Evolutionarily‐Conserved Mechanisms of Nutrient Acquisition in the Primordial Vertebrate, the Pacific Hagfish

Abstract

Hagfish occupy the basal position of vertebrate phylogeny and are thus of interest for studies examining the evolution of vertebrate traits. Despite a morphologically basic digestive tract, the carnivorous hagfish can rapidly and effectively acquire nutrients from which they can persist off of for upwards of 11 months. Previous studies indicate that hagfish preferentially utilize carbohydrates and transition into fat‐fuelled energy sources as fasting progresses, yet few studies examine the mechanisms by which hagfish acquire nutrients. The aim of the present study was to examine and characterize the mechanisms of nutrient acquisition in the hindgut of the Pacific hagfish (Eptatretus stoutii), focusing on one molecule from each category of macronutrients: carbohydrates (glucose), fats (oleic acid) and proteins (alanyl‐alanine). Radiotracer fluxes across intestinal tissue demonstrated concentration‐dependent uptake indicative of regulated transport, for glucose (Km 0.37 mM, Jmax 8.48 nmol/cm2/h), oleic acid (Km 55 μM, Jmax 1131 pmol/cm2/h) and alanyl‐alanine (Km 1071 μM, Jmax 70 nmol/cm2/h). Pharmacological inhibition of glucose transporters (34% decrease with 200 μM cytochalasin‐b) and sodium‐glucose linked transporters (52–83% decrease with 0.0001–1μM phlorizin) suggest mechanisms akin to those in mammals exist in the hagfish hindgut. Further similarity in transport arises in that dipeptide transport is dependent upon sodium‐proton exchange, wherein a reduced sodium environment yields a 48% decrease in transport rates. While specific isoforms of mammalian fatty acid transporters demonstrate insulin sensitivity, hagfish oleic acid transport rates were unaffected by insulin application (average rate 2741± 262 pmol/cm2/h, N=10), despite a noted 71% decrease in plasma glucose concentration. Finally, feeding resulted in significant remodeling of the intestinal mucosa with hindgut absorptive microvilli lengthening by 125% post‐feeding. Correspondingly, an increased rate of transport was noted post‐feeding, with the degree of change dependent upon the substrate type. This study reveals evolutionarily‐conserved mechanisms of nutrient transport over a broad range of substrates in the oldest extant vertebrate and solidifies the applicability of hagfish as a model for studies of early vertebrate evolution.Support or Funding InformationSupported by NSERC Discovery Grants to GG (203736) and CG (251083)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.