Using Caenorhabditis elegans to understand appetite regulation and its associated metabolic traits

Appetite and satiety responses are key to the health and survival of an organism. These food-related behaviours require complex integration of external sensory and internal cues, and dysregulation of these can result in metabolic disorders, including obesity and its related co-morbidities. Previous studies have shown that in the nematode worm, C. elegans, a neuronal transcription factor called SKN-1B regulates appetite and satiety behaviours as well as controls metabolic and mitochondrial homeostasis (Tataridas-Pallas et al., 2021, PLoS Genetics). SKN-1B is the worm ortholog of the mammalian NF-E2 related transcription factors (Nrfs) and acts in two ASI chemosensory neurons to carry out its functions. Interestingly, our studies have also indicated that SKN-1B acts differently in hermaphrodites and males, with skn-1b mutant males exhibiting a distinct metabolic profile from that of hermaphrodites. This work explores how neuronal SKN-1B/Nrfs acts to control appetite and feeding behaviour over the life course and in a sex-specific manner, and how this impacts metabolic health and physiological parameters in whole organisms. This work could provide insight into the role of neuronally expressed Nrfs in appetite behaviours in mammalian systems, and because Nrfs are established drug targets, could be a potential therapeutic target for anti-obesity interventions.