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

Symbiotic bacteria support host growth upon malnutrition. How bacteria achieve this remains partly elusive. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate such mechanisms. Using chemically-defined holidic diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets. We show that in this context Lp supports its host's growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophila's enterocytes. Our data indicate that Lp's r/tRNAs loci products activate GCN2 in a subset of larval enterocytes, a mechanism necessary for the host's adaptation to amino acid imbalance that ultimately supports growth. Our findings unravel a novel beneficial molecular dialog between hosts and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.

224 Amino Acid Imbalance with Excess Methionine in Late-finishing Pigs: Effects on Performance and Carcass Quality

Limitations in harvest facility capacity can necessitate feeding programs to slow growth rate in late-finishing pigs. In Trial 1, six dietary regimens were used with 423 pigs (initial weight, 109 kg) randomly allotted in a 35 d study. The regimens consisted of: 1) Con (11.7% CP diet), 2) Low Protein (LP 8.8% CP), 3) Methionine (Met) 1% (LP plus 1% added Met for 35 d), 4) Met 1–1.8% (LP plus 1, 1.2, 1.4, 1.6 and 1.8% added Met for d 0–7, 7–14, 14–21, 21–28 and 28–35 d, respectively), 5) Met 2% (LP plus 2% added Met for 35 d) and 6) Met 1.5–2.3% (LP plus 1.5, 1.7, 1.9, 2.1 and 2.3%, added Met for d 0–7, 7–14, 14–21, 21–28 and 28–35 d, respectively). Pigs on Met 1% had reduced overall ADG and ADFI (P < 0.05) with similar G:F vs. pigs on LP. Compared to pigs on Met 1%, pigs on Met 1–1.8%, Met 2%, and Met 1.5–2.3% had reduced (P < 0.05) ADG of 28, 54 and 53%, respectively; and decreased (P < 0.05) ADFI of 12, 26 and 26%, respectively. In Trial 2, three regimens were used with 393 pigs (initial weight, 109 kg) in a 35 d study. The regimens consisted of 1) Met 2%, 2) Met 1.5–2.3% and 3) Met 2.0–2.8% (LP plus 2.0, 2.2, 2.4, 2.6 and 2.8% added Met for d 0–7, 7–14, 14–21, 21–28 and 28–35 d, respectively). Regimens 1 and 2 were identical to Trial 1. Overall, pigs on Met 1.5–2.3% had ADG and ADFI which were greater (P < 0.001) compared to pigs on Met 2%. Pigs on Met 2–2.8% had an overall ADG and ADFI which were less (P < 0.05) than those pigs on Met 2%. These data suggest that growth can be manipulated with excess Met.

Amino acid imbalance with excess methionine in late-finishing pigs: effects on performance and carcass quality

Limitations in harvest facility capacity can necessitate feeding strategies to slow growth rate in late-finishing pigs. In Exp. 1, six dietary treatments were used with 423 late-finishing pigs (initial weight of 109.5 kg) randomly allotted (mixed-sex) across 24 pens in a 35 d study. The treatments consisted of: 1) Positive Control (PC, 11.7% CP (Crude Protein) diet with added amino acids (AA), 2) Methionine (Met) 0% (8.8% CP with added AA), 3) Met 1% (8.8% CP with added AA plus 1% added Met for 35 d), 4) Met 1-1.8% (8.8% CP with added AA plus 1, 1.2, 1.4, 1.6 and 1.8% added Met for d 0-7, 7-14, 14-21, 21-28 and 28-35 d, respectively), 5) Met 2% (8.8% CP with added AA plus 2% added Met for 35 d) and 6) Met 1.5-2.3% (8.8% CP with added AA plus 1.5, 1.7, 1.9, 2.1 and 2.3% added Met for d 0-7, 7-14, 14-21, 21-28 and 28-35 d, respectively). Overall, pigs on the PC had improved ADG and G:F (P < 0.05) compared to the other five treatments. Pigs on Met 1% had reduced overall ADG and ADFI (P < 0.05) with similar G:F compared to pigs on Met 0%. Compared to pigs on Met 1%, pigs on Met 1-1.8%, Met 2%, and Met 1.5-2.3% had reduced (P < 0.05) ADG of 28, 54 and 53%, respectively; and decreased (P < 0.05) ADFI of 12, 26 and 26%, respectively. Dressing percent was similar among all six treatments. In Exp. 2, three dietary treatments were used with 393 late-finishing pigs (average initial weight was 108.8 kg) randomly allotted (mixed-sex) across 24 pens in a 35-d study. The treatments consisted of 1) Met 2%, 2) Met 1.5-2.3% and 3) Met 2.0-2.8% (8.8% CP with added AA plus 2.0, 2.2, 2.4, 2.6 and 2.8% added Met for d 0-7, 7-14, 14-21, 21-28 and 28-35 d, respectively). Treatments 1 and 2 were identical to Exp. 1. Overall, pigs on Met 1.5-2.3% had ADG of 241 g and ADFI of 2,040 g which were greater (P < 0.001) compared to pigs on Met 2% with ADG of 57 g and ADFI of 1,515 g. Furthermore, pigs on Met 2-2.8% had an overall ADG of -62 g and ADFI of 1,254 g which were less (P < 0.05) than those pigs on Met 2%. Percent lean and dressing percent were similar among the three treatments. These data suggest that late-finishing growth can be manipulated in a concise and effective manner by creating amino acid imbalances with varying levels of excess Met.

Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina

For many years, ß-blockers have been used to treat patients with coronary heart disease. In patients with stable angina, the effect of ß-blockers on the amino acid spectrum of blood serum has been studied. Its violation is considered as one of the pathogenetic links in the development of atherosclerosis. The study showed a more efficient action of nebivolol compared to bisoprolol on the amino acid imbalance. In patients with stable angina against the background of antianginal therapy, which included bisoprolol and nebivolol, there was a significant decrease in the total amount of amino acids, the amount of essential amino acids, and the amount of essential amino acids compared to the treatment. Against the background of the nebivolol treatment, there is a positive dynamics of sulfur-containing amino acids (methionine level was maintained, taurine level was significantly increased, cystine level was normalized), isoleucine level was normalized, which indirectly indicates cardioprotective and angiprotective effect of nebivolol.

Lanthanum Hydroxide Protects Kidney Through Gut-Metabolite-Kidney Axis in a Rat Model of CKD

Background: Recent evidence suggests alterations in the gut-kidney axis may drive chronic kidney disease (CKD). Results: In the present study, we observed that administration of adenine to rats induced CKD, gut microbial dysbiosis, kidney pathology, and amino acid metabolism. In this model of CKD hyperphosphatemia, lanthanum hydroxide improved kidney function in CKD rats by restoring gut microbial homeostasis, thereby increasing urine ammonium metabolism. These findings demonstrated that lanthanum hydroxide improves kidney function in a CKD model in mice by restoring homeostasis of the gut-metabolite-kidney axis, which alleviated an amino acid imbalance. Lanthanum hydroxide thus shows therapeutic potential for patients with CKD, through reshaping the composition of gut microbiota.Conclusions: Lanthanum hydroxide plays a kidney protective role through the gut-metabolite-kidney axis in a rat model of chronic kidney disease caused by adenine.

The levels of relaxin and amino acids play a critical role in women with variable degree of preparedness for labour

Underlying biochemical factors that contribute towards the preparedness for labour and ripening of the cervix remain largely unknown. We aimed to characterize metabolic and hormonal determinants that constitute the preparedness for labour in women. The aim of the research was to study the content of relaxin and amino acids involved in its formation in primiparous pregnant women with various degrees of birth preparedness. Materials and methods: Prospective study has been conducted on 115 primiparous women at 38-40 weeks of gestation. Biochemical methods were used to analyse relaxin and amino acid levels in pregnant women with varying degree of birth preparedness. Results: the obtained data from the study indicate importance role of relaxin in the underlying pathogenesis in women with variable degree of preparedness for labour. The results allow to use the levels of relaxin serum as a predictor of the state of the birth canal. Furthermore, the amino acids are known to participate in various critical metabolic processes and play an important role is orchestrating many essential pathways in the body. We present the analysis of amino acids involved in the formation of relaxin in the serum of pregnant women. Our analysis has shown that amino acid imbalance leads to disruption of energy metabolism and blood flow rate, resulting in metabolic, structural and functional changes in the cervix at the onset of labour. Conclusion: considering the mechanisms of the possible influence of relaxin and amino acids on the cervical ripening, we concluded that correcting amino acid imbalance and normalising relaxin levels should be included in preinduction of labour therapeutic regimen. This would be an important step in improving the perinatal outcomes

EVALUATION OF BLOOD-RUMEN CONTENT MIXTURE IN THE DIETS OF STARTER CHICKS

A trial with 234 day-old Olympian Black pullet chicks was conducted for a duration of eight weeks to determine the optimum level of inclusion of Blood-Rumen content Mixture (BRC) in the diet of starter chicks. Chicks were fed ad-libitum starter diets containing 0, 5, 10, 15, 20% BRC and another 20% BRC diet containing no soya bean cake. Birds on all BRC-based diets had higher body weight gains and higher feed intakes than birds on the control diet. A progressive increase in feed: gain ratio was observed from 10%BRC to 20% BRC in the diets. The decline in the performance of chicks fed higher levels of BRC in the diet is suggested to be due to the high crude fiber content and possible amino acid imbalance of such diets. The results of this trial shows that starter pullets should not be fed more than 10% BRC.

Branched-Chain Amino Acids and Branched-Chain Keto Acids in Hyperammonemic States: Metabolism and as Supplements

In hyperammonemic states, such as liver cirrhosis, urea cycle disorders, and strenuous exercise, the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) is activated and BCAA concentrations decrease. In these conditions, BCAAs are recommended to improve mental functions, protein balance, and muscle performance. However, clinical trials have not demonstrated significant benefits of BCAA-containing supplements. It is hypothesized that, under hyperammonemic conditions, enhanced glutamine availability and decreased BCAA levels facilitate the amination of branched-chain keto acids (BCKAs; α-ketoisocaproate, α-keto-β-methylvalerate, and α-ketoisovalerate) to the corresponding BCAAs, and that BCKA supplementation may offer advantages over BCAAs. Studies examining the effects of ketoanalogues of amino acids have provided proof that subjects with hyperammonemia can effectively synthesize BCAAs from BCKAs. Unfortunately, the benefits of BCKA administration have not been clearly confirmed. The shortcoming of most reports is the use of mixtures intended for patients with renal insufficiency, which might be detrimental for patients with liver injury. It is concluded that (i) BCKA administration may decrease ammonia production, attenuate cataplerosis, correct amino acid imbalance, and improve protein balance and (ii) studies specifically investigating the effects of BCKA, without the interference of other ketoanalogues, are needed to complete the information essential for decisions regarding their suitability in hyperammonemic conditions.