Lysine Restriction Research Articles

RNA sequencing analysis revealed differentially expressed genes and their functional annotation in porcine longissimus dorsi muscle affected by dietary lysine restriction.

The objective of this study was to investigate the effects of dietary lysine restriction on the global gene expression profile of skeletal muscle in growing pigs. Twelve crossbred (Yorkshire × Landrace) barrows (initial BW 22.6 ± 2.04 kg) were randomly assigned to two dietary treatments (LDD: a lysine-deficient diet; LAD: a lysine-adequate diet) according to a completely randomized experiment design (n = 6). After feeding for 8 weeks, skeletal muscle was sampled from the longissimus dorsi of individual pigs. The muscle total RNA was isolated and cDNA libraries were prepared for RNA sequencing (RNA-Seq) analysis. The RNA-Seq data obtained was then analyzed using the CLC Genomics Workbench to identify differentially expressed genes (DEGs). A total of 80 genes (padj ≤ 0.05) were differentially expressed in the longissimus dorsi muscle of the pigs fed LDD vs. LAD, of which 46 genes were downregulated and 34 genes were upregulated. Gene Ontology (GO) analysis of the DEGs (padj ≤ 0.05) for functional annotation identified those GO terms that are mostly associated with the molecular functions of structural molecules and metabolic enzymes (e.g., oxidoreductase and endopeptidase), biological process of acute-phase response, and amino acid metabolism including synthesis and degradation in the extracellular matrix region. Collectively, the results of this study have provided some novel insight regarding the molecular mechanisms of muscle growth that are associated with dietary lysine supply.

215 Compensatory Growth Following One or Two Weeks of Lysine Restriction at Weaning

Abstract At weaning it is increasingly common to feed low crude protein (CP) and low standardized ileal digestible (SID) lysine (LYS) diets for improved health outcomes. This nutrient restriction often leads to decreased growth. Compensatory growth in this discussion is a period of enhanced growth that occurs after a period of nutrient restriction. This experiment was conducted to determine if compensatory growth occurs after one or two-weeks restriction of SID LYS at weaning. For the experiment, pigs (n = 252; ~23.5 days of age, 7.24 ± 1.02 kg BW, 8 reps/treatmentt, 5 or 6 pigs/pen) were randomly allotted to one of six treatments in a randomized complete block design with a 2 x 3 factorial arrangement of treatments. Treatment main effects were SID LYS/CP (0.07 or 0.065) or duration of SID LYS restriction (1.2% SID LYS for 0, 1, or 2 weeks). When not restricted, pigs were fed a diet with 1.5% SID LYS. After the first 14 days, all pigs consumed a common diet for 24 days with 1.35% SID LYS. Body weight, feed disappearance, visual fecal scores, and visual piglet scores were measured. Visual fecal scores (1 = normal to 4 = watery) and visual pig appearance scores (1 = pale and hairy to 4 = normal color and well-rounded muscle) were assessed on ordered likert scales to determine the probabilities of observing a more normal stool quality and a worse visual appearance, respectively. Performance data were analyzed as a general linear model. Stool quality and visual appearance were analyzed as a generalized linear mixed model. Pairwise comparisons with Tukey adjustment were used for treatment LSmean separation. No effect of SID LYS/CP or interaction of SID LYS/CP and SID LYS program was detected. Results for the main effect of SID LYS program is presented in Table 1. Restricting SID LYS for the first week resulted in decreased ADG and gain:feed (P < 0.05; Table 1). This same effect was observed in week 2. However, those pigs that moved from 1.2% SID LYS in week 1 to 1.5% SID LYS in week 2 had the similar ADG and gain:feed during week 2 as the pigs that consumed 1.5% SID LYS for both weeks. Pigs that had two weeks of SID LYS restriction had lower body weight at d 38 (P< 0.05), whereas pigs with one week of SID LYS restriction had similar body weight at d 38 to unrestricted LYS fed pigs. In addition to performance, unrestricted LYS decreased stool quality (P<0.05) but improved the visual appearance of pigs (P < 0.10) at d 14 and d 38. In conclusion, pigs can have compensatory growth when SID LYS is restricted from 1.5% to 1.2% for one week, but not two weeks.

Effect of phased reduction of dietary digestible lysine density on growth performance, thigh meat, and biomechanical characteristics of tibia in broiler chickens.

In this study, growth performance, nutrient intake, thigh meat quality, fatty acid composition of thigh meat, and biomechanical characteristics of tibia of broiler chickens in response to phased restriction of dietary digestible lysine (dLys) were evaluated. A total of 180 male broiler chickens distributed to 3 experimental groups were fed control diets, 85% dLys diet in grower phase (GRO 85% dLys), or 85% dLys diets in grower and finisher phases (GRO-FIN 85% dLys). Feeding 85% dLys suppressed the feed intake that suppressed the growth performance, slaughter weight, and thigh weight of broiler chickens compared to control group (P < 0.05). Average daily dLys, Ca, and P intakes were suppressed in groups fed 85% dLys diets in comparison with control group (P < 0.05) due to the suppression of feed intake. While most fatty acid concentrations in thigh meat were not different among the groups, eicosanoic acid (C20:0) in thigh meat was greater in GRO-FIN 85% dLys group than control group (P = 0.002). Antioxidant status of thigh meat of broiler chickens was not affected by the phased restriction of dietary dLys compared to control group. Bone breaking strength and ultimate strength were greater in control group than 85% dLys groups (P < 0.05). In conclusion, phased dilution of dietary dLys to 85% of the required allowance yields weaker legs and tibia bones by suppressing the Ca and P intakes as a function of reduced feed intake in broiler chickens.

Lysine catabolism reprograms tumour immunity through histone crotonylation.

Cancer cells rewire metabolism to favour the generation of specialized metabolites that support tumour growth and reshape the tumour microenvironment1,2. Lysine functions as a biosynthetic molecule, energy source and antioxidant3-5, but little is known about its pathological role in cancer. Here we show that glioblastoma stem cells (GSCs) reprogram lysine catabolism through the upregulation of lysine transporter SLC7A2 and crotonyl-coenzyme A (crotonyl-CoA)-producing enzyme glutaryl-CoA dehydrogenase (GCDH) with downregulation of the crotonyl-CoA hydratase enoyl-CoA hydratase short chain 1 (ECHS1), leading to accumulation of intracellular crotonyl-CoA and histone H4 lysine crotonylation. A reduction in histone lysine crotonylation by either genetic manipulation or lysine restriction impaired tumour growth. In the nucleus, GCDH interacts with the crotonyltransferase CBP to promote histone lysine crotonylation. Loss of histone lysine crotonylation promotes immunogenic cytosolic double-stranded RNA (dsRNA) and dsDNA generation through enhanced H3K27ac, which stimulates the RNA sensor MDA5 and DNA sensor cyclic GMP-AMP synthase (cGAS) to boost type I interferon signalling, leading to compromised GSC tumorigenic potential and elevated CD8+ T cell infiltration. A lysine-restricted diet synergized with MYC inhibition or anti-PD-1 therapy to slow tumour growth. Collectively, GSCs co-opt lysine uptake and degradation to shunt the production of crotonyl-CoA, remodelling the chromatin landscape to evade interferon-induced intrinsic effects on GSC maintenance and extrinsic effects on immune response.

Metabolomics analysis of antiquitin deficiency in cultured human cells and plasma: Relevance to pyridoxine-dependent epilepsy.

Deficiency of antiquitin (α-aminoadipic semialdehyde dehydrogenase), an enzyme involved in lysine degradation and encoded by ALDH7A1, is the major cause of vitamin B6 -dependent epilepsy (PDE-ALDH7A1). Despite seizure control with high dose pyridoxine (PN), developmental delay still occurs in approximately 70% of patients. We aimed to investigate metabolic perturbations due to possible previously unidentified roles of antiquitin, which may contribute to developmental delay, as well as metabolic effects of high dose pyridoxine supplementation reflecting the high doses used for seizure control in patients with PDE-ALDH7A1. Untargeted metabolomics by high resolution mass spectrometry (HRMS) was used to analyze plasma of patients with PDE-ALDH7A1 and two independently generated lines of cultured ReNcell CX human neuronal progenitor cells (NPCs) with CRISPR/Cas mediated antiquitin deficiency. Accumulation of lysine pathway metabolites in antiquitin-deficient NPCs and western-blot analysis confirmed knockdown of ALDH7A1. Metabolomics analysis of antiquitin-deficient NPCs in conditions of lysine restriction and PN supplementation identified changes in metabolites related to the transmethylation and transsulfuration pathways and osmolytes, indicating a possible unrecognized role of antiquitin outside the lysine degradation pathway. Analysis of plasma samples of PN treated patients with PDE-ALDH7A1 and antiquitin-deficient NPCs cultured in conditions comparable to the patient plasma samples demonstrated perturbation of metabolites of the gamma-glutamyl cycle, suggesting potential oxidative stress-related effects in PN-treated patients with PDE-ALDH7A1. We postulate that a model of human NPCs with CRISPR/Cas mediated antiquitin deficiency is well suited to characterize previously unreported roles of antiquitin, relevant to this most prevalent form of pyridoxine-dependent epilepsy.

Dietary lysine level affects digestive enzyme, amino acid transport and hepatic intermediary metabolism in turbot (Scophthalmus maximus)

Lysine is one of the most important essential amino acids in fish, especially in the feed formulated with high levels of plant ingredients. Lysine restriction always led to growth inhibition and poor feed utilization. However, little information was available on its effects on digestion, absorption, and metabolism response in fish. In the present study, three experimental diets were formulated with three lysine levels, 1.69% (LL group), 3.32% (ML group), and 4.90% (HL group). A 10-week feeding trial was carried out to explore the effects of dietary lysine levels on the digestive enzymes, amino acid transporters, and hepatic intermediary metabolism in turbot (Scophthalmus maximus). As the results showed, the activities of lipase and trypsin in ML group were higher than in other groups. Lysine restriction inhibited the expression levels of peptides and amino acid transporters such as PpeT1, y+LAT2, b0,+AT, and rBAT but significantly induced the expression of CAT1. Meanwhile, lysine deficiency elevated the content of T-CHO and LDL-C in plasma, while a higher HDL-C/LDL-C ratio was observed in ML group. For hepatic intermediary metabolism, the increase of lysine level induced the mRNA expression of G6Pase1 and FBPase, but no differences were observed in the expression of the key regulators in glycolysis pathway, such as GK and PK. Furthermore, an appropriate increase in the level of lysine promoted the genes involved in lipolysis, including PPARα, ACOX1, CPT1A, and LPL. However, no differences were observed in the expression of PPARγ, FAS, SREBP1, and LXR, which were important genes related to lipid synthesis. These results provide clues on the metabolic responses on dietary lysine in teleost.

Redução temporária de lisina digestível em dietas de leitões em fase de creche: desempenho e viabilidade econômica

ABSTRACT To evaluate the effects of temporary dietary lysine restriction on nursery pigs’ growth performance and its economic viability compared to control diets, 144 piglets (21-d-old) were assigned to randomized blocks, with two treatments and twelve replicates. The treatments were control-lys: lysine level as recommended from 21-32 and 32-42 days and low-lys: 90% of the lysine level of the control-lys diets. From 42 to 62 days, all animals received a control diet. From 21 to 32 days, pigs fed low-lys had worse average daily gain (ADG), feed conversion, and 32-d body weight (BW; P ≤ 0.05). From 32 to 42 days, pigs fed low-lys had lower average daily feed intake, ADG, and 42-d BW (P ≤ 0.05). From 42 to 62 days, pigs had similar performance (P &gt; 0.05). Overall (21 to 62 days), pigs fed the low-lys had lower (P &lt;0.05) ADG and final BW. At 27 and 29 days, pigs fed the low-lys diet had a higher (P≤0.05) incidence of diarrhea. The lowest feed cost and the highest economic efficiency index were recorded for the low-lys treatment. However, pigs fed the control-lys presented a 3.9% higher profitability. In conclusion, a temporary reduction of lysine in the diets of nursery pigs followed by an unrestricted diet in the subsequent period led to worse growth performance and lower economic viability.

Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures.

Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). ATQ is one of the enzymes involved in lysine oxidation; thus, its deficiency leads to the accumulation of toxic metabolites in body fluids. PDE is characterized by persistent, recurrent neonatal seizures that cannot be well controlled by antiepileptic drugs but are responsive clinically and electrographically to daily pyridoxine (vitamin B6) supplementation. Although the phenotypic spectrum distinguishes between typical and atypical, pyridoxine-dependent is true for each. Diagnosis may pose a challenge mainly due to the rarity of the disorder and the fact that seizures may not occur until childhood or even late adolescence. Moreover, patients may not demonstrate an obvious clinical or electroencephalography response to the initial dose of pyridoxine. Effective treatment requires lifelong pharmacologic supplements of pyridoxine, and dietary lysine restriction and arginine enrichment should improve prognosis and avoid developmental delay and intellectual disability. The purpose of this review is to summarize briefly the latest reports on the etiology, clinical symptoms, diagnosis, and management of patients suffering from pyridoxine-dependent epilepsy.

Dietary lysine restriction induces lipid accumulation in skeletal muscle through an increase in serum threonine levels in rats

We previously reported that dietary amino acid restriction induces the accumulation of triglycerides (TAG) in the liver of growing rats. However, differences in TAG accumulation in individual cell types or other tissues were not examined. In this study, we show that TAG also accumulates in the muscle and adipose tissues of rats fed a low amino acid (low-AA) diet. In addition, dietary lysine restriction (low-Lys) induces lipid accumulation in muscle and adipose tissues. In adjusting the nitrogen content to that of the control diet, we found that glutamic acid supplementation to the low-AA diet blocked lipid accumulation, but supplementation with the low-Lys diet did not, suggesting that a shortage of nitrogen caused lipids to accumulate in the skeletal muscle in the rats fed a low-AA diet. Serum amino acid measurement revealed that, in rats fed a low-Lys diet, serum lysine levels were decreased, while serum threonine levels were significantly increased compared with the control rats. When the threonine content was restricted in the low-Lys diet, TAG accumulation induced by the low-Lys diet was completely abolished in skeletal muscle. Moreover, in L6 myotubes cultured in medium containing high threonine and low lysine, fatty acid uptake was enhanced compared with that in cells cultured in control medium. These findings suggest that the increased serum threonine in rats fed a low-Lys diet resulted in lipid incorporation into skeletal muscle, leading to the formation of fatty muscle tissue. Collectively, we propose conceptual hypothesis that “amino-acid signal” based on lysine and threonine regulates lipid metabolism.

Lysine and Threonine Restriction Reproduced the Lower Synthesis but Not the Higher Catabolism of Liver and Muscle Protein of Severely Protein Restricted Growing Rats

Abstract Objectives The availability of indispensable amino acids (IAA) modulates protein turnover. More particularly AAI deficiency reduces protein synthesis while the consequence on proteolysis remains unclear. The present study aims to evaluate the specific response of both protein synthesis and proteolysis to a diet restricted on one strictly indispensable IAA, either lysine or threonine Methods Sixty-four growing rats were divided into 8 groups (n = 8/group). They were fed for 3 weeks isocaloric diets composed with different levels of lysine or threonine (L or T), 15, 25, 40, 60, 75, 100 or 170% of the theoretical lysine/threonine requirements. At the end of the experiment, rats were injected with valine13C and tissues and biological fluids were collected for gene expression measurement and blood amino acids (AA). Protein synthesis rate (Fractional and Absolute rate synthesis, ie FSR, ASR) were determined in liver and muscle. Statistical analysis was done by 1- or 2-factor ANOVA, when data were repeated. Results Severe (L/T15, L/T25) and moderate (T40) lysine or threonine deficiency resulted in a decrease in body weight gain due to a decrease in lean body mass. Severe restriction (L15, T15, T25) decreased the muscle FSR whereas no effect was observed in the liver. When the rate of protein synthesis was expressed per tissue, the ASR was decreased by severe restriction of lysine and threonine in liver and muscle and by moderate threonine deficiency (T40, T60, T75) in muscle. In liver, no effect of lysine and threonine on proteolysis was observed. In muscle, only severe lysine (L15) deficiency increased proteolysis. Dietary lysine deficiency induced a decrease in lysine concentration in the portal vein and in the vena cava whereas for threonine deficiency, all AAIs except threonine were decreased in the portal vein and vena cava. Conclusions These results indicate that the decreased protein synthesis is the primary mechanism involved in decreased lean body mass in response to the severe deficiency in a single AAI. Deficiency of a single AAI reproduce the effect of the low protein diet on protein synthesis. Lysine and threonine deficiency differently affect for a part protein turnover probably in relation with the tissue where they are metabolized. Funding Sources This study was funded by the doctoral school ABIES and AlimH-INRAE department.

Lysine Depletion during Different Feeding Phases: Effects on Growth Performances and Meat Quality of Broiler Chickens.

Simple SummaryIn the past, many studies have been carried out to investigate the effect of lysine supplementation on broilers’ growth performances and feed efficiency. However, the knowledge concerning the reduction of the dietary content of this essential amino acid is limited and mainly restricted to the production performances of the birds. Within this context, the present study aimed at assessing the impact of lysine restriction during grower I (10–20 d) and grower I and II (10–20 and 21–34 d) feeding phases on live performances, breast meat quality traits and technological properties, as well as on the incidence and severity of abnormalities affecting the pectoral muscles (i.e., white striping, wooden breast and spaghetti meat). Lysine restriction during different feeding phases exerts negligible effects on the production performances of the broilers due to their compensatory growth. In addition, the increased anserine content following lysine depletion might have exerted a protective role against protein denaturation by buffering the acidic end-products generated during post-mortem rigor development.The present study aimed at assessing the impact of lysine restriction performed during different feeding phases on growth performances, meat quality traits and technological properties as well as on the incidence and severity of breast muscle abnormalities. For this purpose, a total of 945 one-day-old Ross 308 male chicks was randomly divided into three experimental groups: CONT, fed a four feeding phases commercial diet, GRW I, and GRW I + II fed CONT diet with the depletion of synthetic lysine during grower I and grower I and II feeding phases, respectively. Productive performances were recorded throughout the whole rearing cycle and the incidence of breast muscle growth-related abnormalities assessed at slaughter (49 d) on 280 breasts/group. Quality traits and technological properties of breast meat were measured on a total of 54 Pectoralis major muscles. Lysine restriction only marginally affected the productive performances and the quality parameters of breast meat. The increased (p < 0.05) solubility of the protein fraction along with the remarkably higher (p < 0.05) anserine content found in GRW I + II suggests an increased energy requirement in the pectoral muscles belonging to lysine-restricted birds and supports the hypothesis of a reduced protein synthesis taking place within these muscles.

ALDH7A1 Gene and Its Related Pyridoxine-Dependent Epilepsy

AbstractDespite being classically reported as caused by mutations in solute carriers genes (SLC2A1), it has been recently shown that also mutations in ALDH7A1 can cause pyridoxine-dependent epilepsy (PDE). ALDH7A1 is a gene encoding for the antiquitin, an enzyme that catalyzes the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-α-aminoadipic semialdehyde/L-Δ1-piperideine 6-carboxylate. It is a highly treatable disorder, but nevertheless it is still not certain when to consider this diagnosis and how to test for it. It is possible to identify a classical form and an atypical one of PDE associated with more than 70 mutations of ALDH7A1 gene. The typical form is characterized by the onset of seizures within the first month of life and can be treated with pyridoxine in monotherapy, as they are not responsive to traditional anticonvulsant therapy. The atypical forms are equally pyridoxine-dependent, but are characterized by a later onset of seizures, sometimes up to the age of 3 years. Several brain abnormalities have been associated with ALDH7A1 mutations. Seizure control is achieved by the administration of high-dose pyridoxine, which must be started in the patient as soon as possible. However, it has been observed that pyridoxine therapy does not prevent developmental delay in most cases; in these cases, it can be recommended and useful to supplement arginine with pyridoxine therapy associated with a dietary restriction of lysine.

PSVI-15 Effects of Dietary SID Lysine Restriction in the Growing Period and Number of Dietary Phases on Growth Performance of Growing-finishing Pigs

Abstract This study evaluated the effects of dietary SID lysine restriction in the growing period and number of dietary phases in the growing-finishing (GF) period on growth performance of GF pigs (32.7 ± 9.43 kg to 115.5 ± 8.18 kg BW). A RCBD (block = gender and start day) was used with a 3 × 2 factorial arrangement of treatments: 1) Dietary SID Lysine Level {Control [NRC (2012) recommendation]; Moderate Restriction [0.15% lower than Control]; Aggressive Restriction [0.30% lower than Control]} and 2) Number of Dietary Phases in GF (4 vs. 2). Lysine level treatments were applied from 32 to 64 kg BW. Diets were based on corn-soybean meal and corn coproducts, formulated to be isocaloric, and to meet or exceed recommendations of NRC (2012) for each phase, with the exception of SID lysine levels which were according to treatment. A total of 4,488 pigs were housed in single-sex groups of 34 pigs (22 replicates) with floor space of 0.63 m2/ pig. Pigs had ad libitum access to feed and water throughout and were weighed at start and end of the study; feeder additions were recorded. Pen was the experimental unit and data were analyzed using R version 3.6.2. The model accounted for the fixed effect of treatments, the interaction, and random effect of block. There were no treatment interactions (P &amp;gt; 0.05) and no effect (P &amp;gt; 0.05) of Number of Dietary Phases on overall growth performance. Decreasing dietary SID lysine linearly reduced (P &amp;lt; 0.05) overall ADG and ADFI with no effect (P &amp;gt; 0.05) on G:F. Restricting dietary SID lysine level to the extent used in this study reduced overall growth rate with no impact on feed efficiency.

Evaluation of nutritional strategies to slow growth rate then induce compensatory growth in 90-kg finishing pigs.

Two 44-d experiments were conducted to evaluate nutritional strategies with different concentrations of dietary lysine (and other amino acids) on growth rate and subsequent compensatory gain of 90-kg finishing pigs. Three diets were formulated to contain 0.70 (control), 0.50% and 0.18% standardized ileal digestible (SID) Lys. In Exp. 1, 356 pigs (Line 241 × 600, DNA; initially 89.0 ± 1.10 kg) were used with four treatments. From d 0 to 28, pigs received either the control or the 0.50%-Lys diet. On d 28, pigs either remained on these diets or were switched the 0.18%-Lys diet until d 44. There were 18 pens per treatment from d 0 to 28 and 9 pens per treatment from d 28 to 44. From d 0 to 28, pigs fed the 0.50%-Lys diet had decreased (P < 0.001) ADG and G:F compared to those fed the control diet. From d 28 to 44, pigs switched to the 0.18%-Lys diet had decreased (P < 0.05) ADG and G:F compared to pigs that remained on the control or 0.50%-Lys diets. From d 0 to 44, pigs fed 0.50%-Lys diet for 44-d had decreased (P < 0.05) ADG, G:F, and percentage carcass lean compared to pigs fed the control diet. Pigs fed the 0.50%-Lys diet then the 0.18%-Lys diet had decreased (P < 0.05) ADG and G:F compared to other treatments. Pigs fed the 0.50%-Lys diet for 44-d and pigs fed the control diet then 0.18%-Lys diet had decreased (P < 0.05) ADG, G:F, and percentage carcass lean compared to control pigs. In Exp. 2, 346 pigs (Line 241 × 600, DNA; initially 88.6 ± 1.05 kg) were used to evaluate compensatory growth after varying durations of dietary lysine restriction. A total of four treatments were used including pigs fed the control diet for 44-d or fed the 0.18%-Lys diet for 14, 21, or 28-d and then fed the control diet until the conclusion of the experiment on d 44. There were nine pens per treatment. On average, pigs fed the 0.18%-Lys diet grew 49% slower than the control. Compared to the control, ADG of pigs previously fed the 0.18%-Lys diet increased (P < 0.05) 28% during the first week after switching to the control diet and 12% for the rest of the trial. Despite this improvement, overall ADG, G;F, final BW, and percentage carcass lean decreased (linear, P < 0.05) as the duration of Lys restriction increased. In summary, feeding Lys-restricted diets reduced the ADG and G:F of finishing pigs. Compensatory growth can be induced in Lys-restricted finishing pigs, but the duration of restriction and recovery influences the magnitude of compensatory growth.

Dietary Lysine Regulates Body Growth Performance via the Nutrient-Sensing Signaling Pathways in Largemouth Bass (Micropterus salmoides)

Lysine is known to be a functional nutrient from yeast to human beings. However, the mechanisms for lysine to regulate body growth and metabolism in fish species are far from fully illuminated. In order to elucidate the molecular effects of lysine on growth performance and metabolism, largemouth bass (Micropterus salmoides), which is extremely sensitive to protein composition, was chosen as the experimental model. Juvenile largemouth bass (4.16 ± 0.02g) were fed with the lysine control diet (LC diet), the lysine supplementation diet (LS diet), and the low lysine diet (LL diet) for 8 weeks. The results showed that the LS diet group significantly increased fish growth, feed efficiency, and nutrient retention compared with those of the LL diet group in largemouth bass. Moreover, compared to the LL diet, lysine supplementation also elevated the plasma total protein, total EAA, total AA, and some individual AA concentrations. Mechanistically, lysine supplementation had a significant effect to decrease the mRNA expression levels of peptide and AA transporters induced by lysine restriction. Lysine supplementation also had an important impact on regulating the target of rapamycin (TOR) signaling pathway. More importantly, the key regulators in the amino acid response (AAR) signaling pathway were also down-regulated by lysine supplementation. Our results provide a clear elucidation of how dietary lysine affected growth performance, physiological and biochemical responses, and signaling responses and represent a sound foundation for using lysine to improve the nutrient utilization of poultry by-product meal in largemouth bass.

76 Compensatory growth following lysine restriction in grow-finish pigs: literature review and analysis

Abstract A literature review on compensatory growth induced by lysine restriction in grow-finish pigs was conducted. First, a database was developed to standardize comparisons across the peer-reviewed literature and characterize the occurrence of compensatory growth. Publications had to include: pigs with minimum initial weight of 15 kg; a group of “non-restricted pigs” not subjected to a restriction period; a group of “restricted pigs” subjected to a restriction period induced by decreasing lysine alone, lysine and other amino acids, or crude protein in diets; a recovery period following the restriction period in which the same diet was fed to restricted and non-restricted pigs; and ad libitum feed consumption. The database included 14 publications and 57 comparisons expressed as relative differences between restricted pigs and non-restricted pigs. The database analysis categorized compensatory growth into complete, incomplete, and no compensatory growth, and characterized the patterns of restriction and recovery in each category (Table 1). The data analysis supports that compensatory growth induced by lysine restriction in grow-finish pigs occurs. The degree of lysine restriction as well as restriction and recovery duration seem critical in explaining differences between complete and incomplete compensatory growth. Also, inadequate lysine level in the recovery period seems to be associated with incomplete or no compensatory growth. Compensatory growth is more likely if: degree of lysine restriction is between 10 to 30%; lysine restriction is induced before pigs reach their maximum protein deposition; duration of lysine restriction is short and duration of recovery period is long; and lysine level in the recovery period is close to or above the estimated requirements.

Inconsistencies in the Nutrition Management of Glutaric Aciduria Type 1: An International Survey.

Glutaric aciduria type 1 (GA-1) is a cerebral organic aciduria characterized by striatal injury and progressive movement disorder. Nutrition management shifted from a general restriction of intact protein to targeted restriction of lysine and tryptophan. Recent guidelines advocate for a low-lysine diet using lysine-free, tryptophan-reduced medical foods. GA-1 guideline recommendations for dietary management of patients over the age of six are unclear, ranging from avoiding excessive intake of intact protein to counting milligrams of lysine intake. A 22–question survey on the nutrition management of GA-1 was developed with the goal of understanding approaches to diet management for patients identified by newborn screening under age six years compared to management after diet liberalization, as well as to gain insight into how clinicians define diet liberalization. Seventy-six responses (25% of possible responses) to the survey were received. Nutrition management with GA-1 is divergent among surveyed clinicians. There was congruency among survey responses to the guidelines, but there is still uncertainty about how to counsel patients on diet optimization and when diet liberalization should occur. Ongoing clinical research and better understanding of the natural history of this disease will help establish stronger recommendations from which clinicians can best counsel families.

Temporary lysine restriction in newly weaned pigs does not affect carcass and loin quality at slaughter

Two hundred and forty weaned pigs [initial body weight (BW) 7.2 ± 0.07 kg] were allocated to three diets (eight pens per treatment, 10 pigs per pen) to determine the effects of a temporary lysine (Lys) restriction on subsequent growth, body composition, as well as carcass and loin quality at slaughter. For a 3 wk restriction period, pigs were fed diets that were 110% (control), 20% (Lys20), or 40% (Lys40) below estimated Lys requirements. Thereafter, all pigs were fed a common grower diet containing 120% of the estimated Lys requirement for 6 wk (recovery period) and commercial diets until slaughter at ∼125 kg BW. During the restriction period, average daily gain, gain-to-feed ratio, and whole body protein deposition decreased (linear; P &lt; 0.01), while whole body lipid deposition increased (linear; P &lt; 0.001) with decreased dietary Lys concentrations. At the end of the recovery period, there were no differences in BW, although whole body protein concentration tended to decrease and lipid concentration tended to increase (linear; P = 0.07 and 0.06, respectively) with decreased dietary Lys concentrations. At ∼125 kg, there were no differences in BW, chemical composition, or carcass and loin quality. Compensatory growth was achieved by ∼125 kg BW after a 3 wk Lys restriction for newly weaned pigs without negatively impacting carcass and loin quality.

A review of compensatory growth following lysine restriction in grow-finish pigs1

Compensatory growth induced by lysine (Lys) restriction in grow-finish pigs is a complex physiological process affected by many factors and interactions, principally genotype, stage of growth at restriction, nature of nutritional restriction, and patterns of restriction and recovery. The scarcity of standard comparisons across the literature has hindered the characterization of important determinants of compensatory growth. Therefore, the present publication aims to review the current state of knowledge on compensatory growth induced by Lys restriction in grow-finish pigs, develop a database from peer-reviewed literature to standardize comparisons to characterize the occurrence of compensatory growth, and provide practical considerations for compensatory growth under field conditions. The literature search focused on publications directly or indirectly evaluating compensatory growth by having a period of Lys restriction followed by a recovery period of Lys sufficiency for grow-finish pigs. The database included 14 publications and 57 comparisons expressed as relative differences of restricted pigs compared to nonrestricted pigs. The database analysis described compensatory growth into complete, incomplete, and no compensatory growth categories and characterized the patterns of restriction and recovery in each category. The review of literature and database analysis supports the occurrence of compensatory growth induced by Lys restriction in grow-finish pigs. The degree of Lys restriction and duration of restriction and recovery periods seem to be critical in explaining differences between complete and incomplete compensatory growth, whereas Lys level in the recovery period seems to be critical between incomplete or no compensatory growth. Compensatory growth seems to be more likely if: 1) the degree of Lys restriction is between 10% and 30%; 2) Lys restriction is induced before pigs reach their maximum protein deposition; 3) duration of Lys restriction is short (maximum 40–45% overall duration) and duration of recovery period is long (minimum 55–60% overall duration); and 4) Lys level in recovery is close to or above the estimated requirements. In addition, compensatory growth can occur under commercial conditions and there seems to be an opportunity to exploit compensatory growth in grow-finish pigs to reduce feed cost and improve feed efficiency under certain market conditions.

Dietary lysine affects amino acid metabolism and growth performance, which may not involve the GH/IGF-1 axis, in young growing pigs1.

Lysine is the first limiting amino acid (AA) in typical swine diets. Our previous research showed that dietary lysine restriction compromised the growth performance of late-stage finishing pigs, which was associated with the changes in plasma concentrations of nutrient metabolites and hormone insulin-like growth factor 1 (IGF-1). This study was conducted to investigate how dietary lysine restriction affects the plasma concentrations of selected metabolites and three anabolic hormones in growing pigs. Twelve individually penned young barrows (Yorkshire × Landrace; 22.6 ± 2.04 kg) were randomly assigned to two dietary treatments (n = 6). Two corn and soybean meal based diets were formulated to contain 0.65% and 0.98% standardized ileal digestible lysine as a lysine-deficient (LDD) and a lysine-adequate (LAD) diets, respectively. During the 8-week feeding trial, pigs had ad libitum access to water and their respective diets, and the growth performance parameters including average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were determined. At the end of the trial, jugular vein blood was collected for plasma preparation. The plasma concentrations of free AA and six metabolites were analyzed with the established chemical methods, and the hormone concentrations were analyzed with the commercial ELISA kits. Data were analyzed with Student's t-test. The ADG of LDD pigs was lower (P < 0.01) than that of LAD pigs, and so was the G:F (P < 0.05) since there was no difference in the ADFI between the two groups of pigs. In terms of free AA, the plasma concentrations of lysine, methionine, leucine, and tyrosine were lower (P < 0.05), while that of β-alanine was higher (P < 0.01), in the LDD pigs. The total plasma protein concentration was lower (P < 0.02) in the LDD pigs, whereas no differences were observed for the other metabolites between the two groups. No differences were observed in the plasma concentrations of growth hormone (GF), insulin, and IGF-1 between the two groups as well. These results indicate that the lack of lysine as a protein building block must be the primary reason for a reduced body protein synthesis and, consequently, the compromised G:F ratio and ADG. The changes in the plasma concentrations of total protein and four AA suggest that the compromised growth performance might be associated with some cell signaling and metabolic pathways that may not involve the GH/IGF-1 axis.