scholarly journals Characterization of homocysteine metabolism in the rat liver

2000 ◽  
Vol 350 (3) ◽  
pp. 685-692 ◽  
Author(s):  
Lori M. STEAD ◽  
Margaret E. BROSNAN ◽  
John T. BROSNAN

Recent evidence suggests that an increased plasma concentration of the sulphur amino acid homocysteine is a risk factor for the development of vascular disease. The tissue(s) responsible for homocysteine production and export to the plasma are not well known. However, given the central role of the liver in amino acid metabolism, we developed a rat primary hepatocyte model in which homocysteine (and cysteine) production and export were examined. The dependence of homocysteine export from incubated hepatocytes on methionine concentration fitted well to a rectangular hyperbola, with half-maximal homocysteine export achieved at methionine concentrations of approx. 0.44mM. Hepatocytes incubated with 1mM methionine and 1mM serine (a substrate for the transulphuration pathway of homocysteine removal) produced and exported significantly less homocysteine (25–40%) compared with cells incubated with 1mM methionine alone. The effects of dietary protein on homocysteine metabolism were also examined. Rats fed a 60% protein diet had a significantly increased total plasma homocysteine level compared with rats fed a 20% protein diet. Invitro effects of dietary protein were examined using hepatocytes isolated from animals maintained on these diets. When incubated with 1mM methionine, hepatocytes from rats fed the high protein diet exported significantly more homocysteine compared with hepatocytes from rats fed the normal protein diet. Inclusion of serine significantly lowered homocysteine export in the normal protein group, but the effect was more marked in the high protein group. Invivo effects of serine were also examined. Rats fed a high protein diet enriched with serine had significantly lower total plasma homocysteine (25–30%) compared with controls. These data indicate a significant role for the liver in the regulation of plasma homocysteine levels.

1990 ◽  
Vol 258 (5) ◽  
pp. R1095-R1100 ◽  
Author(s):  
B. S. Daniels ◽  
T. H. Hostetter

Vasoactive hormonal response to two levels of dietary protein intake was studied in seven healthy adult volunteers. The subjects were randomly placed on a 2-g.kg-1.day-1 (high) or 0.55-g.kg-1.day-1 (low) diet using a crossover design and were studied on the morning of the 5th day and again after 24 h of indomethacin treatment. Plasma renin activity (PRA), aldosterone, vasopressin, and urinary excretion of 6-ketoprostaglandin F1 alpha (PGF1 alpha) were significantly higher on the high-protein diet despite constancy of body weight, blood pressure, pulse, urinary sodium and potassium excretion, and plasma amino acid levels. After treatment with cyclooxygenase inhibitor indomethacin, 6-keto-PGF1 alpha excretion was equalized, but the elevated PRA and aldosterone levels persisted on the high-protein diet, suggesting that PRA and aldosterone elevations do not depend entirely on prostanoid release. We conclude that chronic augmentation of dietary protein intake is accompanied by alterations of vasoactive hormones, which persist for up to 10 h postprandially and are independent of elevated plasma amino acid levels. Such hormonal alterations may mediate some of the dietary protein-mediated changes in renal hemodynamics.


1978 ◽  
Vol 176 (2) ◽  
pp. 623-626 ◽  
Author(s):  
E A Newsholme ◽  
T Williams

Starvation or feeding rats on a high-protein diet, valine or isoleucine, but not leucine, increases the activity of muscle phosphoenolpyruvate carboxykinase, but has no effect on NADP+-linked malate dehydrogenase. This suggests that muscle phosphoenolpyruvate carboxykinase is involved in oxidation or conversion of some amino acids to alanine.


1960 ◽  
Vol 198 (2) ◽  
pp. 354-356
Author(s):  
L. Fragola ◽  
D. F. Magee

Rats with separation of the pancreatic ducts and sham-operated controls were fed 8% and 30% casein diet. The fecal fats were lowered by the high-protein diet in each case. The magnitude of the decrease was not different in the two groups. The experiment was repeated with the addition of 2% cholesterol to the two diets. Both groups of animals while on the high-protein diet had less fecal cholesterol than when on the low-protein regimen.


1995 ◽  
Vol 48 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Joseph Caverzasio ◽  
T. Shigematsu ◽  
R. Rizzoli ◽  
Jean-Philippe Bonjour

2019 ◽  
Vol 317 (6) ◽  
pp. E1015-E1021 ◽  
Author(s):  
Tristan Chalvon-Demersay ◽  
Joanna Moro ◽  
Patrick C. Even ◽  
Catherine Chaumontet ◽  
Daniel Tomé ◽  
...  

General control nonderepressible 2 (GCN2) is a kinase that detects amino acid deficiency and is involved in the control of protein synthesis and energy metabolism. However, the role of hepatic GCN2 in the metabolic adaptations in response to the modulation of dietary protein has been seldom studied. Wild-type (WT) and liver GCN2-deficient (KO) mice were fed either a normo-protein diet, a low-protein diet, or a high-protein diet for 3 wk. During this period, body weight, food intake, and metabolic parameters were followed. In mice fed normo- and high-protein diets, GCN2 pathway in the liver is not activated in WT mice, leading to a similar metabolic profile with the one of KO mice. On the contrary, a low-protein diet activates GCN2 in WT mice, inducing FGF21 secretion. In turn, FGF21 maintains a high level of lipid oxidation, leading to a different postprandial oxidation profile compared with KO mice. Hepatic GCN2 controls FGF21 secretion under a low-protein diet and modulates a whole body postprandial oxidation profile.


Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 514 ◽  
Author(s):  
Sandra Vidal-Lletjós ◽  
Mireille Andriamihaja ◽  
Anne Blais ◽  
Marta Grauso ◽  
Patricia Lepage ◽  
...  

Mucosal healing after an inflammatory flare is associated with lasting clinical remission. The aim of the present work was to evaluate the impact of the amount of dietary protein on epithelial repair after an acute inflammatory episode. C57BL/6 DSS-treated mice received isocaloric diets with different levels of dietary protein: 14% (P14), 30% (P30) and 53% (P53) for 3 (day 10), 6 (day 13) and 21 (day 28) days after the time of colitis maximal intensity. While the P53 diet worsened the DSS- induced inflammation both in intensity and duration, the P30 diet, when compared to the P14 diet, showed a beneficial effect during the epithelial repair process by accelerating inflammation resolution, reducing colonic permeability and increasing epithelial repair together with epithelial hyperproliferation. Dietary protein intake also impacted mucosa-adherent microbiota composition after inflammation since P30 fed mice showed increased colonization of butyrate-producing genera throughout the resolution phase. This study revealed that in our colitis model, the amount of protein in the diet modulated mucosal healing, with beneficial effects of a moderately high-protein diet, while very high-protein diet displayed deleterious effects on this process.


2001 ◽  
Vol 52 (7) ◽  
pp. 791
Author(s):  
L. Ma ◽  
F. R. Dunshea ◽  
Y. M. Brockwell ◽  
R. L. Inglis ◽  
D. J. Kingston ◽  
...  

Plasma hormone concentrations were measured in gilts after fasting, long-term protein restriction, or supplementation. In 11-week-old pigs fasted overnight, plasma insulin, glucagon, gastrin, urea, and glucose were increased 30 min after re-feeding (P < 0.05), whereas IGF-I did not change. In 16-week-old gilts fed a standard commercial diet [14.6% crude protein (CP)], or a high-protein diet (16.7% CP) for 4 weeks, the high-protein diet increased weight gain (13%; P < 0.05) and carcass weight (4%; P < 0.05), but did not alter plasma IGF-I, insulin, or glucagon. In 10-week-old gilts fed high-protein diets (19.4% and 18.3% CP), or low-protein diets (15.5% and 13.3% CP) for 12 weeks during the grower and finisher phases, respectively, the low-protein diet decreased weight gain (18%; P < 0.001) and carcass weight (11%; P < 0.01), with a marked increase in plasma glucagon (P < 0.05), no change in insulin, and only a trend towards decreased IGF-I (P = 0.1). The pigs were more sensitive to altered dietary protein at 10 weeks of age than at 16 weeks. Plasma IGF-I was not responsive to the short-term effects of feeding or the long-term effects of dietary protein. Glucagon could provide a useful marker for nutritional status in young pigs, provided that time of feeding is taken into account.


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