How neuronal SKN-1B influences appetite regulation and metabolism in C. elegans

Obesity has become a growing problem worldwide that subsequently leads to poor health outcomes. Signalling pathways that regulate appetite are not well understood, meaning this area of research should be explored further to uncover potential new treatments for eating disorders. The nematode worm Caenorhabditis elegans (C. elegans) is a useful model organism for quick and cost-effectiveresearch on feeding behaviour and have a high 60-80% genetic homology with humans. SKN-1 is the only functional ortholog to mammalian Nrf proteins and a previous study has found the neuronally expressed isoform SKN-1B to act via two ASI chemosensory neurons to regulate food related behaviour including satiety and exploratory behaviours.

Through a combination of techniques involving microscopy, genetics, and mimicking of a high sugar diet, this thesis explores the impact of appetite and food choices on body size, metabolism, and health. Here we show skn-1b mutants are larger than WT when fed ad libitum. Addition of glucose to the medium alters this phenotype suggesting skn-1b mutants are resistant to the effect of glucose in determining body-size. Furthermore, glucose supplementation does not lead to alteration in mitochondrial morphology of skn-1b mutants which have significantly fragmented mitochondria compared to WT. Finally, the mitochondrial fragmentation in skn-1b mutants is unlikely to be regulated by the release of Tyramine (TA) - a critical neurotransmitter for regulating food behaviour, from the ASI neurons.

Overall, research on SKN-1B along with its relevant homologs could give insight into a new role for Nrf proteins in eating behaviour and may serve as a potential new drug target for appetite dysregulation.