Understanding the mechanisms of adaptation to altered glucose homeostasis in the blind cavefish (<i>Astyanax mexicanus</i>)

Organisms are constantly faced with changing environmental conditions, and the need to adjust their physiology to survive and thrive this constant change. Our fish species, Astyanax mexicanus, consisting of the river dwelling, surface fish and the cave dwelling, cavefish, presents an ideal model to study these adaptations. The cavefish populations have dramatically altered their metabolism, to survive prolonged starvation in cave environments. They display classic phenotypes of metabolic dysregulation such as, abnormally high appetite, increased fat storage, hyperglycemia, and decreased insulin sensitivity. Interestingly, they do not show pathologies associated with glucose dysregulation, like accumulation of harmful compounds called Advanced Glycation End-products (AGEs). AGEs form non-enzymatically when sugars combine with proteins and activate key signaling pathways associated with inflammation and tissue damage. Although this is a major pathway implicated with the progression of diabetic complications, very little is known on its underlying mechanisms. Using our unique cavefish model, we characterize the basal levels of AGEs in serum proteins of the cavefish, then explore the extent to which we can further challenge the buffering capacity of the cavefish, by inducing hyperglycemia in the cavefish. Our results highlight that some cave populations are more resistant to increasing levels of AGEs than others. Taking advantage of the fact that the cavefish are interfertile, we generate F2 hybrid populations to help us further identify the core genes within genomic regions that are associated with protein glycation using quantitative trait loci (QTL) analysis. This way improving our understanding on the key compensatory mechanisms that have evolved in the cavefish to allow them benefit from their unusual metabolism. This work is supported by the ascb International Federation for Cell Biology Scholarship This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.