found on most mammalian cell types in diverse tissues. It functions as a cellular antenna to sense and transduce a broad range of signals, including odorants, light, mechanical stimuli, and chemical ligands. This diversity in signals requires cilia to display a context and cell type-specific repertoire of receptors. Recently, primary cilia have emerged as critical regulators of metabolism. The importance of primary cilia in metabolic disease is highlighted by the clinical features of human genetic disorders with dysfunctional ciliary signaling, which include obesity and diabetes. This review summarizes the current literature on the role of primary cilia in metabolic disease, focusing on the importance of primary cilia in directing white adipose tissue expansion during obesity.

Keywords: adipogenesis; diabetes; obesity; primary cilia; signaling.

FIGURE 1

Schematic of the primary cilium. The cilium is composed of a microtubule-based axoneme and the surrounding ciliary membrane, which is highly enriched for receptors. The intraflagellar transport system couples to kinesin or dynein motors for anterograde or retrograde transport within the cilium. Trafficking of ciliary cargo such as receptors into or out of the primary cilium is tightly regulated and requires adaptor proteins such as TULP3 or the BBSome complex, respectively.

FIGURE 2

Ciliary signaling in pre-adipocytes. Multiple receptors localize to the pre-adipocyte primary cilium and activation of ciliary signaling pathways can either promote or inhibit adipogenesis. Specifically, Hedgehog signaling has been shown to inhibit MSC commitment to adipogenesis. In contrast, the ciliary IGF-1 receptor and ciliary FFAR4/GPR120 are expressed in committed pre-adipocytes, and activation of these ciliary signaling pathways promotes adipogenesis.