Abstract
BackgroundCaloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible. It was investigated whether these changes could be a residual effect of the nutritional condition during lactation and what could be the mechanism of such change.MethodsNewborn Wistar rat pups were arranged in litters of 6 or 12 (G6 and G12). After weaning, the male pups were divided in: G6L and G12 L, fed freely until the age of 90 days (freely-fed groups); G6R and G12R, given 50% of the GL ingestion (food-restricted groups) until 90 days of age; G6RL and G12RL, given 50% of the GL ingestion until 60 days of age and fed freely until 90 days of age (refed groups). The experimental protocols were carried out at the age of 90 days after overnight fasting. Pairs of groups were compared through t test; other statistical comparisons were made with one-way ANOVA with Tukey post hoc text.ResultsCaloric restriction was effective in decreasing body and fat weights, total cholesterol and LDL. These effects were totally or partially reversed after 30 days of refeeding (groups GRL). During liver perfusion, the high glucose output of the GRs was further enhanced by adrenaline (1 μM), but not by lactate infusion. In contrast, in groups G6L, G12 L, G6RL and G12RL glycogenolysis (basal and adrenaline-stimulated glucose output) was low and gluconeogenesis from lactate was significant. A twofold increase in liver content of PKA in group G6R suggests that liver sensitivity to glucagon and adrenaline was higher because of caloric restriction, resulting in enhanced glucose output.ConclusionsAs glucose output was not affected by litter size, liver glucose metabolism in the adult rat, in contrast to other metabolic processes, is not a programmed effect of the nutritional condition during lactation. In addition, the increased expression of PKA points to a higher sensitivity of the animals under caloric restriction to glycogenolytic hormones, a relevant condition for glucose homeostasis during fasting.
Highlights
Caloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible
It is evident the effect that the caloric restriction had on body weight, both in G6R and G12R, which were 45–49% less heavy than their corresponding GL (p < 0.05)
Refeeding for 30 days partially reversed the effect of caloric restriction, which GRL weighing 60% more than their corresponding GR (p < 0.05), but still 10–20% less than the GL from the same litter size (p < 0.05)
Summary
Caloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible. It was investigated whether these changes could be a residual effect of the nutritional condition during lactation and what could be the mechanism of such change. Caloric restriction represents a challenge to an organism by limiting the supply of energy and nutrients. Our research group has been investigating changes of systemic and liver glucose metabolism caused by caloric restriction in rats [5,6,7,8]. Caloric restriction since birth was chosen because it is a permanent limited supply of calories and nutrients capable of impairing growth, and other morphological and physiological aspects, such as fat deposition, insulin sensitivity, glucose tolerance and energy metabolism
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