Low-protein diet during gestation and lactation increases hepatic lipid accumulation through autophagy and histone deacetylase

2020 ◽  
Vol 319 (1) ◽  
pp. E11-E25
Author(s):  
Huan Wang ◽  
Guanying Bianca Xu ◽  
Diego Hernández-Saavedra ◽  
Hong Chen ◽  
Yuan-Xiang Pan
Keyword(s):  
Amino Acid ◽  
Histone Deacetylase ◽  
Lipid Accumulation ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Density ◽  
Hepatic Lipid ◽  
Low Protein ◽  
Triglyceride Accumulation ◽  
Autophagic Degradation

The present study examined the mechanism of a low-protein (LP) diet on hepatic lipid metabolism during gestation and lactation. Timed-pregnant Sprague-Dawley rats were fed a control or an LP diet during gestation and lactation. LP dams had increased hepatic triglyceride accumulation and a significantly higher aspartate/alanine transaminase ratio, accompanied by a decrease in the circulating very low-density/low-density lipoprotein ratio. Microtubule-associated protein 1 light-chain 3β (LC3B) expression was stimulated in LP dams along with increased histone acetylation. LP diet induced colocalization of the LC3 binding motif interacting proteins apolipoprotein B (APOB) or microsomal triglyceride transfer protein (MTTP) with LC3B, suggesting autophagic degradation. Histone deacetylase 3 (HDAC3) is found necessary to prevent lipid accumulation in response to amino acid deprivation in HepG2 cells. LC3B-mediated APOB protein degradation is related to increases in lipid accumulation. HDAC3 regulated LC3B-induced lipid accumulation potentially through autophagic degradation of APOB and MTTP in response to amino acid limitation caused by a low-protein diet.

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

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.

scholarly journals Serum metabolites associated with dietary protein intake: results from the Modification of Diet in Renal Disease (MDRD) randomized clinical trial

2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Dietary Protein ◽  
Protein Intake ◽  
Filtration Rate ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Dietary Protein Intake ◽  
Low Protein ◽  
P 16

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.

Plasma Insulin and Amino Acid Concentrations in Rats Given an Adequate or Low Protein Diet

1973 ◽  
Vol 103 (5) ◽  
pp. 720-729 ◽  
Author(s):  
Vernon R. Young ◽  
Gaston Vilaire ◽  
Paul M. Newberne ◽  
Robert B. Wilson
Keyword(s):  
Amino Acid ◽  
Plasma Insulin ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein ◽  
Amino Acid Concentrations

scholarly journals The regulation of protein synthesis in the liver of rats. Mechanisms of dietary amino acid control in the immature animal

1968 ◽  
Vol 107 (5) ◽  
pp. 615-623 ◽  
Author(s):  
R. W. Wannemacher ◽  
W. K. Cooper ◽  
M. B. Yatvin
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Specific Radioactivity ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Deficient Diet ◽  
Low Protein ◽  
Rna Content ◽  
Cytoplasmic Rna

Weanling (23-day-old) rats were fed either on an amino acid-deficient diet (6% of casein, which in effect represents an ‘amino acid-deficient’ diet) or on a diet containing an adequate amount of protein (18% of casein) for 28 days. The hepatic cells from the animals fed on the low-protein diet were characterized by low amino acid content, almost complete inhibition of cell proliferation and a marked decrease in cell volume, protein content and concentration of cytoplasmic RNA compared with cells from control rats. The lower concentration of cytoplasmic RNA was correlated with a decreased ribosomal-RNA content, of which a larger proportion was in the form of free ribosomes. The protein-synthetic competence and messenger-RNA content of isolated ribosomes from liver cells of protein-deprived animals were 40–50% of those noted in controls. At 1hr. after an injection of radioactive uridine, the specific radioactivity of liver total RNA was greater in the group fed on the low-protein diet, but the amount of label that was associated with cytoplasmic RNA or ribosomes was significantly less than that noted in control animals. From these data it was concluded that dietary amino acids regulate hepatic protein synthesis (1) by affecting the ability of polyribosomes to synthesize protein and (2) by influencing the concentration of cytoplasmic ribosomes. It is also tentatively hypothesized that the former process may be directly related to the concentration of cellular free amino acids, whereas the latter could be correlated with the ability of newly synthesized ribosomal sub-units to leave the nucleus.

scholarly journals No protein intake compensation for insufficient indispensable amino acid intake with a low-protein diet for 12 days

2014 ◽  
Vol 11 (1) ◽  
pp. 38 ◽  
Author(s):  
Eveline A Martens ◽  
Sze-Yen Tan ◽  
Richard D Mattes ◽  
Margriet S Westerterp-Plantenga
Keyword(s):  
Amino Acid ◽  
Protein Intake ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Acid Intake ◽  
Low Protein ◽  
Indispensable Amino Acid ◽  
Amino Acid Intake
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