Gestational and postnatal low protein diet alters insulin sensitivity in female rats.

Nutrition during pregnancy and lactation can program an offspring's metabolism with regard to glucose and lipid homeostasis. A suboptimal environment during fetal, neonatal and infant development is associated with impaired glucose tolerance, type 2 diabetes and insulin resistance in later adult life. However, studies on the effects of a low protein diet imposed from the beginning of gestation until adulthood are scarce. This study's objective was to investigate the effects of a low protein diet imposed from the gestational period until 4 months of age on the parameters of glucose tolerance and insulin responsiveness in Wistar rats. The rats were divided into a low protein diet group and a control group and received a diet with either 7% or 25% protein, respectively. After birth, the rats received the same diet as their mothers, until 4 months of age. In the low protein diet group it was observed that: (i) the hepatic glycogen concentration and hepatic glycogen synthesis from glycerol were significantly greater than in the control group; (ii) the disposal of 2-deoxyglucose in soleum skeletal muscle slices was 29.8% higher than in the control group; (iii) there was both a higher glucose tolerance in the glucose tolerance test; and (iv) a higher insulin responsiveness in than in the control group. The results suggest that the low protein diet animals show higher glucose tolerance and insulin responsiveness relative to normally nourished rats. These findings were supported by the higher hepatic glycogen synthesis and the higher disposal of 2-deoxyglucose in soleum skeletal muscle found in the low protein diet rats.

Effect of 2-deoxy-D-glucose on aminoacids metabolism in rats' cerebral cortex slices.

We studied the effect of different concentrations of 2-deoxy-D-glucose on the L-[U-14C]leucine, L-[1-14C]leucine and [1-14C]glycine metabolism in slices of cerebral cortex of 10-day-old rats. 2-deoxy-D-glucose since 0.5 mM concentration has inhibited significantly the protein synthesis from L-[U-14C]leucine and from [1-14C]glycine in relation to the medium containing only Krebs Ringer bicarbonate. Potassium 8.0 mM in incubation medium did not stimulate the protein synthesis compared to the medium containing 2.7 mM, and at 50 mM diminishes more than 2.5 times the protein synthesis compared to the other concentration. Only at the concentration of 5.0 mM, 2-deoxy-D-glucose inhibited the CO2 production and lipid synthesis from L-[U-14C] leucine. This compound did not inhibit either CO2 production, or lipid synthesis from [1-14C]glycine. Lactate at 10 mM and glucose 5.0 mM did not revert the inhibitory effect of 2-deoxy-D-glucose on the protein synthesis from L-[U-14C]leucine. 2-deoxy-D-glucose at 2.0 mM did not show any effect either on CO2 production, or on lipid synthesis from L-[U-14C]lactate 10 mM and glucose 5.0 mM.

Effects of protein malnutrition on oxidative status in rat brain.

OBJECTIVES: This study evaluated the effects of protein malnutrition on oxidative status in rat brain areas. METHODS: We investigated various parameters of oxidative status, free radical content (dichlorofluorescein formation), indexes of damage to lipid (thiobarbituric acid-reactive substances assay), and protein damage (tryptophan and tyrosine content) in addition to total antioxidant reactivity levels and antioxidant enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase in different cerebral regions (cortex, hippocampus, and cerebellum) from rats subjected to prenatal and postnatal protein malnutrition (control 25% casein and protein malnutrition 7% casein). RESULTS: Protein malnutrition altered various parameters of oxidative stress, especially damage to macromolecules. Free radical content was unchanged by protein malnutrition. There was an increase in levels of thiobarbituric acid-reactive substances, the index of lipid peroxidation, in the cerebellum and cerebral cortex (P < 0.05) from protein-malnourished rats. Moreover, significant decreases in tryptophan and tyrosine in all tested brain structures (P < 0.05) were observed. Catalase activity was significantly decreased in the cerebellum (P < 0.05). In addition, a significant decrease in total antioxidant reactivity levels (P < 0.05) was observed in the cerebral cortex from protein-malnourished rats. CONCLUSIONS: The present data indicated that protein malnutrition increased oxidative damage to lipids and proteins from the studied brain areas. These results may be an indication of an important mechanism for changes in brain development that are caused by protein malnutrition.

Gestational and postnatal malnutrition affects sensitivity of young rats to picrotoxin and quinolinic acid and uptake of GABA by cortical and hippocampal slices.

It is widely known that a complex interaction between excitatory and inhibitory systems is required to support the adequate functioning of the brain and that significant alterations induced by early protein restriction are complex, involving many systems. Based on such assumptions, we investigated the effects of maternal protein restriction during pregnancy and lactation followed by offspring protein restriction on some GABAergic and glutamatergic parameters, which mediate inhibitory and excitatory transmission, respectively. The sensitivity of young malnourished rats to convulsant actions of the GABA(A) receptor antagonist picrotoxin (PCT; s.c.) and to N-methyl-d-aspartate (NMDA) receptor agonist quinolinic acid (QA; i.c.v) and also gamma-amino-n-butyric acid (GABA) and glutamate uptake by cortical and hippocampal slices were evaluated in P25 old rats. Early protein malnutrition induced higher sensitivity to picrotoxin, which could be associated with the observed higher GABA uptake by cortical, and hippocampal slices in malnourished rats. In contrast, we observed lower sensitivity to quinolinic acid in spite of unaltered glutamate uptake by the same cerebral structures. Picrotoxin enhanced GABA uptake in hippocampus in well- and malnourished rats; however, it did not affect cortical GABA uptake. Our data corroborate our previous report, showing that malnutrition depresses the glutamatergic activity, and point to altered modulation of GABAergic neurotransmission. Such findings allow us to speculate that malnutrition may affect the excitatory and inhibitory interaction.

High extracellular K+ levels stimulate acetate oxidation in brain slices from well and malnourished rats.

We investigated the effect of high (12, 20, and 50 mM) extracellular K+ concentrations ([K+]0) on [U-14C] acetate oxidation to CO2 in cerebral cortex slices of control and perinatal malnourished rats. High [K+]o increased the acetate oxidation, compared with a medium containing 2.7 mM [K+]0. By investigating the mechanisms involved in this stimulation, it was shown that (i) ouabain (1 mM) and monensin (10 microM) prevented this increase; (ii) in a medium with physiological [K+]0 (2.7 mM), the decreasing of [Na+]0 stimulated acetate oxidation. These results suggest that the stimulatory effect of [K+]0 on acetate oxidation was due to the decreasing of Na1 levels. Considering that malnutrition could alter the activity of Na+,K(+)-ATPase and/or other pertinent proteins, its effect on acetate oxidation was investigated. The malnutrition, which altered the body and cerebral weight of rats, did not modify the acetate oxidation in any protocol.