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

Abstract 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.

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

10.21203/rs.2.21577/v3 ◽

2020 ◽

Author(s):

Lila Otani ◽

Hiroki Nishi ◽

Ayaka Koyama ◽

Yuta Akasaka ◽

Yusuke Taguchi ◽

...

Keyword(s):

Amino Acid ◽

Fatty Liver ◽

Wistar Rats ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Total Amino Acid ◽

Acid Diet ◽

Low Protein ◽

Lipoprotein Secretion ◽

Amino Acid Diet

Abstract 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.

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

10.21203/rs.2.21577/v2 ◽

2020 ◽

Author(s):

Lila Otani ◽

Hiroki Nishi ◽

Ayaka Koyama ◽

Yuta Akasaka ◽

Yusuke Taguchi ◽

...

Keyword(s):

Amino Acid ◽

Fatty Liver ◽

Wistar Rats ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Total Amino Acid ◽

Acid Diet ◽

Hepatic Fat ◽

Amino Acid Imbalance ◽

Amino Acid Diet

Abstract 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.

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Low Protein, High Essential Amino Acid Diet for Nitrogen Equilibrium in Chronic Dialysis

American Journal of Clinical Nutrition ◽

10.1093/ajcn/21.6.618 ◽

1968 ◽

Vol 21 (6) ◽

pp. 618-625 ◽

Cited By ~ 5

Author(s):

J. H. SHINABERGER ◽

H. EARL GINN

Keyword(s):

Amino Acid ◽

Essential Amino Acid ◽

Chronic Dialysis ◽

Acid Diet ◽

Low Protein ◽

Amino Acid Diet

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0922 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Christophe Barba ◽

Christophe Soulage ◽

Griet Glorieux ◽

Cecile PICARD ◽

Denis Fouque ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Amino Acid ◽

Kidney Disease ◽

Aromatic Amino Acid ◽

Uremic Toxins ◽

Kidney Fibrosis ◽

Acid Diet ◽

Low Protein ◽

Amino Acid Diet

Abstract 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).

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Liver denervation attenuates the hypophagia produced by an imbalanced amino acid diet

Physiology & Behavior ◽

10.1016/0031-9384(95)02168-x ◽

1996 ◽

Vol 59 (4-5) ◽

pp. 925-929 ◽

Cited By ~ 14

Author(s):

L Bellinger

Keyword(s):

Amino Acid ◽

Acid Diet ◽

Amino Acid Diet

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The relative effects of a low-protein-high-carbohydrate diet on the free amino acid composition of liver and muscle

British Journal Of Nutrition ◽

10.1017/s0007114500020213 ◽

1976 ◽

Vol 36 (2) ◽

pp. 219-230

Author(s):

P. G. Lunn ◽

R. G. Whitehead ◽

B. A. Baker

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Free Amino Acid ◽

Acid Concentration ◽

Free Amino ◽

Essential Amino Acids ◽

Protein Diet ◽

Low Protein Diet ◽

Total Amino Acid ◽

Low Protein

1. Free amino acid concentrations in the plasma have been compared with those in liver and quadriceps muscle, in rats fed on diets containing 209 (control) and 31 (low-protein) g protein/kg. The effects of the low-protein diet on diurnal variations in these values were also measured.2. In the plasma, the total amino acid concentration was significantly lower in animals given the low-protein diet, at all times of day except 12.00 hours. In the liver, and to a lesser extent the muscle, total amino acid concentration was maintained.3. In the control animals, diurnal variation in the concentrations of both essential and non-essential amino acids was very similar in plasma, liver and muscle. In animals given the low-protein diet, although the same diurnal pattern was maintained for non-essential amino acids, that occurring among the essential amino acids had virtually disappeared.4. In plasma, the mean 24 h concentration of essential amino acids decreased from 24· mmol/l in control animals to only 1·29 mmol/l in the low-protein-fed animals. Concentrations in muscle and liver were reduced by a similar proportion (from 8·6 to 5·56 μmol/g and from 8·67 to 5·05 μmol/g respectively). Conversely the concentrations of non-essential amino acids in animals given the low-protein diet were increased in plasma (from 1·53 to 2·00 mmol/l), muscle (from 12·5 to 14·3 μmol/g), and liver (from 16·8 to 20·5 μmol/g), muscle showing the lowest increase.5. With the exceptions of lysine, threonine, cystine and tyrosine, the concentrations of all other essential amino acids were reduced more in liver than in muscle. The relationship between this and the failure to maintain plasma albumin concentrations is discussed.

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