Effect of amino acid blend as alternative to antibiotics for growing pigs

This study aimed to evaluate the effect of supplementing arginine (Arg) + glutamine (Gln) replacing antibiotics on performance, immune response, and antioxidant capacity of pigs in the growing phase. One hundred and fifty 63-d-old pigs with initial body weight (BW) of 25.0 ± 1.46 kg were distributed in a randomized block design, with three treatments and ten replicates. The three diets were control; antibiotic, control + 100 mg/kg tiamulin and 506 mg/kg oxytetracycline; amino acid, control + 10 g/kg Arg and 2 g/kg Gln. Dietary treatments were fed from 63 to 77 d. Following the treatment period, all pigs were fed the control diet from 77 to 90 d. Data were analyzed using GLIMMIX and UNIVARIATE in SAS 9.4. From 63 to 70 d, pigs fed diets with antibiotics had improved (P < 0.05) average daily feed intake (ADFI), average daily weight gain (ADG), gain to feed ratio (G:F), and 70 d BW compared to those fed control or amino acid diets. From 70 to 77 d, including antibiotics in the diet increased (P < 0.05) ADG and 77 d BW. From 77 to 90 d, pigs fed the amino acid diet had greater (P < 0.05) ADG and ADFI than those fed an antibiotic diet. From 63 to 90 d, although pig performance was not affected (P > 0.05), growth curve of pigs fed the antibiotic diets was different (P < 0.05) from those fed the control and amino acids diets. At 70 d, serum tumor necrosis factor-α and diamine oxidase (DAO) were lower (P < 0.05) in pigs fed the antibiotic diet than the control diet, and pigs fed the amino acid diet had intermediate results. Ferric reducing antioxidant power (FRAP) was lower (P < 0.05) in pigs fed the amino acid diet than the antibiotic diet, and pigs fed the control diet had intermediate results. At 70 and 77 d, serum urea nitrogen was higher (P < 0.05) in pigs fed the amino acid diet. At 77 d, DAO and serum immunoglobulin G was lower (P < 0.05) in pigs fed the antibiotic diet. FRAP was lower (P < 0.05) in pigs fed the amino acid and control diets. Serum malondialdehyde was higher (P < 0.05) in pigs fed the amino acid diet than those fed the control diet, and pigs fed the antibiotic diet had intermediate results. At 90 d, antibiotics or amino acids did not affect (P > 0.05) serum parameters. Amino acid blend supplementation at the selected doses in this study did not positively affect growing pigs. Although from 63 to 77 d, antibiotics improved performance, when considering the overall study period, growing pigs did not benefit from a diet containing antibiotics.

A low aromatic amino-acid diet improves renal function and prevent kidney fibrosis in mice with chronic kidney disease

Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition.

A Low Aromatic Amino-Acid Diet Improves Renal Function and Prevent Kidney Fibrosis in Mice with Chronic Kidney Disease

Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in uremic toxins production, with a lower risk of malnutrition.

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Background: Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.Methods: We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks.Results: Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis.Conclusions: Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Background Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models. Methods We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks. Results Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis. Conclusions : Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

P0922A LOW AROMATIC AMINO-ACID DIET IMPROVES RENAL FUNCTION AND PREVENTS KIDNEY FIBROSIS IN MICE WITH CHRONIC KIDNEY DISEASE

Background and Aims Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), the mechanisms through which it delays the progression to end-stage renal disease (ESRD) remain controversial. A reduced production of uremic toxins could contribute to the benefits of the LPD. Aromatic amino-acids are precursors of major uremic toxins such as p-cresyl sulfate (PCS), indoxyl sulfate (IS), indole-3-acetic acid or phenol. We investigated the hypothesis that a low aromatic amino acid diet (LAA, namely low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the specific diminution of uremic toxins production. Method Renal failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Thereafter, they received 3 different diets for 6 weeks: normoproteic diet (NPD: 14.7% proteins, aromatics 0.019%), LPD (5% proteins, aromatics 0.007%) and LAA (14% proteins, aromatics 0.007%). Results LAA and LPD had no significant effect on body weight. Plasma creatinine was significantly lower in LPD and LAA groups compared to NPD group (72 ± 4 and 73 ± 4 µmol/L vs 127 ± 6 µmol/L, p<0.0001), as well as proteinuria (1.3 ± 0.3 and 1.2 ± 0.1 mg/24h vs 3.8 ± 0.9 mg/24h, p<0.05). Kidney fibrosis was more severe in NPD group vs LPD and LAA groups (17 ± 1% vs 10 ± 1 % and 13 ± 2 %, p<0.0001 and p=0.01). Kidney inflammation was also reduced with LPD and LAA. Free PCS and IS were lower in LPD and LAA groups compared to NPD group. Conclusion These results suggest that LAA confers similar benefits as compared with those of LPD to delay the progression of CKD through reduction of uremic toxins production, with lower risk of malnutrition. Renal function and urinary protein excretion in control and CKD mice Serum creatinine (A), blood urea nitrogen (B) and urinary proteins (C) in control and CKD mice fed with normoproteic diet (NPD), low protein diet (LPD) or low aromatic amino-acid diet (LAA). Data are expressed as mean ± SEM for n = 5-11 animals in each group. *p < 0.05, **p < 0.01, ***p < 0.001 vs CKD-NPD; (two-way ANOVA and Dunnett post hoc test).

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Background Dietary protein deficiency and amino acid uimbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency as well as total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of this fatty liver formation using these two models. Methods A low-total-amino acid diet (equivalent to 5% protein) and a low-arginine diet (solely the arginine content alone is as low as the low-total-amino acid diet) to the rats for 2 weeks. Results There was substantially greater hepatic TG accumulation in the low-arginine group than in the low-total-amino acid group. The low-total-amino-acid diet potentiated insulin signals in the liver and enhanced de novo lipogenesis. By contrast, the low-arginine diet inhibited hepatic very-low-density lipoprotein secretion, without affecting hepatic insulin signaling and lipogenesis. Conclusions We conclude that, although the arginine intake of the low-arginine group was as low as that of the low-total-amino-acid group, these two diets developed a fatty liver via completely different mechanisms. The potentiation of insulin signaling and resultant increases in fatty acid synthesis seem to drive the effects of a low-protein diet, whereas lower VLDL secretion may be the main causes of low-arginine diet-induced TG accumulation in the liver.

Dietary Amino Acids Impact LRRK2-induced Neurodegeneration in Parkinson’s Disease Models

ABSTRACTThe G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of Parkinson’s disease (PD) and results in age-related dopamine neuron loss and locomotor dysfunction in Drosophila melanogaster through an aberrant increase in bulk neuronal protein synthesis. Under non-pathologic conditions, protein synthesis is tightly controlled by metabolic regulation. Whether nutritional and metabolic influences on protein synthesis can modulate the pathogenic effect of LRRK2 on protein synthesis and thereby impact neuronal loss is a key unresolved question. Here, we show that LRRK2 G2019S-induced neurodegeneration is critically dependent on dietary amino acid content. Low dietary amino acid concentration prevents aberrant protein synthesis and blocks LRRK2 G2019S-mediated neurodegeneration in Drosophila and rat primary neurons. Unexpectedly, a moderately high amino acid diet also blocks dopamine neuron loss and motor deficits in Drosophila through a separate mechanism involving stress-responsive activation of 5’-AMP-activated protein kinase (AMPK) and neuroprotective induction of autophagy, implicating the importance of protein homeostasis to neuronal viability. At the highest amino acid diet of the range tested, PD-related neurodegeneration occurs in an age-related manner, but is also observed in control strains, suggesting that it is independent of mutant LRRK2 expression. We propose that dietary influences on protein synthesis and autophagy are critical determinants of LRRK2 neurodegeneration, opening up possibilities for future therapeutic intervention.