Dietary Amino Acid Imbalance Research Articles

Intestinal GCN2 controls Drosophila systemic growth in response to Lactiplantibacillus plantarum symbiotic cues encoded by r/tRNA operons.

Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically defined diets, we found that association with Lp improves the growth of larvae-fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its host's growth through a molecular dialogue that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the general control nonderepressible 2 (GCN2) kinase in Drosophila's enterocytes. Our data indicate that Lp's r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialogue between host and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

SummaryGDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.

Partial and total replacement of fishmeal by a blend of animal and plant proteins in diets forSeriola dumerili: Effects on performance and nutrient efficiency

A 154‐day trial was performed to assess the use of an alternative protein blend (corn gluten, krill and meat meal) as a substitute for fishmeal in diets for juvenile yellowtail, using four isolipidic (140 g/kg) and isoenergetic diets (24 MJ/kg) with the same digestible protein content (50%). The control diet was FM100, without replacement, and in FM66, FM33 and FM0, fishmeal was replaced at 33 g/kg, 66 g/kg and 100 g/kg, respectively. At the end of the experiment, no differences in growth parameters were observed. Fish fed the FM0 diet exhibited the lowest survival (23%). This high mortality may be due to different factors, such as a dietary amino acid imbalance or some antinutrient factors contained in the alternative ingredients. Feed intake, feed conversion ratio, digestible protein intake and protein efficiency ratio were similar in all diets. However, digestible energy intake and protein efficiency retention were lowest in fish fed the FM0 diet. Apparent digestibility coefficients for protein, energy and amino acids diminished as a substitution for fishmeal increased. Significant differences were observed in the diet whole‐fish body profile amino acid retention (AAR) ratio for the seven essential amino acids. In summary, total fishmeal replacement by the blend assayed was not feasible for yellowtail. The FM66 diet resulted in good growth, high survival and good nutrient efficiency.

Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.

Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4), the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α) phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways.

Oxygen Consumption Constrains Food Intake in Fish Fed Diets Varying in Essential Amino Acid Composition

Compromisation of food intake when confronted with diets deficient in essential amino acids is a common response of fish and other animals, but the underlying physiological factors are poorly understood. We hypothesize that oxygen consumption of fish is a possible physiological factor constraining food intake. To verify, we assessed the food intake and oxygen consumption of rainbow trout fed to satiation with diets which differed in essential amino acid (methionine and lysine) compositions: a balanced vs. an imbalanced amino acid diet. Both diets were tested at two water oxygen levels: hypoxia vs. normoxia. Trout consumed 29% less food under hypoxia compared to normoxia (p<0.001). Under both hypoxia and normoxia trout significantly reduced food intake by 11% and 16% respectively when fed the imbalanced compared to the balanced amino acid diet. Oxygen consumption of the trout per unit body mass remained identical for both diet groups not only under hypoxia but also under normoxia (p>0.05). This difference in food intake between diets under normoxia together with the identical oxygen consumption supports the hypothesis that food intake in fish can be constrained by a set-point value of oxygen consumption, as seen here on a six-week time scale.

Appropriate amino acid mixtures for tryptophan depletion and tyrosine/phenylalanine depletion and the safety of long-term amino acid depletion in humans

AbbreviationsATD Acute tryptophan depletionAPTD Acute tyrosine/phenylalanine depletionGMP GlycomacropeptideTrp TryptophanTyr TyrosinePhe PhenylalanineDOPA dihydroxyphenylalanineDear Editor,In a recent review in this journal, Badawy ( 2013) discussedthe appropriate composition of amino acid mixtures for acutetryptophan depletion (ATD) and acute phenylalanine/tyrosinedepletion(APTD)studiesandsuggestedthatglycomacropeptide(GMP), which contains no aromatic amino acids, may be asuitable protein to use in acute depletion studies and long-termATD and APTD treatments of patients with mania and schizo-phrenia. The review raises a number of interesting issues but hasaspects that are problematic.1. The review suggests that GMP may be an effective nutri-tionaltherapyformanicand psychoticdisorders.Howev-er,thereviewdoesnotraisetheissueofwhetheraproteinwill necessarily be free of adverse effects. GMP lacksaromatic amino acids and, if given chronically, wouldcause the intake of amino acids to be imbalanced. Aspointed out by Young (2008), the extensive animal liter-ature on the effects of imbalanced amino acid diets indi-cates adverse effects including reductions in food intake,growth retardation, and the development of fatty liver.Furthermore, tyrosine (Tyr) and tryptophan (Trp) areessentialaminoacids,anddepletingthemmayhavesubtleeffectsonproteinsynthesis.Thepossibleimplicationsforbrain function of long-term mild disturbances of proteinsynthesisarenotknown.Rulingoutanyadverseeffectsoflong-term ATD or APTD in humans would be difficult,andanylong-termdepletionstudyinhumans,usingeitheramino acid mixtures or a protein such as GMP, would behard to justify ethically.2. The review mentions that GMP is lacking in histidine.This means that GMP would be expected to depletehistidine levels, but the implications of this are not men-tioned. In rats, histidine levels influence brain histaminelevels more than Trp levels influence brain serotoninlevels, and acute histidine depletion in humans, using ahistidine-deficient amino acid mixture, has behavioral ef-fects (van Ruitenbeek et al. 2009). Therefore, if GMP isused for acute ATD or APTD studies, histidine should beaddedtotheGMPinbothdepletionandcontrolconditionsto avoid a study on the combined effects of low histamineand low serotonin or low histamine and low dopamine.3. The review suggests that GMP may be useful for treatingmania by depleting dopamine. This is based on the studyof Scarna et al. (2003) who found a therapeutic effect,relativeto placebo, of giving a mixture of branchedchainamino acids (BCAA) to manic patients everyday for7 days. The effect was attributed to lowered dopamine,as the BCAA will inhibit the uptake of phenylalanine(Phe) and Tyr into the brain. However, the BCAA willalso inhibit the uptake of Trp into the brain. Two studiessuggest that depletion of Trp may have played a moreimportant role than depletion of Phe and Tyr in the ther-apeutic effect of the BCAA. Firstly, the Tyr hydroxylaseinhibitor α-methylparatyrosine had no consistent effecton the symptoms of manic patients (Bunney et al. 1971).Secondly,ATDimprovedthesymptomsofmanicpatientsmore than treatment with a placebo (Applebaum et al.2007). Therefore, if GMP has an effect on manic

Homeostatic regulation of protein intake: in search of a mechanism

Free-living organisms must procure adequate nutrition by negotiating an environment in which both the quality and quantity of food vary markedly. Recent decades have seen marked progress in our understanding of neural regulation of feeding behavior. However, this progress has occurred largely in the context of energy intake, despite the fact that food intake is influenced by more than just the energy content of the diet. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake. High-protein diets tend to reduce intake, low-protein diets tend to increase intake, and rodent models seem to self-select between diets in order to meet protein requirements and avoid diets that are imbalanced in amino acids. Recent work suggests that the amino acid leucine regulates food intake by altering mTOR and AMPK signaling in the hypothalamus, while activation of GCN2 within the anterior piriform cortex contributes to the detection and avoidance of amino acid-imbalanced diets. This review focuses on the role that these and other signaling systems may play in mediating the homeostatic regulation of protein balance, and in doing so, highlights our lack of knowledge regarding the physiological and neurobiological mechanisms that might underpin such a regulatory phenomenon.

Identification of GCN2 as new redox regulator for oxidative stress prevention in vivo

Constitution of oxidative defense systems and, correspondingly, oxidative stress prevention are highly dependent on amino acid supply. In vitro, experiments have demonstrated that amino acid availability participates to the homeostasis of reactive oxygen species. However the molecular mechanisms involved in the maintenance of redox homeostasis responsive to circulating amino acid levels remain unclear. As GCN2 is a protein kinase considered to be an important sensor for amino acids availability and a potential regulator of redox homeostasis, we hypothesized that this kinase can modulate redox homeostasis in vivo, in response to an amino acid-imbalanced diet.We investigated the response of GCN2+/+ and GCN2−/− mice to a long-term (24weeks) leucine-imbalanced diet (EDΔLeu). In order to evaluate the oxidation level in each group of mice, we determined the degree of protein oxidation in the liver. Interestingly, GCN2−/− mice exhibited an increase in protein carbonylation, a marker of oxidative stress, in response to the EDΔLeu diet. These data correlate with a decrease in hepatic GPX1 expression, a major antioxidant enzyme, and a decrease in total GPX activity in the liver. Our results suggest that GCN2 and its downstream signaling pathway have an important role in the protection against oxidative injuries induced by an amino acid-imbalanced diet, and that it can play a critical role in the prevention of oxidative damage.

The amino acid sensor GCN2 biases macronutrient selection during aging.

Selection of a balanced diet has a determinant impact on human health. Individual food preferences involve socio-cultural as well as physiological factors and evolve during aging. In mammals, physiological mechanisms governing food choices appear to require the sensing of nutrient concentrations in diet. This is particularly the case for dietary amino acids that are sensed by the protein kinase GCN2. It has been reported that GCN2 is involved in the adaptive response to amino acid imbalanced diets at the level of food intake and lipid metabolism. Here, we hypothesized that GCN2 may play a role in macronutrient selection and its age-related changes. Two groups of wild-type and GCN2 knock-out mice were subjected to a food self-selection protocol at ages 6, 12, 18 and 24months. During each test, mice were allowed to create their own diets by selecting between three separate food sources, each containing either protein, fat or carbohydrates. Our results show that the absence of GCN2 had two main age-related effects. First, it exacerbated fat preference at the expense of carbohydrate consumption. Second, it prevented the increase in protein intake. These findings indicate that, in omnivores, the GCN2 ancient pathway participates in the control of food preference.

Effect of lysine and tyrosine supplementation in the amino acid metabolism of Diplodus sargus larvae fed rotifers

Dietary amino acid imbalances are likely to happen when fish larvae are fed live food. This can lead to reduced growth as well as decreased larval quality. The tube-feeding technique can be used to assess the effect of free amino acid supplementation at short term and determine whether a given amino acid is deficient in the diet. In this study supplementation of lysine and tyrosine were tested in Diplodus sargus larvae fed rotifers in order to determine its effect on the metabolism of these amino acids. Supplementation was done using rotifers enriched with liposomes boosted with free amino acids. Single crystalline 14C amino acids as well as a mixture of 14C amino acids were used as tracers to compare results of individual amino acid metabolism with the average of all amino acids. The results showed low absorption efficiencies for both tyrosine and lysine when compared to the average of all amino acids. A lower relative 14C retention was found when D. sargus larvae were fed tyrosine enriched rotifers and tube-fed 14C tyrosine, indicating that tyrosine was not a limiting amino acid. On the other hand, lysine supplementation had a similar retention percentage in the treatments with and without lysine supplementation. Based on the tube-feeding studies with lysine and tyrosine supplementated rotifers neither lysine nor tyrosine affected protein synthesis in a way to indicate that these amino acids are insufficient in D. sargus larvae fed rotifers.

The effect of dietary indispensable amino acid imbalances on feed intake: Is there a sensing of deficiency and neural signaling present in fish?

Most studies on amino acid imbalance and dietary selectivity in fish have been conducted using mammalian models. In rats, amino acid deficiencies cause a rapid, within minutes, decrease in food intake. In comparison, teleost fish have no aversion to indispensable amino acid-devoid diets, although possible taste aversion was not distinguished from neurological feedback. Therefore, it remains to be answered if amino acid attractant(s) can override neurological responses to amino acid deficiency in the diet. We report here for the first time the effects of dietary amino acid imbalances on the diet intake, and survival and growth response in a juvenile cichlid, midas ( Amphilophus citrinellum). In the first experiment, a protein-based, a free amino acid-based diet (Free AA) and two indispensable amino acid (IDAA) devoid diets were tested. Fish responded initially by a decreased feed intake, but two weeks into the experiment, a significantly increased intake of the amino acid imbalanced diets was observed. In the second experiment, free amino acid imbalanced diets were offered to the fish using four different feeding strategy/treatments. These strategies were based on frequency of feeding imbalanced diets that changed from “different diet in every meal” to “different diet each other day”. However, every two days the amount of IAA provided to all groups was identical. Fish in all feeding treatments increased their body weight significantly, but their final weights decreased linearly with lower frequency of complimentary diet provision. There were significant differences in diet utilization when expressed as feed conversions. However, the most significant results demonstrated that weight gains calculated on the weekly basis improved significantly in all imbalanced/complimentary diet treatment groups. It is hypothesized that due to their high tolerance to amino acid imbalances, fish are the ideal model to re-examine metabolic responses to dietary disproportions of amino acids.

Do dietary amino acid profiles affect performance of larval gilthead seabream?

Received 8 January 2007; Accepted 6 June 2007 Abstract - Live preys commonly used in fish larval rearing seem to be imbalanced in terms of amino acids. Manipu- lation of their amino acid composition is difficult, but the use of microencapsulated diets allows this manipulation. This study analysed the effect of amino acid supplementation, in order to compensate for dietary amino acid imbalances, on growth and survival of gilthead seabream (Sparus aurata) larvae. Larvae were reared until 32 days after hatching, in a closed recirculating water system (19 ◦ C), using only live food (rotifers and Artemia). Thereafter, larvae were fed Artemia or one of the experimental microencapsulated diets: supplemented with indispensable amino acids (IAAsup diet), or supplemented with dispensable amino acids (DAAsup diet). Experiment lasted for 10 days. Dietary supple- mentation with indispensable amino acids resulted in A/E ratios ((each indispensable amino acid) × (total indispensable amino acids) −1 × 1000) more similar to the ones of larval seabream and in higher IAA:DAA ratios than in the DAA- sup diet. Survival was similar in larvae fed the IAAsup diet (75%) or Artemia (87%), but was significantly lower in larvae fed the DAAsup diet (52%). Larvae from all treatments more than doubled their average dry weight during the experimental period. Final dry weight was similar in larvae fed both microcapsules, but these were lighter than larvae fed with Artemia. Relative growth rate (RGR) and total biomass production tended to be higher in larvae fed the IAA- sup (RGR = 9% day −1 ) than the DAAsup diet (RGR = 7.5% day −1 ) and only in this last treatment these parameters were significantly lower than in larvae fed with Artemia. Therefore, dietary supplementation with indispensable amino acids resulted in a more balanced dietary amino acid profile, which significantly increased survival. Further studies introducing microdiets earlier in the development seem necessary in order to optimise growth.

Amino Acid Imbalance-Biochemical Mechanism and Nutritional Aspects

Amino acid imbalances refer to the deleterious effects that occur when a second-limiting amino acid or mixture of amino acid lacking a particular limiting amino acid is supplemented in diets marginal in one or more indispensable amino acids. In spite of variation in the conditions that have been used to induce amino acid imbalances, such as protein level in the diet, the extent of difference in total nitrogen content between basal and imbalanced diets, and kinds of amino acids used as imbalancing agents, the conspicuous common features of amino acid imbalances have been a decreased concentration of the limiting amino acid in blood, depression of feed intake and weight gain, and increased dietary content of the limiting amino acid needed to correct the imbalances. There is strong evidence that a decrease in the concentration of a limiting amino acid detected in the anterior prepyriform cortex of the brain is followed by behavioral effects, especially a decrease in feed intake. This might be due to the competition between the limiting amino acid and the amino acids in the imbalancing mixture for transport from blood into brain. One of the biochemical responses of animals fed amino acid imbalanced diets is a rapid decrease in the concentration of the limiting amino acid, which are due in part to an increase in catabolism of the limiting amino acid by the increased activities of enzymes involved in the catabolism of the amino acid. Practically, specific amino acid imbalances could be induced in swine and poultry diets that have been supplemented with lysine, methionine, tryptophan when threonine, isoleucine, valine, etc. are potentially third- or fourth-limiting in diets. In these cases supplementation of the limiting amino acid could be beneficial in preventing the decrease of feed intake that could otherwise occur as a result of amino acid imbalance.

Serotonin-3 receptors in gastric mechanisms of cholecystokinin-induced satiety

our understanding of the controls of food intake has increased substantially during the last 30 years. Important in this has been the recognition of the meal as a controlled, physiologically relevant unit of energy intake. During a meal, ingested nutrients accumulate in the stomach and gradually

WITHDRAWN: Ibotenic acid lesions of the anterior piriform cortex do not increase high-protein nor amino acid imbalanced diet intake in rats

The publisher regrets that this article is an accidental duplication of an article that has already been published, doi: 10.1016/j.appet.2006.03.001 . The duplicate article has therefore been withdrawn.

Ibotenic acid lesion of the anterior piriform cortex does not increase high‐protein diet intake in rats

INTRODUCTION High protein- or imbalanced amino acid diets are known to reduce food intake. The brain areas involved in this regulation are unknown. We hypothesized that the anterior piriform cortex (APC) plays this role. METHODS 34 male rats were included in either a control (n=8), sham (n=4) or a lesioned group (n=22). APC was lesioned bilaterally using ibotenic acid (6 μg) injected at one of two different sites: A-P 2.4 mm; L ± 4.0mm; D −6.5 mm (n=13) and A-P 3.0 mm; L ± 3.1 mm; D −6.3 mm (n=9) relative to bregma. Rats were then submitted to a P14 diet for at least 10 days, followed by a threonine devoid diet (Thr-Dev) for 5 days, then by a Thr-Dev corrected for threonine (Cor-diet) for 3 days and finally by a P55 diet for 3 days. Each period was preceded by 2 days of P14 diet in order to determine the basal level of energy intake. APC lesions were verified post-mortem using conventional histological methods. RESULTS Neither transition from P14 to Thr-Dev nor transition from P14 to Cor nor transition from P14 to P55 was altered by APC lesion. Moreover, relative to non-lesioned rats, APC lesioned rats did not increase food intake when given Thr-Dev or P55. Lesions were correctly placed. CONCLUSION The ibotenic acid sensitive neurons in the APC are not critical for the detection of high protein- or imbalanced amino acid diets.

Autonomic efferents affect intake of imbalanced amino acid diets by rats

An anorectic response occurs following ingestion of imbalanced amino acid (IMB) diets. There are three phases o this response: 1, recognition of the IMB diet; 2, conditioned development of an aversion to the IMB diet; and 3, adaptation. Blockade of peripheral serotonin-3 (5-HT 3) receptors or vagotomy attenuates Phase 2 of the anorectic response. We investigated whether sympathetic efferents interact with the ventral gastric branch (VGB), by cutting it (X), or with the 5-HT 3 receptor in these responses. First, VGBX and sham-operated (SHAM) groups were injected with vehicle or phenoxybenzamine (α-blocker), or nadolol (β-blocker) before introducing the IMB diet. At 3 h suppression of the IMB diet ingestion was unchanged, showing no sympathetic efferent effect on Phase 1. Intake of the IMB diet increased 12–24 h later only in the SHAM + phenoxybenzamine group, so the VGB was necessary for α-blockade to enhance IMB diet intake during Phase 2 or possibly Phase 3. On days 2–5, intakes by the SHAM + phenoxybenzamine, VGBX + phenoxybenzamine and VGBX + nadolol groups were elevated. Therefore, α-blockade enhanced adaptation alone, but VGBX was necessary for β-receptor blockade to augment Phase 3 adaptation. Both sympathetic efferents and the VGB are involved in Phases 2–3. Second, rats received vehicle or nadolol or scopolamine (nonselective muscarinic blocker) or pirenzepine (muscarinic M-1 receptor blocker), w+/− tropisetron (5-HT 3 blocker). Pirenzepine attenuated the tropisetron effect between 6–9 h, but then pirenzepine and nadolol enhanced the tropisetron effect between 9–12 h. Scopolamine attenuated the tropisetron effect between 9–12 h. While neither experiment showed effects during the recognition phase, the autonomic and serotonergic systems interact in the learned and adaptive responses to IMB diets.

Soy protein concentrate as a protein source for Senegalese sole (Solea senegalensisKaup 1858) diets: effects on growth and amino acid metabolism of postlarvae

The objective of this work was to evaluate the effect of a dietary amino acid imbalance, originating from the use of a soy protein concentrate (SPC) as the major protein source, on the growth performance and amino acid metabolism of Senegalese sole (Solea senegalensis) postlarvae. Senegalese sole (85.6±24.6 mg wet weight) were fed one of two experimental diets: one based on fish meal (FM) and another based on SPC. Diets were isonitrogenous (around 56% crude protein) and isoenergetic. Diet acceptability was very good and the growth rate was 6.9% day−1 for sole eating the FM diet and 6.0% day−1 for sole eating the SPC diet. Mass-specific ammonia excretion and the activities of selected amino acid metabolic enzymes (ALAT, ASAT and GDH) did not present significant differences between treatments, although this may have been due to the high variability found for these parameters in the SPC treatment. This variability may suggest different capacities of individual fish to adapt to the possible methionine dietary deficiency. The utilization of amino acids as a substrate for lipogenesis does not seem to be affected by the dietary protein source, since NAPDH-generating enzymes (G6PD and ME) had similar activities in both treatments. Amino acid metabolism in Senegalese sole postlarvae seems to be slightly affected by the dietary protein source. Nevertheless, the changes induced by the SPC diet do not seem to impair growth, at least at the high dietary protein level used in this experiment.

A balanced dietary amino acid profile improves amino acid retention in post-larval Senegalese sole ( Solea senegalensis)

The rearing of most marine fish larvae still relies on live food. Dietary amino acid (AA) imbalances when using live food in the larval rearing of flatfishes have been suggested. The aim of this study was to test if dietary AA supplementation affects AA metabolism in Senegalese sole ( Solea senegalensis) post-larvae. This was done by tube-feeding Artemia-fed sole with a dipeptide solution containing two potential limiting AA (leucine and phenylalanine), in order to supplement the larval gut content and to balance the dietary AA profile. Two experiments were done using different 14C-labelled AA as tracers. The first used a 14C-protein hydrolysate to test the effect of balancing the dietary AA profile on the overall AA metabolism. The second experiment analysed the effect of balancing the dietary AA profile on metabolism of three-selected AA: arginine, leucine and glutamate. A set-up to determine the handling of 14C-labelled AA was used, in order to quantify the absorption, catabolism and retention of the test mixtures by the sole post-larvae. The first experiment demonstrated that, when fish were fed the dipeptide supplement, AA catabolism decreased and AA retention increased. This agrees with the hypothesis that balancing the dietary AA profile increases AA retention in fish. In the second experiment, arginine and glutamate catabolism were reduced by the dipeptide supplementation. Leucine supplementation did not reduce leucine catabolism but instead increased arginine and glutamate retention. This result supports earlier studies that fish larvae are able to regulate their AA metabolism. A balanced dietary AA profile increases the AA retention and may improve growth and nitrogen utilisation.

Peptides that regulate food intake: somatostatin alters intake of amino acid-imbalanced diets and taste buds of tongue in rats.

The present studies were designed to evaluate a potential dose-dependent effect of somatostatin (SRIF) administered peripherally on intake of either a low-protein basal diet or threonine-imbalanced diet (THR-IMB), on body weight gain (DeltaBW), gut motility, and on the histology of taste buds in rats. SRIF administration had a dual effect related to its concentration, increasing the intake of THR-IMB diet at low concentration and decreasing THR-IMB diet at high concentration. During the light phase, SRIF treatment increased the intake of THR-IMB diet, suggesting that the usual anorectic effect induced by intake of THR-IMB diet was attenuated. High-dosage SRIF decreases gastrointestinal motility, which, in turn, can decrease food intake and DeltaBW. The combination of THR-IMB diet regimen and SRIF treatment also induced significant modifications on the taste buds of the tongue. The feeding response to an amino acid-imbalanced diet includes a learned aversion to the diet, and animals may use taste in establishing that aversion. Modifications of taste buds of SRIF-treated rats eating THR-IMB diet might explain the increase of imbalanced diet intake if treated rats perceive this food as less aversive.