Investigating SKN-1B-mediated appetite behaviours in Caenorhabditis elegans males.

The rising prevalence of obesity in modern societies is straining healthcare systems and significantly impacting the health and wellbeing of affected individuals. Understanding the genetic basis of appetite-related behaviours is crucial for developing more effective, personalised medical interventions for obesity, especially when considering sex-specific differences. Caenorhabditis elegans serves as an excellent model organism for studying these behaviours due to its genetic similarity to humans, sharing approximately 60% of homologous genes, and its ability to generate substantial data efficiently because of its short developmental and lifespans. Its appetite-related behaviours parallel those observed in mammals, making it a valuable tool for advancing our knowledge and treatment strategies for obesity.

In Caenorhabditis elegans, the molecule SKN-1B is expressed specifically in the ASI chemosensory neurons, which carry out functions akin to the mammalian hypothalamus. In hermaphrodite Caenorhabditis elegans, SKN-1B has been shown to regulate feeding and exploratory behaviours in response to food, but its effect on male appetite behaviours does not seem as pronounced and is less understood. Characterising sex-specific differences in eating behaviour at a molecular level is important for understanding how approaches to managing appetite regulation need to be uniquely adjusted for men and women.

This project finds that skn-1b mutant males become satiated quicker than wildtype males, leaving food earlier and with a greater capacity to explore their surroundings for a mate, presenting new evidence for the role of SKN-1B in appetite regulation and energy metabolism in a sex-specific manner. As the ortholog of the mammalian Nrf transcription factors, SKN-1B's role in regulating appetite underscores its potential as a therapeutic target for human obesity treatment development.

In addition, the expression pattern of another SKN-1 isoform, SKN-1D, was found to be both overlapping and distinct from SKN-1B, suggesting potential shared roles relating to appetite regulation and possible influence on current and past research investigating SKN-1B.

Collectively, these findings highlight the importance of 1) precisely characterising SKN-1B influenced appetite behaviours to distinguish it from other isoforms, and 2) considering biological sex differences when developing more personalised approaches in the treatment of overweight and obesity.