Primary cilia (PC) are antenna-like organelles that extend from the cell body into the extracellular environment, sensing signals like nutrients and hormones to inform the cell about the extracellular energy status. Primary cilia dysfunction result in ciliopathies, characterized by obesity and metabolic impairments in humans and mice.
By sensing nutritional and hormonal information and fuelling neurons with energy substrates, astrocytes play a key role in regulating systemic energy homeostasis. PC are also expressed by astrocytes, however their role in systemic metabolism regulation and obesity remains elusive.
In vitro studies in primary hypothalamic mouse astrocytes revealed that astrocyte PC length and genes were dynamically regulated by cell metabolism adaptations caused by extracellular or intracellular substrate availability. Along the same line, PC length was regulated upon high-fat diet (HFD) feeding in the arcuate nucleus of the hypothalamus. Using an inducible mouse model, allowing for depletion of PC in astrocytes of adult mice by depleting the ciliary gene intraflagellar transporter 88 (IFT88∆GFAP), we found a reduction in white adipose tissue mass, improved glucose tolerance, and increased energy expenditure in mutant compared to control mice. Similarly, we generated mice with conditional knockdown of the ciliary gene ADP Ribosylation Factor Like GTPase 13B (Arl13b∆GFAP) in GFAP-expressing astrocytes, resulting in a similar but more pronounced metabolic phenotype compared to IFT88∆GFAP mice.
These findings suggest that PC in astrocytes are regulated by nutrient availability and play a role in systemic energy homeostasis, potentially via adaptations in astrocyte cell metabolism.