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.

Primary cilia on muscle stem cells are critical to maintain regenerative capacity and are lost during aging

“…Mesenchymal stem and progenitor cells are broadly ciliated and play an important role in maintaining stem cell fate by regulating lineage specification, proliferation, and differentiation [50][51][52] . For example, in adipose tissue, preadipocytes are ciliated and their ablation leads to severe defects in white adipose tissue expansion 25,53 . Cilia also play a critical role in cartilage and bone development 54 .…”

A human adipose tissue cell-type transcriptome atlas

“…panels; 84 transcripts were excluded from cell-type classification due to likely co-expression (Figure 1E; Table S1, tab 4a). Gene ontology (GO) and reactome analysis of this gene list revealed over-representation of terms related to ''plasma membrane bounded cell projection organization'' (false discovery rate [FDR] 1.26 3 10 À2 ) and ''BBSome-mediated cargo targeting to cilium'' (FDR 8.09 3 10 À3 ), respectively (Table S1, tab 4b, with selected examples highlighted in Figure 1E), suggesting a possible link to the importance of primary cilia in the regulation of adipose tissue expansion (Hilgendorf, 2021;Ritter et al, 2018). In most other cases, transcripts were well separated between cell types, e.g., MC classified versus adipocyte progenitor (AP) classified (Figure 1F).…”

Primary cilia regulate adaptive responses to fasting

“…This subsequently resulted in lesser decrease in T4 and testosterone than WT. Moreover, LepR and primary cilia exist in the pre-adipocytes, therefore, these features may influence the phenotypes [17,18]. Further evaluations on other hormonal levels such as T3, rT3, GH, and IGF-1 would be useful in delineating the functional roles of primary cilia in modulating counterregulatory hormonal responses.…”