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Polakof S, Skiba-Cassy S, Panserat S. Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout. Am J Physiol Regul Integr Comp Physiol 297: R1769-R1776, 2009. First published September 30, 2009; doi: 10.1152/ajpregu.00369.2009.--Utilizing rainbow trout (Oncorhynchus mykiss) as a known model of a 'glucose-intolerant' and poor dietary glucose user, we assessed glucose utilization in fish chronically receiving two molecules able to improve glucose homeostasis: insulin and metformin. Our objectives were to assess the ability of rainbow trout to deal with a glucose load and to improve glucose utilization in fish receiving a chronic administration of insulin plus metformin treatments. Fish received (implanted miniosmotic pumps) saline, insulin, metformin, and insulin plus metformin solution for 4 days and then were subjected to a glucose challenge (intraperitoneal injection) to study glucose homeostasis, analyzing plasma glycemia, mRNA levels of glucose metabolism-related proteins, insulin signaling, and glycogen levels in liver and muscle. Control fish received a saline pump implantation and saline intraperitoneal injection. We found no evidence that the 'glucose intolerance' in this species could be linked to any of the molecular markers of metabolism in the tissues analyzed. By contrast, very interestingly, we show for the first time, that metformin is not only unable to improve glucose homeostasis in trout, but, in fact, its counter-acts the effects of insulin, creating an 'insulin resistance,' especially in the muscle. These results make trout an attractive original model to study both insulin and metformin effect on biological systems. fish; insulin; glucose metabolism; liver; muscle; metformin doi: 10.1152/ajpregu.00369.2009

Camivorous fish are poor users of dietary carbohydrates and are considered to be glucose intolerant. In this context, we have tested, for the first time in rainbow trout, metformin, a common anti-diabetic drug, known to modify muscle and liver metabolism and to control hyperglycemia in mammals. In the present study, juvenile trout were fed with very high levels of carbohydrates (30% of the diet) for this species during 10 days followed by feeding with pellets supplemented with metformin (0.25% of the diet) for three additional days. Dietary mefformin led to a significant reduction in postprandial glycemia in trout, demonstrating unambiguously the hypoglycemic effect of this drug. No effect of metformin was detected on mRNA levels for glucose transporter type 4 (GLUT4), or enzymes involved in glycolysis, mitochondrial energy metabolism, or on glycogen level in the white muscle. Expected inhibition of hepatic gluconeogenic (glucose-6-phosphatase, fructose1,6-bisphosphatase, and phosphoenolpyruvate carboxykinase) mRNA levels was not found, showing instead paradoxically higher mRNA levels for these genes after drug treatment. Finally, metformin treatment was associated with higher mRNA levels and activities for lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase). Overall, this study strongly supports that the induction of hepatic lipogenesis by dietary glucose may permit a more efficient control of postprandial glycemia in carnivorous fish fed with high carbohydrate diets. glucose; anti-diabetic drug; muscle; liver; carnivorous fish

Abstract This paper describes the design, implementation and research of the Cyber Sleuth Science Lab (CSSL), an innovative educational program and supporting virtual learning environment, that combines pedagogical theory, gender inclusive instruction strategies, scientific principles/practices, gamification methods, computational thinking, and real-world problem solving. This program provides underrepresented youth, especially girls, with digital forensic knowledge, skills and career pathways, challenging them to explore complex social issues related to technology and to become cyber sleuths using real-world digital forensic methods and tools to solve investigative scenarios. Students also learn about related careers while improving their cyber street smarts. The CSSL incorporates additional “outside of the computer” activities to strengthen students’ engagement such as structured in-classroom discussions, mock trials, and in-person interactions with practitioner role models. The CSSL was piloted in various forms to assess the suitability for in-school and out-of-school settings, and the students predominantly represented racial minorities. Research in this project relied on a mixed methods approach for data collection and analysis, including qualitative and quantitative methods, reinforced using learning analytics generated from the students clicking through the interface and interacting with the system. Analysis of gathered data indicate that the virtual learning environment developed in this project is highly effective for teaching digital forensic knowledge, skills, and abilities that are directly applicable in the workplace. Furthermore, the strategies for gender inclusive STEM instruction implemented in CSSL are effective for engaging girls without being harmful to boys’ engagement. Learning STEM through digital forensic science taps into girls’ motivations to address real-world problems that have direct relevance to their lives, and to protect and serve their community. After participating in the educational program, girls expressed a significantly greater increase in interest, relative to boys, in learning more about careers related to digital forensics and cybersecurity.

Based on the concept of nutritional programming in mammals, we tested whether an acute hyperglucidic-hypoproteic stimulus during first feeding could induce long-term changes in nutrient metabolism in rainbow trout. Trout alevins received during the five first days of exogenous feeding either a hyperglucidic (40% gelatinized starch + 20% glucose) and hypoproteic (20%) diet (VLP diet) or a high-protein (60%) glucose-free diet (HP diet, control). Following a common 105- day period on a commercial diet, both groups were then challenged (65 days) with a carbohydrate-rich diet (28%). Short- and long-term effects of the early stimuli were evaluated in terms of metabolic marker gene expressions and intestinal microbiota as initial gut colonisation is essential for regulating the development of the digestive system. In whole alevins (short term), diet VLP relative to HP rapidly increased gene expressions of glycolytic enzymes, while those involved in gluconeogenesis and amino acid catabolism decreased. However, none of these genes showed persistent molecular adaptation in the liver of challenged juveniles (long term). By contrast, muscle of challenged juveniles subjected previously to the VLP stimulus displayed downregulated expression of markers of glycolysis and glucose transport (not seen in the short term). These fish also had higher plasma glucose (9 h postprandial), suggesting impaired glucose homeostasis induced by the early stimulus. The early stimulus did not modify the expression of the analysed metabolism-related microRNAs, but had short- and long-term effects on intestinal fungi (not bacteria) profiles. In summary, our data show that a short hyperglucidic-hypoproteic stimulus during early life may have a long-term influence on muscle glucose metabolism and intestinal microbiota in trout. [ABSTRACT FROM AUTHOR]

There is now substantial evidence that members of the transforming growth factor-β (TGFβ family) regulate germ cell development in the mouse fetal testis. Correct development of germ cells during fetal life is critical for establishment of effective spermatogenesis and for avoiding the formation of testicular germ cell cancer in later life. Here we consider the evidence for involvement of various TGFβ family members, attempt to reconcile discrepancies and clarify what we believe to be the likely in vivo roles of these factors.

Recent findings have challenged the established concept that retinoic acid (RA) induces foetal germ cells to enter meiosis. Here, Bowles et al. identify the enzyme ALDH1A1 as a source of ovarian RA that may induce meiosis even when other RA-synthetic enzymes are deleted.

In contrast to the developing testis, molecular pathways driving fetal ovarian development have been difficult to characterise. To date no single master regulator of ovarian development has been identified that would be considered the female equivalent of Sry. Using a genomic approach we identified a number of novel protein-coding as well as non-coding genes that were detectable at higher levels in the ovary compared to testis during early mouse gonad development. We were able to cluster these ovarian genes into different temporal expression categories. Of note, Lrrc34 and AK015184 were detected in XX but not XY germ cells before the onset of sex-specific germ cell differentiation marked by entry into meiosis in an ovary and mitotic arrest in a testis. We also defined distinct spatial expression domains of somatic cell genes in the developing ovary. Our data expands the set of markers of early mouse ovary differentiation and identifies a classification of early ovarian genes, thus providing additional avenues with which to dissect this process.

Abstract In hens, the ovarian follicles committed to ovulation are arranged in an ordered follicular hierarchy. In standard broiler breeders hens genetically selected for high growth rate the reproductive function is clearly dysfunctional. Feed restriction is needed during reproductive development to limit the formation of excessive numbers of ovarian yellow follicles arranged in multiple hierarchies. To determine whether leptin is involved in the nutritional and reproductive interactions controlling follicular hierarchy in hens, blood leptin levels and ovarian expression of the leptin receptor mRNA were determined during follicle maturation in three chicken lines; a slow growing broiler "Label" genotype without reproductive dysfunction, a fast growing "Standard" genotype fed ad libitum or restricted and a fast growing "Experimental" line with intermediate reproductive performance levels. Whereas expression of the leptin receptor mRNA did not change in the theca, it clearly decreased with follicular differentiation in the granulosa of slow growing hens. In fast growing standard hens fed ad libitum and presenting significant reproductive dysfunction, the decrease was disrupted and dramatic up-regulation of granulosa cell expression of the leptin receptor was observed. On the other hand, feed restriction decreased the overall level of expression of the leptin receptor mRNA and restored the decrease with follicular growth. The level of expression of the leptin receptor probably modulates the action of leptin on follicular differentiation. Since blood leptin and other metabolic factors were not affected by the genotype or by nutritional state, the factors involved in the regulation of leptin receptor gene expression remain to be determined. This study demonstrates the involvement of leptin in the nutritional control of reproduction in birds. Leptin action on the ovary probably controls follicular hierarchy through the regulation of steroidogenesis.

Supplementing a fishmeal-free diet with yeast extract improves rainbow trout (Oncorhynchus mykiss) growth performance and modulates the hepatic and intestinal transcriptomic response. These effects are often observed in the long term but are not well documented after short periods of fasting. Fasting for a few days is a common practice in fish farming, especially before handling the fish, such as for short sorting, tank transfers, and vaccinations. In the present study, rainbow trout were subjected to a 4-day fast and then refed, for 8 days, a conventional diet containing fishmeal (control diet) or alternative diets composed of terrestrial animal by-products supplemented or not with a yeast extract. During the refeeding period alone, most of the parameters considered did not differ significantly in response to the different feeds. Only the expression of claudin-15 was upregulated in fish fed the yeast-supplemented diet compared to the control diet. Conversely, fasting followed by refeeding significantly influenced most of the parameters analyzed. In the proximal intestine, the surface area of villi significantly increased, and the density of goblet cell tended to decrease during refeeding. Although no distinct plasma immune response or major signs of gut inflammation were observed, some genes involved in the structure, complement pathway, antiviral functions, coagulation, and endoplasmic reticulum stress response of the liver and intestine were significantly regulated by refeeding after fasting. These results indicate that short-term fasting, as commonly practiced in fish farming, significantly alters the physiology of the liver and intestine regardless of the composition of the diet., (© 2024. The Author(s).)

The present study aims to investigate nutritional programming through early starvation in the European seabass (Dicentrarchus labrax). European seabass larvae were fasted at three different developmental periods for three durations from 60 to 65 dph (F1), 81 to 87 dph (F2), and 123 to 133 dph (F3). Immediate effects were investigated by studying gene expression of npy (neuropeptide Y) and avt (Arginine vasotocin) in the head, while potential long-term effects (i.e., programming) were evaluated on intermediary metabolism later in life (in juveniles). Our findings indicate a direct effect regarding gene expression in the head only for F1, with higher avt mRNA level in fasted larved compared to controls. The early starvation periods had no long-term effect on growth performance (body weight and body length). Regarding intermediary metabolism, we analyzed related key plasma metabolites which reflect the intermediary metabolism: no differences for glucose, triglycerides, and free fatty acids in the plasma were observed in juveniles irrespective of the three early starvation stimuli. As programming is mainly linked to molecular mechanisms, we then studied hepatic mRNA levels for 23 key actors of glucose, lipid, amino acid, and energy metabolism. For many of the metabolic genes, there was no impact of early starvation in juveniles, except for three genes involved in glucose metabolism (glut2-glucose transporter and pk-pyruvate kinase) and lipid metabolism (acly-ATP citrate lyase) which were higher in F2 compared to control. Together, these results highlight that starvation between 81 to 87 dph may have more long-term impact, suggesting the existence of a developmental window for programming by starvation. In conclusion, European seabass appeared to be resilient to early starvation during larvae stages without drastic impacts on intermediary metabolism later in life., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Arachidonic acid (C20: 4n-6, AA) plays a fundamental role in fish physiology, influencing growth, survival and stress resistance. However, imbalances in dietary AA can have detrimental effects on fish health and performance. Optimal AA requirements for rainbow trout have not been established. This study aimed to elucidate the effects of varying dietary AA levels on survival, growth, long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic capacity, oxylipin profiles, lipid peroxidation, and stress resistance of rainbow trout fry. Over a period of eight weeks, 4000 female rainbow trout fry at the resorptive stage (0.12 g) from their first feeding were fed diets with varying levels of AA (0.6%, 1.1% or 2.5% of total fatty acids) while survival and growth metrics were closely monitored. The dietary trial was followed by an acute confinement stress test. Notably, while the fatty acid profiles of the fish reflected dietary intake, those fed an AA-0.6% diet showed increased expression of elongase5, highlighting their inherent ability to produce LC-PUFAs from C18 PUFAs and suggesting potential AA or docosapentaenoic acid n-6 (DPA n-6 ) biosynthesis. However, even with this biosynthetic capacity, the trout fed reduced dietary AA had higher mortality rates. The diet had no effect on final weight (3.38 g on average for the three diets). Conversely, increased dietary AA enhanced eicosanoid production from AA, suggesting potential inflammatory and oxidative consequences. This was further evidenced by an increase in non-enzymatic lipid oxidation metabolites, particularly in the AA-2.5% diet group, which had higher levels of phytoprostanes and isoprostanes, markers of cellular oxidative damage. Importantly, the AA-1.1% diet proved to be particularly beneficial for stress resilience. This was evidenced by higher post-stress turnover rates of serotonin and dopamine, neurotransmitters central to the fish's stress response. In conclusion, a dietary AA intake of 1.1% of total fatty acids appears to promote overall resilience in rainbow trout fry., (© 2024. The Author(s).)

Background: High dietary carbohydrates can spare protein in rainbow trout (Oncorhynchus mykiss) but may affect growth and health. Inulin, a prebiotic, could have nutritional and metabolic effects, along with anti-inflammatory properties in teleosts, improving growth and welfare. We tested this hypothesis in rainbow trout by feeding them a 100% plant-based diet, which is a viable alternative to fishmeal and fish oil in aquaculture feeds. In a two-factor design, we examined the impact of inulin (2%) as well as the variation in the carbohydrates (CHO)/plant protein ratio on rainbow trout. We assessed the influence of these factors on zootechnical parameters, plasma metabolites, gut microbiota, production of short-chain fatty acids and lactic acid, as well as the expression of free-fatty acid receptor genes in the mid-intestine, intermediary liver metabolism, and immune markers in a 12-week feeding trial., Results: The use of 2% inulin did not significantly change the fish intestinal microbiota, but interestingly, the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity, with 21 bacterial genera affected, including Ralstonia, Bacillus, and 11 lactic-acid producing bacteria. There were higher levels of butyric, and valeric acid in groups fed with high CHO/protein diet but not with inulin. The high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines (il1b, il8, and tnfa) in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine (tjp1a and tjp3). However, the 2% inulin did not modify the expression of plasma immune markers. Finally, inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates., Conclusions: With a 100% plant-based diet, inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2% inulin does not appear to improve the use of CHO when combined with a 100% plant-based diet., (© 2024. The Author(s).)

Taste plays a fundamental role in an animal’s ability to detect nutrients and transmits key dietary information to the brain, which is crucial for its growth and survival. Providing alternative terrestrial ingredients early in feeding influences the growth of rainbow trout (RT, Oncorhynchus mykiss ). Thus, the present study aimed to assess the influence, via long-term feeding (from the first feeding to 8 months), of alternative plant ingredients (V diet for vegetable diet v. C diet for a control diet) in RT on the mechanism of fat sensing at the gustatory level. After the feeding trial, we studied the pathways of the fat-sensing mechanism in tongue tissue and the integrated response in the brain. To this end, we analysed the expression pattern of free fatty acid receptors ( ffar ) 1 and 2, markers of calcium-signalling pathways (phospholipase C β , Orai, Stim or Serca), the serotonin level (a key neurotransmitter in taste buds) and the expression pattern of appetite-regulating neuropeptides in the hypothalamus (central area of appetite regulation). The results revealed that the V diet modified the expression pattern of ffar1 and paralogs of ffar2 genes in tongue tissue, along with differential regulation of calcium-signalling pathways and a defect in serotonin level and brain turnover, without influencing neuropeptide expression. This study is the first to support that changes in feeding behaviour of RT fed a V diet could be due to the difference in nutrient sensing and a decrease in hedonic sensation. We revealed that RT have similar fat-detection mechanisms as mammals.

The formulation of sustainable fish feeds based on plant ingredients supplemented by alternative ingredients to plant (insect, micro-algae, yeast) and genetic selection of fish for plant-based diets were tested on rainbow trout in two separate experiments. Plant-based diets and corresponding diets supplemented with an ingredient mix: insect, micro-algae and yeast in Experiment A, and insect and yeast in Experiment B were compared to commercial-like diets. In experiment A, the mix-supplemented diet was successful in compensating the altered growth performance of fish fed their respective plant-based diet compared to those fed the commercial diet, by restoring feed conversion. In experiment B, the selected line demonstrated improved growth performances of fish fed mix-supplemented and plant-based diets compared to the non-selected line. Metabolomics demonstrated a plasma compositional stability in fish fed mix-supplemented and basal plant-based diets comprising an amino acid accumulation and a glucose depletion, compared to those fed commercial diets. The selected line fed mix-supplemented and commercial diets showed changes in inositol, ethanol and methanol compared to the non-selected line, suggesting an involvement of microbiota. Changes in plasma glycine-betaine content in fish fed the mix-supplemented diet suggest the ability of the selected line to adapt to alternative ingredients., (© 2023. The Author(s).)

Stresses associated with changes in diet or environmental disturbances are common situations that fish encounter during their lifetime. The stability and ease of measuring microRNAs (miRNAs) present in biological fluids make these molecules particularly interesting biomarkers for non-lethal assessment of stress in animals. Rainbow trout were exposed for four weeks to abiotic stress (moderate hypoxia) and/or nutritional stress (a high-carbohydrate/low-protein diet). Blood plasma and epidermal mucus were sampled at the end of the experiment, and miRNAs were assessed using small RNA sequencing. We identified four miRNAs (miR-122-5p, miR-184-3p, miR-192-5p and miR-194a-5p) and three miRNAs (miR-210-3p, miR-153a-3p and miR-218c-5p) that accumulated in response to stress in blood plasma and epidermal mucus, respectively. In particular, the abundance of miR-210-3p, a hypoxamiR in mammals, increased strongly in the epidermal mucus of rainbow trout subjected to moderate hypoxia, and can thus be considered a relevant biomarker of hypoxic stress in trout. We explored the contribution of 22 tissues/organs to the abundance of circulating miRNAs (c-miRNAs) in blood plasma and epidermal mucus influenced by the treatments. Some miRNAs were tissue-specific, while others were distributed among several tissues. Some c-miRNAs (e.g., miR-210-3p, miR184-3p) showed similar variations in both tissues and fluids, while others showed an inverse trend (e.g., miR-122-5p) or no apparent relationship (e.g. miR-192-5p, miR-194a-5p. Overall, these results demonstrate that c-miRNAs can be used as non-lethal biomarkers to study stress in fish. In particular, the upregulation of miR-210-3p in epidermal mucus induced by hypoxia demonstrates the potential of using epidermal mucus as a matrix for identifying non-invasive biomarkers of stress. This study provides information about the tissue sources of c-miRNAs and highlights the potential difficulty in relating variations in miRNA abundance in biological fluids to that in tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Physical enrichment is known to improve living conditions of fish held in farming systems and has been shown to promote behavioral plasticity in captive fish. However, the brain's regulatory-mechanism systems underlying its behavioral effects remain poorly studied. The present study investigated the impact of a three-month exposure to an enriched environment (EE vs. barren environment, BE) on the modulation of brain function in rainbow trout ( Oncorhynchus mykiss ) juveniles. Using high-throughput RT-qPCR, we assessed mRNA genes related to brain function in several areas of the trout brain. These included markers of cerebral activity and plasticity, neurogenesis, synaptogenesis, or selected neurotransmitters pathways (dopamine, glutamate, GABA, and serotonin). Overall, the fish from EE displayed a series of differentially expressed genes (neurotrophic, neurogenesis, and synaptogenesis markers) essentially localized in the telencephalon, which could underpin the beneficial effects of complexifying the environment on fish brain plasticity. In addition, EE significantly affected blood plasma c-miRNA signatures, as revealed by the upregulation of four c-miRNAs (miR-200b/c-3p, miR-203a-3p, miR-205-1a-5p, miR-218a-5p) in fish blood plasma after 185 days of EE exposure. Overall, we concluded that complexifying the environment through the addition of physical structures that stimulate and encourage fish to explore promotes the trout's brain function in farming conditions.

Background: The broodstock diet, and in particular the lipid and fatty acid composition of the diet, is known to play a key role in reproductive efficiency and survival of the progeny in fish. A major problem when replacing both fish meal and fish oil by plant sources is the lack of n-3 long chain polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To address this problem, we studied the effect of the plant-based diet supplemented with Schizochytrium sp. microalgae, source of DHA, compared to a conventional commercial diet rich in fish meal and fish oil on reproductive performance and egg quality and the consequences on progeny, in female rainbow trout broodstock., Results: The results demonstrated that DHA-rich microalgae supplementation in a plant-based diet allowed for the maintenance of reproductive performance and egg quality comparable to a conventional commercial feed rich in fish meal and fish oil and led to an increased significant fry survival after resorption. Moreover, when females were fed a plant-based diet supplemented with micro-algae, the 4-month-old progenies showed a significant higher growth when they were challenged with a similar diet as broodstock during 1 month. We provide evidence for metabolic programming in which the maternal dietary induced significant protracted effects on lipid metabolism of progeny., Conclusions: The present study demonstrates that supplementation of a plant-based diet with DHA-rich microalgae can be an effective alternative to fish meal and fish oil in rainbow trout broodstock aquafeed., (© 2022. The Author(s).)

Background: Circulating miRNAs (c-miRNAs) are found in most, if not all, biological fluids and are becoming well-established non-invasive biomarkers of many human pathologies. However, their features in non-pathological contexts and whether their expression profiles reflect normal life history events have received little attention, especially in non-mammalian species. The aim of the present study was to investigate the potential of c-miRNAs to serve as biomarkers of reproductive and metabolic states in fish., Results: The blood plasma was sampled throughout the reproductive cycle of female rainbow trout subjected to two different feeding regimes that triggered contrasting metabolic states. In addition, ovarian fluid was sampled at ovulation, and all samples were subjected to small RNA-seq analysis, leading to the establishment of a comprehensive miRNA repertoire (i.e., miRNAome) and enabling subsequent comparative analyses to a panel of RNA-seq libraries from a wide variety of tissues and organs. We showed that biological fluid miRNAomes are complex and encompass a high proportion of the overall rainbow trout miRNAome. While sharing a high proportion of common miRNAs, the blood plasma and ovarian fluid miRNAomes exhibited strong fluid-specific signatures. We further revealed that the blood plasma miRNAome significantly changed depending on metabolic and reproductive states. We subsequently identified three evolutionarily conserved muscle-specific miRNAs or myomiRs (miR-1-1/2-3p, miR-133a-1/2-3p, and miR-206-3p) that accumulated in the blood plasma in response to high feeding rates, making these myomiRs strong candidate biomarkers of active myogenesis. We also identified miR-202-5p as a candidate biomarker for reproductive success that could be used to predict ovulation and/or egg quality., Conclusions: Together, these promising results reveal the high potential of c-miRNAs, including evolutionarily conserved myomiRs, as physiologically relevant biomarker candidates and pave the way for the use of c-miRNAs for non-invasive phenotyping in various fish species., (© 2021. The Author(s).)

Within the context of a growing aquaculture production coupled with a plateau of the production in the main components of aquafeeds (fish oil and fishmeal), recent studies have typically focused on replacing these feedstuffs with terrestrial plant ingredients for cultured carnivorous aquatic species, such as rainbow trout ( Oncorhynchus mykiss ). Substitution rates without adverse effects have, however, reached their limit. One potential way forward would be to take advantage of the genetic variability that exists in the salmonid population. However, to date, little is known about the underlying molecular mechanisms responsible for this genetic variability. The aim of the present research was to understand why some genotypes are better able to utilize plant-based diets devoid of marine resources. In this regard, three isogenic lines of rainbow trout (R23h, AB1h, and A22h), with similar growth when fed marine resources-based diets and which differ greatly in their responses to a plant-based diet, were fed with either a complete plant-based diet (V diet) or a marine resources-based diet (M diet) since first-feeding. Fish traits and the hepatic transcriptome of these three genotypes were compared after 5 months of feeding. First, differences in the ability to grow with the V diet observed amongst genotypes was not due to higher feed intake, but instead due to differences in feed efficiency. The comparison of transcriptome profiles revealed 575 (R23h vs. AB1h), 1,770 (R23h vs. A22h), and 2,973 (AB1h vs. A22h) probes differentially expressed amongst the three genotypes when fed the V diet. Interestingly, R23h and AB1h fish, which were the least affected by the V diet, exhibited the highest growth. These results demonstrate that these fish were able to maintain a high level of energy production and protein synthesis. Moreover, these genotypes were also able to activate pathways linked to lipid and cholesterol metabolisms, such as the biosynthesis of long-chain polyunsaturated fatty acids. Finally, as previously, immunity seems to also play an important role in the ability of fish to use the V diet, and further studies are needed to understand the mechanisms by which immunity interacts with growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Callet, Dupont-Nivet, Danion, Burel, Cluzeaud, Surget, Aguirre, Kerneis, Labbé, Panserat, Quillet, Geurden, Skiba-Cassy and Médale.)

Background: Farmed fish food with reduced fish-derived products are gaining growing interest due to the ecological impact of fish-derived protein utilization and the necessity to increase aquaculture sustainability. Although different terrestrial plant proteins could replace fishmeal proteins, their use is associated with adverse effects. Here, we investigated how diets composed of terrestrial vegetal sources supplemented with proteins originating from insect, yeast or terrestrial animal by-products affect rainbow trout (Onchorynchus mykiss) gut microbiota composition, growth performance and resistance to bacterial infection by the fish pathogen Flavobacterium psychrophilum responsible for frequent outbreaks in aquaculture settings., Results: We showed that the tested regimes significantly increased gut bacterial richness compared to full vegetal or commercial-like diets, and that vegetal diet supplemented with insect and yeast proteins improves growth performance compared to full vegetal diet without altering rainbow trout susceptibility to F. psychrophilum infection., Conclusion: Our results demonstrate that the use of insect and yeast protein complements to vegetal fish feeds maintain microbiota functions, growth performance and fish health, therefore identifying promising alternative diets to improve aquaculture's sustainability.

Background: Plant raw materials are commonly used in aquafeeds, as marine resources are unsustainable. However, full plant-based diets lead to poorer fish growth performance., Objective: We aimed to understand the metabolic effects of a yeast fraction as a protein supplement in a plant-based diet and to integrate such effects with phenotypic traits as a new approach to assess the interest of this raw material., Methods: Juvenile (49 g) rainbow trout (Oncorhynchus mykiss) were fed graded levels of a yeast protein-rich fraction (5% YST05, 10% YST10, 15% YST15) in a plant-based diet (PB) for 84 d. Final body weight, feed conversion ratio, and hepatosomatic and viscerosomatic indexes were measured. Plasma, liver, and muscle 1H-NMR fingerprints were analyzed with principal component analyses, and their metabolite patterns were clustered according to the yeast level to identify concomitant metabolic effects. A regression modeling approach was used to predict tissue metabolite changes from plasma fingerprints., Results: In tissues, the patterns of metabolite changes followed either linear trends with the gradual inclusion of a yeast fraction (2 patterns out of 6 in muscle, 1 in liver) or quadratic trends (4 patterns in muscle, 5 in liver). Muscle aspartate and glucose (395 and 138% maximum increase in relative content compared with PB, respectively) revealing modification in energy metabolism, as well as modification of liver betaine (163% maximum increase) and muscle histidine (57% maximum decrease) related functions, indicates that the yeast fraction could improve growth in several ways. The highest correlation between measured and predicted metabolite intensities in a tissue based on plasma fingerprints was observed for betaine in liver (r = 0.80)., Conclusions: These findings herald a new approach to assess the plurality of metabolic effects induced by diets and establish the optimal level of raw materials. They open the way for using plasma as a noninvasive matrix in trout nutrition studies., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)