Prediction of Brain and Serum Free Amino Acid Profiles in Rats Fed Graded Levels of Protein

Gustafson, Jon M.; Dodds, Steven J.; Burgus, Roger; Lp, Mercer

doi:10.1093/jn/116.9.1667

Cited by 39 publications

(35 citation statements)

References 10 publications

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“…During growth, the plasma threonine content is positively correlated with the dietary protein level (Gustafson et al, 1986). The same phenomenon was observed during lactation from day 2 after littering.…”

Section: Methodssupporting

confidence: 71%

Effects of protein level, methionine supplementation and carbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat

Leclerc¹,

Chanussot²,

Miller³

et al. 1989

Reprod. Nutr. Dévelop.

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Summary -Eight groups of 13-15 female rats were fed purified diets after littering. Four groups received a low protein (8% casein) diet (groups 8) and the others, a normal protein (20% casein) diet (groups 20). Carbohydrates were supplied either as starch (groups S) or as starch plus 40% fructose (groups F). Half the animals received a 0.4% methionine supplementation (groups M). Four or five dams per group were sacrificed on days 2, 7 and 14 after littering.The diet intake was increased by methionine supplementation, substitution of starch for fructose and increased protein content, mainly during the second week of lactation. This influenced weight variation of the dams and litter growth.On all days, the plasma levels of cholesterol esters, triglycerides and phospholipids were positively correlated with the dietary protein level.On days 7 and 14, the liver neutral lipid content was increased in rats fed the low protein diets supplemented with methionine (groups 8SM and 8FM) and the normal protein diets containing 40% fructosq (groups 20F and 20FM).The plasma free threonine content was positively correlated with the protein level in the diet. On day 14, rats fed a low protein diet had a threonine deficiency, except those in groups 8S and 8F. The plasma free threonine content of these rats was not reduced, possibly due to an impaired utilization of this amino acid.The liver lipidosis observed during lactation, in contrast to that observed during growth with a low protein diet, was not due to a threonine deficiency.

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Section: Methodssupporting

confidence: 71%

Effects of protein level, methionine supplementation and carbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat

Leclerc¹,

Chanussot²,

Miller³

et al. 1989

Reprod. Nutr. Dévelop.

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“…Brain amino acid concentrations are sensitive to changes in dietary amino acid availability as well as the concentrations of amino acids within the circulation, which supports the possibility that the brain could be directly sensitive to changes in amino acid availability (4,6,13). To discriminate between a direct effect of amino acids on the brain vs. an indirect effect within the periphery, third-ventricular cannulas were used to directly deliver amino acids in the brain, thus bypassing any peripheral sensing mechanism.…”

Section: Discussionmentioning

confidence: 94%

Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

Morrison¹,

Xi²,

White³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

159

115

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Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low-protein diet (10% of calories) exhibited increased food intake ( P < 0.05) and hypothalamic Agouti-related protein ( Agrp) gene expression ( P = 0.002). Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 μg) suppressed 24-h food intake ( P < 0.05), indicating that increasing amino acid concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1–7 hypothalamic cells were exposed to low amino acids for 16 h. Decreasing amino acid availability increased Agrp mRNA levels in GT1–7 cells ( P < 0.01), and this effect was attenuated by replacement of the amino acid leucine ( P < 0.05). Acute exposure to elevated amino acid concentrations increased ribosomal protein S6 kinase phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mammalian target of rapamycin (mTOR) signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1–7 cells cultured in either low or high amino acids for 16 h and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids ( P = 0.01). Taken together, these observations indicate that amino acids can act within the brain to inhibit food intake and that a direct, mTOR-dependent inhibition of Agrp gene expression may contribute to this effect.

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“…In addition to their primary function in protein synthesis, specific amino acids, including glutamate and aspartate, function as excitatory signals in the central nervous system. In part because of these dual functions, amino acid pools in the brain are rigorously regulated (4,9,27).…”

Section: Discussionmentioning

confidence: 99%

The GCN2 eIF2α Kinase Is Required for Adaptation to Amino Acid Deprivation in Mice

Zhang

McGrath

Reinert

et al. 2002

Molecular and Cellular Biology

401

318

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The GCN2 eIF2␣ kinase is essential for activation of the general amino acid control pathway in yeast when one or more amino acids become limiting for growth. GCN2's function in mammals is unknown, but must differ, since mammals, unlike yeast, can synthesize only half of the standard 20 amino acids. To investigate the function of mammalian GCN2, we have generated a Gcn2 ؊/؊ knockout strain of mice. Gcn2 ؊/؊ mice are viable, fertile, and exhibit no phenotypic abnormalities under standard growth conditions. However, prenatal and neonatal mortalities are significantly increased in Gcn2 ؊/؊ mice whose mothers were reared on leucine-, tryptophan-, or glycine-deficient diets during gestation. Leucine deprivation produced the most pronounced effect, with a 63% reduction in the expected number of viable neonatal mice. Cultured embryonic stem cells derived from Gcn2 ؊/؊ mice failed to show the normal induction of eIF2␣ phosphorylation in cells deprived of leucine. To assess the biochemical effects of the loss of GCN2 in the whole animal, liver perfusion experiments were conducted. Histidine limitation in the presence of histidinol induced a twofold increase in the phosphorylation of eIF2␣ and a concomitant reduction in eIF2B activity in perfused livers from wild-type mice, but no changes in livers from Gcn2 ؊/؊ mice.

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Prediction of Brain and Serum Free Amino Acid Profiles in Rats Fed Graded Levels of Protein

Cited by 39 publications

References 10 publications

Effects of protein level, methionine supplementation and carbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat

Effects of protein level, methionine supplementation and carbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat

Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

The GCN2 eIF2α Kinase Is Required for Adaptation to Amino Acid Deprivation in Mice

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