Metabolic Imprinting by Maternal Protein Malnourishment Impairs Vagal Activity in Adult Rats

Abstract

Protein restriction during lactation has been suggested to diminish parasympathetic activity, whereas sympathetic activity is enhanced in adult rats. The present study analyses whether dysfunction of the autonomic nervous system is involved in the impairment of insulin secretion from perinatally undernourished rats. Male neonates were reared by mothers fed a low- (4%) protein (LP group) or normal- (23%) protein diet (NP group). At 81 days of age, LP rats showed less body mass than NP rats (318 ± 4 g versus 370 ± 5 g) (P < 0.001). Fat tissue accumulation decreased in LP [0.8 ± 0.03 g/100 g body weight (BW)] compared to NP rats (1.1 ± 0.04 g/100 g BW) (P < 0.001). LP were glucose-intolerant as registered by the area under the curve of an i.v. glucose tolerance test (37 ± 3) compared to NP rats (29 ± 2) (P < 0.05); however, LP animals showed fasting normoglycaemia (LP, 5.0 ± 0.1; NP, 4.9 ± 0.03 mm) and hypoinsulinaemia (LP, 0.10 ± 0.02 ng/ml; NP, 0.17 ± 0.02 ng/ml). LP also showed glucose tissue uptake 60% higher than NP rats (P < 0.05). Vagus firing rate from LP was lower (7.1 ± 0.8 spikes/5 s) than that in NP rats (12.3 ± 0.7 spikes/5 s) (P < 0.001); however, there was no difference in sympathetic nervous activity. The cholinergic insulinotrophic effect was lower in pancreatic islets from LP (0.07 ± 0.01 ng/min/islet) than in NP rats (0.3 ± 0.06 ng/min/islet), whereas the levels of adrenaline-mediated inhibition of glucose-induced insulin release were similar. Perinatal protein restriction inhibited the activity of the vagus nerve, thus reducing the insulinotrophic effect of parasympathetic pathways on pancreatic β-cells, which inhibit insulin secretion.

Low-protein diet in adult male rats has long-term effects on metabolism

“…These results were associated with high electrical firing of the vagus nerve and low sympathetic tonus, indicating the influence of an ANS imbalance on the number and function of adrenergic receptors in the pancreatic b-cells. A close relationship has been observed between pancreatic islet malfunction and impairment of the ANS in adult rats and mice that were metabolically programmed early in life (Balbo et al 2007, de Oliveira et al 2011Scomparin et al (2009) however, muscarinic and adrenergic receptor of pancreatic b-cells did not show substantial functional differences in the current study.…”

“…b-cells are very sensitive to insults during any phase of life, especially during early and late life, which can result in malfunctions with limited capacity for regeneration or neogenesis (Dumortier et al 2007, Frantz et al 2012, Supale et al 2012. In contrast with other periods of LP intervention such as pregnancy, lactation, and adolescence (Hoet et al 1992, Reusens & Remacle 2006, de Oliveira et al 2011, 2012b, a LP diet during early young adult life does not have a significant effect on the function of the pancreatic islets. Islets isolated from the LP rats exhibit the same glucose-induced insulin secretion magnitude as the NP rats, suggesting that pancreatic b-cells are resistant to LP diet insult early in adulthood, at least up to 150 days of age.…”

“…One group of rats was supplied with a normal-protein (NP; 23% w/w protein) diet and allowed to feed ad libitum (Nuvital, Curitiba, PR, Brazil) throughout the experimental period (the NP group), while the other group of rats (the low-protein (LP) group) received a LP (4% w/w protein) diet containing the same amount of calories as the normal diet from 60 to 90 days of age, as described previously (de Oliveira et al 2011). After 90 days of age, the LP group received a NP diet for another 60 days to allow dietary recovery.…”

Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

“…This value was calculated by determining the difference between the amount of food remaining (Df) and the total amount of food that was previously placed in the cage (Di) and dividing the difference by the number of days and number of rats per cage: [FI (g) = (Df - Di) ⁄ 3⁄ 3] [18]. The area under the curve (AUC) for the food consumption versus time was calculated for the entire observation period (21-90 days).…”

Protein-energy malnutrition at mid-adulthood does not imprint long-term metabolic consequences in male rats

“…In this experimental animal model, these metabolic dysfunctions are implicated in the impairment of autonomic nervous system (ANS) function such as low tonus of vagus nerve and low acetylcholine muscarinic response in pancreatic islets [15,16]. Similar alterations were also observed by others, where ANS disruption was induced by an acute treatment with a low-protein diet in adult rats [17].…”