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This thesis investigates the ability of rainbow trout to modulate hepatic glucose production (Ra) and disposal (Rd). My goals were to determine: (1) if resting trout can modulate fluxes to cope with exogenous glucose; (2) how fluxes change during graded swimming; (3) how exogenous glucose affects swimming kinetics; and (4) if exogenous glucose affects cost of transport or performance. Results show that resting trout suppress Ra completely and stimulate Rd from 10.6 to 27.6 μmol kg-1 min-1. During swimming, fluxes increase from 15.6 to 21.9 μmol kg-1 min-1, but only at speeds >2.4 BL s-1. When given glucose, trout suppress Ra from 16.4 to 4.1 μmol kg-1 min-1 and stimulate Rd from 16.4 to 40.1 μmol kg-1 min-1. Glucose lowers metabolic rate but does not affect critical swimming speed. Therefore, this research shows that rainbow trout have a much better capacity for glucoregulation than generally suggested by current literature.

Rainbow trout (Oncorhynchus mykiss) is an important freshwater fish whose glucose intolerance, white muscle lactate retention and high lipolytic inertia, have interested comparative physiologists for decades. Recent advancements in mammalian G-protein coupled receptor deorphanization research have identified many endogenous metabolites as regulators of energy metabolism, including lactate and long-chain fatty acids. In addition to being essential metabolic fuels, lactate and long-chain fatty acids regulate lipolysis and lipogenesis by binding to hydroxycarboxylic acid receptor 1 (HCAR1) and the free fatty acid receptors (FFAR1 and 4), respectively. Therefore, the goal of this thesis was to quantify the effects of exogenous lactate and lipids on glucose and fatty acid mobilization in rainbow trout and identify potential signaling mechanisms by monitoring the expression and activity of key glycolytic, gluconeogenic, lipolytic, lipogenic and β-oxidation targets in the liver, muscle and adipose tissue. In Chapter 2, in vivo measurements of metabolic fuel kinetics show that lactate (i) strongly reduced hepatic glucose production by substituting glucose for lactate and (ii) exhibited no lipolytic suppression suggesting HCAR1 signaling is weak in trout. In Chapter 3, in vivo measurements of energy mobilization show that Intralipid strongly induced lipolysis by saturating circulating lipases while transcriptional induction of gluconeogenesis compensates for the acute reduction in hepatic glucose production. Intralipid infusion increased total fatty acid concentration and altered fatty acid composition while suppressing lipid metabolism of trout liver and adipose tissue. In Chapter 4, I identify the presence (hcar1 and ffar1) and absence (ffar4) of these G-protein coupled receptor genes in the rainbow trout genome and describe their evolutionary origins, using in silico approaches of microsynteny, amino acid sequence similarity and critical residue conservation. However, their importance in fish physiology remains relatively unknown, thus future studies are warranted to further investigate such metabolic signals.

Les chirurgies de type by-pass induisent des améliorations spectaculaires de l'homéostasie glucidique indépendamment de la perte de poids chez les patients obèses et diabétiques. Elles provoquent également une diminution de la préférence pour les aliments hypercaloriques. Un mécanisme proposé pour expliquer les effets sur le contrôle glucidique de ces procédures associe une diminution de la production hépatique de glucose et une augmentation de la néoglucogenèse intestinale. Les acides biliaires, décrits comme inhibiteurs de la néoglucogenèse, voient leur biodisponibilité modifiée après ces chirurgies. Ils sont en effet absents de l'anse alimentaire tandis que leur concentration est augmentée dans le sang. Nous avons donc testé l'hypothèse selon laquelle les acides biliaires plasmatiques inhiberaient la production hépatique de glucose alors que leur absence dans l'intestin induirait la néoglucogenèse intestinale. Pour cela, nous avons réalisé des dérivations biliaires chez le rat visant à reproduire le trajet de la bile dans les chirurgies de type by-pass. Nous avons montré que les dérivations biliaires entrainent une augmentation du taux circulant d'acides biliaires. Les dérivations provoquent une forte diminution de la production hépatique de glucose et une induction de la néoglucogenèse dans les portions d'intestin dépourvus de bile. Par ailleurs, la seule modification du trajet de la bile promeut une amélioration du contrôle glucidique et une diminution de l'appétence pour les aliments riches en graisse et en sucre. Ces données nous ont donc permis d'attribuer un rôle clé à la modification du trajet de la bile dans les effets bénéfiques des chirurgies de type by-pass / Gastric bypass procedures have emerged as an effective treatment for morbid obese diabetic patientssince they provoke a rapid remission of diabetes before any weight loss has occurred. Patients also report adisinterest in high calorie food. A suggested mechanism associated a decrease in hepatic glucose production toan enhanced intestinal gluconeogenesis. Bile acids, described as inhibitors of gluconeogenesis, see theirbioavailability changed after these procedures. Indeed, they are absent in the alimentary limb while theirplasmatic concentration is increased. We therefore tested the hypothesis that plasma bile acids may inhibithepatic glucose production while their absence in the gut could induce intestinal gluconeogenesis.For this, we performed bile diversions matching the modified biliary flow occurring after gastric bypassprocedures. We showed that bile diversions lead to an increase in plasma bile acids. Bile diversions promote ablunting in hepatic glucose production whereas intestinal gluconeogenesis is increased in gut segments devoidof bile. Moreover, the modification of bile routing per se improves glucose control and dramatically decreasefood intake due to an acquired disinterest in fatty food. This data shows that bile routing modification is a keymechanistic feature in the beneficial outcomes of gastric bypass procedures