Ingrid D. Schweigert

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.

Glycine, serine, and leucine metabolism in different regions of rat central nervous system.

We have investigated the glycine, serine and leucine metabolism in slices of various rat brain regions of 14-day-old or adult rats, using [1-14C]glycine, [2-14C]glycine, L-[3-14C]serine and L-[U-14C]leucine. We showed that the [1-14C]glycine oxidation to CO2 in all regions studied occurs almost exclusively through its cleavage system (GCS) in brains of both 14-day-old and adults rats. In 14-day-old rats, the highest oxidation of [1-14C]glycine was in cerebellum and the lowest in medulla oblongata. In these animals, the L-[U-14C]leucine oxidation was lower than the [1-14C]glycine oxidation, except in medulla oblongata where both oxidations were the same. Serine was the amino acid that showed lowest oxidation to CO2 in all structure studied. In adult rats brains, the highest oxidation of [1-14C]glycine was in cerebral cortex and the lowest in medulla oblongata. We have not seen difference in the lipid synthesis from both glycine labeled, neither in 14-day-old rats nor in adult ones, indicating that the lipids formed from glycine were not neutral. Lipid synthesis from serine was significantly high than lipid synthesis and from all other amino acids studied in all studied structures. Protein synthesis from L-[U-14C]leucine was significantly higher than that from glycine in all regions and ages studied.

Study of developmental changes on hexoses metabolism in rat cerebral cortex

We have studied the developmental changes of glucose, mannose, fructose and galactose metabolism in rat cerebral cortex. As the animals aged, glucose, mannose and fructose oxidation to CO2 increased, whereas galactose oxidation decreased. Lipid synthesis from glucose and fructose also increased with age, that from mannose decreased and galactose did not change. Cytochalasin B, a potent non-competitive inhibitor of sodium-independent glucose transport, significantly impaired glucose, mannose and galactose metabolism, but had no effect on fructose metabolism. Both galactose or fructose did not change, whereas mannose declined the glucose metabolism. Glucose decreased fructose, galactose and mannose metabolism. Our results show that besides glucose, the metabolism of mannose, galactose and fructose present developmental changes from fetal to adult age, and reinforce the literature data indicating that mannose and galactose are transported by glucose carriers, while fructose is not.

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+]0 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 μM) 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.

Desnutrição, maturação do sistema nervoso central e doenças neuropsiquiátricas

Nutrition has a profound impact on the development of cerebral structures and functions. Over and above the metabolic programming induced by fetal malnutrition in order to increase the chances of survival of the fetus in post-natal life, studies point to pre-natal nutritional deficiency as a risk factor for the development of neuropsychiatric diseases. The present review aims to consider aspects of malnutrition in relation to cerebral development, the temporal and functional extension of its impact, as well as establishing correlations with neuropsychiatric diseases, considering articles of periodicals enlisted by Medline from 1962 to 2005. Events arising from early malnutrition display, for the most part, a permanent character to some degree, if not immediate, prospective and compromising of biochemical, physiological and behavioral performance. Despite the apparent delays in the development of neurological parameters, these do not represent mere isolated functional errors, as the ideal inter-relations and connections are influenced, extending the temporal errors of the occurrence of events. The impression of the mark of malnutrition at the level of the genetic code, in extending the horizon of the effects of malnutrition to a multigenerational level, amplifies its effects. Aspects characterized as compensatory mechanisms, while, on the one hand they display an ability to adapt to severe early stress, on the other they may be compromised in the eventuality of additional environmental or emotional stress. Concern with regard to the subliminal or expressive effects of neuropsychiatric diseases on the quality of life consolidate the importance of the development of research aimed at understanding and elucidating the impacts and mechanisms that modulate the effects of malnutrition on neurodevelopment.