Subterranean Fishes of the World

5624

2022

AIM 2022

30

Physical inactivity – specifically the lack of moderate-to-vigorous activity – is a scourge to human health, promoting metabolic disease and muscle wasting. Interestingly, multiple ecological niches have relaxed investment into physical activity – most aptly apparent in cave-dwellers – providing unique evolutionary insight into adaptive physical inactivity. The Mexican cavefish Astyanax mexicanus has lost moderate-to-vigorous activity following cave colonization, reaching basal swim speeds ~3-fold slower than their river-dwelling counterpart. We found this comes with a remarkable shift in body composition – decreasing muscle mass by 30% and increasing fat mass by 40%. Intramyocellular analysis revealed large swaths of lipid and sugar accumulation at the expense of myofibrillar volume and contractile protein content. Transcriptomic analysis of laboratoryreared and wild-caught cavefish indicated this shift in investment is driven by increased expression of pparγ – the master regulator of adipogenesis – and a simultaneous decrease in fast myosin heavy chain expression. Ex vivo and in vivo analysis confirmed these investment strategies come with a functional trade-off – decreasing cavefish muscle fiber shortening velocity, time to maximal force, and ultimately maximal swimming velocity. Despite this, cavefish displayed a remarkable degree of muscular endurance, reaching maximal swim speeds ~3-fold faster than their basal swim speeds. Multi-omics analysis indicated carbohydrate metabolic reprogramming – specifically increased phosphoglucomutase-1 abundance and phosphorylation – as likely contributing factors, enhancing cavefish glycogen utilization under metabolically strenuous conditions. Collectively, our data reveal broad skeletal muscle reprogramming following cave colonization – displaying an adaptive cavefish phenotype reminiscent to mammalian disuse and high-fat models – while maintaining a degree of muscular endurance via metabolic reprogramming.

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