Maternal low-protein diet reduces skeletal muscle protein synthesis and mass via Akt-mTOR pathway in adult rats.

Several studies have demonstrated that a maternal low-protein diet induces long-term metabolic disorders, but the involved mechanisms are unclear. This study investigated the molecular effects of a low-protein diet during pregnancy and lactation on glucose and protein metabolism in soleus muscle isolated from adult male rats. Female rats were fed either a normal protein diet or low-protein diet during gestation and lactation. After weaning, all pups were fed a normal protein diet until the 210th day postpartum. In the 7th month of life, mass, contractile function, protein and glucose metabolism, and the Akt-mTOR pathway were measured in the soleus muscles of male pups. Dry weight and contractile function of soleus muscle in the low-protein diet group rats were found to be lower compared to the control group. Lipid synthesis was evaluated by measuring palmitate incorporation in white adipose tissue. Palmitate incorporation was higher in the white adipose tissue of the low-protein diet group. When incubated soleus muscles were stimulated with insulin, protein synthesis, total amino acid incorporation and free amino acid content, glucose incorporation and uptake, and glycogen synthesis were found to be reduced in low-protein diet group rats. Fasting glycemia was higher in the low-protein diet group. These metabolic changes were associated with a decrease in Akt and GSK-3ß signaling responses to insulin and a reduction in RPS6 in the absence of the hormone. There was also notably lower expression of Akt in the isolated soleus muscle of low-protein diet group rats. This study is the first to demonstrate how maternal diet restriction can reduce skeletal muscle protein and mass by downregulating the Akt-mTOR pathway in adulthood.

Maternal voluntary physical activity attenuates delayed neurodevelopment in malnourished rats.

NEW FINDINGS: What is the central question of this study? In the present study, a reproducible model of maternal voluntary physical activity was developed to evaluate the adaptive response of physical activity by attenuating the effects of maternal undernutrition on physical features, reflex ontogeny and growth trajectory of offspring during development. What is the main finding and its importance? Maternal physical activity may induce neuronal maturation of sensorimotor connections impacting on the patterns of locomotor activity in malnourished offspring. Thus, physical activity should be considered as a therapeutic means of countering the effects of maternal undernutrition, by providing a useful strategy for enhancing the neuronal activity of children born to mothers who experience a restricted diet during pregnancy. This study evaluated the effects of maternal voluntary physical activity during pregnancy and lactation on somatic growth (SG), reflex ontogeny (RO) and locomotor activity (LA) of rats whose mothers were protein restricted. Virgin female Wistar rats were divided into the following six groups: control, normal protein (C-NP, n = 4); control, low protein (C-LP, n = 4); inactive, normal protein (I-NP, n = 8); inactive, low protein (I-LP, n = 7); very active, normal protein (VA-NP, n = 8); and very active, low protein (VA-LP, n = 6). Voluntary physical activity was recorded daily in dams. The LP groups were fed an 8% casein diet, whereas control groups were fed a 17% casein diet during pregnancy and lactation. Offspring were evaluated in terms of SG (body weight and length, latero-lateral skull axis and anteroposterior head axis) and RO (palmar grasp, righting, free-fall righting, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing). The LA was evaluated at 23, 45 and 60 days old in the open field. Voluntary physical activity was reduced during pregnancy and lactation independent of the maternal diet. Pups from LP dams showed delayed SG, reflex maturation and patterns of LA when compared with control pups. The C-LP and I-LP pups showed a delayed SG, RO and LA. Pups from VA-LP mothers showed no delay in SG and RO and presented a faster development of patterns of LA. Maternal voluntary physical activity attenuated the effects of LP diet on indicators of neurodevelopment and patterns of LA of offspring.

Programmed changes in the adult rat offspring caused by maternal protein restriction during gestation and lactation are attenuated by maternal moderate-low physical training.

The effects of maternal moderate-low physical training on postnatal development, glucose homeostasis and leptin concentration in adult offspring subjected to a low-protein diet during the perinatal period were investigated. Male Wistar rats (aged 150 d old) were divided into four groups according to maternal group: untrained (NTp, n 8); trained (Tp, n 8); untrained with a low-protein diet (NT+LPp, n 8); trained with a low-protein diet (T+LPp, n 8). The trained mothers were subjected to a protocol of moderate physical training over a period of 4 weeks (treadmill, 5 d/week, 60 min/d, at 65 % VO(2max)) before mating. At pregnancy, the intensity and duration of exercise was progressively reduced (50-20 min/d, at 65-30 % VO(2max)). The low-protein diet groups received an 8 % casein diet, and their peers received a 17 % casein diet during gestation and lactation. The pups' birth weight and somatic growth were recorded weekly up to the 150th day. Fasting blood glucose, cholesterol, serum leptin concentration, glucose and insulin tolerance tests were evaluated. The Tp animals showed no changes in somatic and biochemical parameters, while the NT+LPp group showed a greater abdominal circumference, hyperglycaemia, hypercholesterolaemia, glucose intolerance and lower plasma leptin. In the T+LPp animals, all of those alterations were reversed except for plasma leptin concentration. In conclusion, the effects of a perinatal low-protein diet on growth and development, glucose homeostasis and serum leptin concentration in the offspring were attenuated in pups from trained mothers.

Maternal moderate physical training during pregnancy attenuates the effects of a low-protein diet on the impaired secretion of insulin in rats: potential role for compensation of insulin resistance and preventing gestational diabetes mellitus.

The effects of pregestational and gestational low-to-moderate physical training on insulin secretion in undernourished mothers were evaluated. Virgin female Wistar rats were divided into four groups as follows: control (C, n = 5); trained (T, n = 5); low-protein diet (LP, n = 5); trained with a low-protein diet (T + LP, n = 5). Trained rats ran on a treadmill over a period of 4 weeks before mate (5 days week⁻¹ and 60 min day⁻¹, at 65% of VO(2max)). At pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8% casein diet, and controls were provided with a 17% casein diet. At third day after delivery, mothers and pups were killed and islets were isolated by collagenase digestion of pancreas and incubated for a further 1 h with medium containing 5.6 or 16.7 mM glucose. T mothers showed increased insulin secretion by isolated islets incubated with 16.7 mM glucose, whereas LP group showed reduced secretion of insulin by isolated islets when compared with both C and LP + T groups. Physical training before and during pregnancy attenuated the effects of a low-protein diet on the secretion of insulin, suggesting a potential role for compensation of insulin resistance and preventing gestational diabetes mellitus.

Desnutrição perinatal e o controle hipotalâmico do comportamento alimentar e do metabolismo do músculo esquelético / Perinatal undernutrition and hypothalamic control of food intake and energy metabolism in the skeletal muscle

A deficiência de nutrientes durante os períodos críticos do desenvolvimento tem sido associada com maior risco para desenvolver obesidade e diabetes Mellitus na vida adulta. Um dos mecanismos propostos refere-se à regulação do comportamento alimentar e às alterações do metabolismo energético do músculo esquelético. Recentemente, tem sido proposta a existência de uma comunicação entre o hipotálamo e o músculo esquelético a partir de sinais autonômicos que podem explicar as repercussões da desnutrição perinatal. Assim, esta revisão tem como objetivo discutir as repercussões da desnutrição perinatal sobre o comportamento alimentar e o metabolismo energético muscular e a comunicação existente entre o hipotálamo e o músculo via sinais adrenérgicos. Foram utilizadas as bases de dados MedLine/PubMed, Lilacs e Bireme, com publicações entre 2000 e 2011. Os termos de indexação utilizados foram: feeding behavior, energy metabolism, protein malnutrition, developmental plasticity, skeletal muscle e autonomic nervous system. Concluiu-se que a desnutrição perinatal pode atuar no controle hipotalâmico do comportamento alimentar e no metabolismo energético muscular, e a comunicação hipotálamo-músculo pode favorecer o desenvolvimento de obesidade e comorbidades durante o desenvolvimento.

Undernutrition during the critical period of development has been associated with susceptibility to obesity and diabetes Mellitus in adulthood. One of the underlying mechanisms can be related with the relationship between the food intake and the metabolism of skeletal muscle. A communication between the hypothalamus and skeletal muscle has been recently proposed, which can explain the repercussion of perinatal undernutrition. Thus, this review aims mainly to discuss the repercussions of perinatal undernutrition on food intake and skeletal muscle metabolism by adrenergic signals. Articles published from 2000 to 2011 were searched in the Medline/Pubmed, Lilacs and Bireme databases using the following keywords: feeding behavior, energy metabolism, protein malnutrition, developmental plasticity, skeletal muscle and autonomic nervous system. In conclusion, perinatal undernutrition can alter the hypothalamic control of food intake and skeletal muscle metabolism. Additionally, communication between the hypothalamus and skeletal muscle can promote the development of obesity and associated diseases.

Efeitos do treinamento físico durante a gestação sobre a evolução ponderal, glicemia e colesterolemia de ratos adultos submetidos à desnutrição perinatal / Effects of physical training during pregnancy on body weight gain, blood glucose and cholesterol in adult rats submitted to perinatal undernutrition

A incompatibilidade entre a desnutrição perinatal e uma nutrição adequada durante o desenvolvimento aumenta o risco de aparecimento precoce de doenças não transmissíveis na vida adulta. Todavia, acredita-se que a atividade física materna possa atenuar estas consequências. O presente estudo teve como objetivo avaliar os efeitos do treinamento físico durante a gestação na evolução ponderal, circunferência abdominal, glicemia e colesterolemia de filhotes adultos submetidos à desnutrição perinatal. Ratas Wistar (n = 12) foram divididas em quatro grupos: controle (C, n = 3), treinada (T, n = 3), desnutrida (D, n = 3) e treinada desnutrida (T+D, n = 3). Durante a gestação e lactação, os grupos D e T+D receberam dieta baixa em proteína (8% caseína) e os grupos C e T receberam dieta normoproteica (caseína a 17%). O protocolo de treinamento físico moderado foi realizado em esteira ergométrica (cinco dias/semana, 60 min/dia, a 65% do VO2max) e iniciou quatro semanas antes da gestação. Na gestação, a duração e a intensidade do treinamento foram reduzidas (cinco dias/semana, 20 min/dia, a 30% do VO2max) até o 19º dia pré-natal. Após o desmame, os filhotes (C F = 9, T F = 9, D F = 7, T+D F = 9) receberam dieta padrão de biotério e foram avaliados aos 270 dias de idade. A circunferência abdominal (CA) foi avaliada relativa ao peso corporal. Para avaliação da glicemia e colesterolemia foi utilizado o método enzimático colorimétrico da glicose-oxidase/peroxidase e da colesterol-oxidase, respectivamente. Ratos do grupo D F apresentaram um maior ganho de peso corporal ao longo do crescimento, maiores valores de CA, glicemia e colesterolemia quando comparados ao grupo C F. Para o grupo T+D F, o ganho de peso foi atenuado, e a CA, a glicemia e a colesterolemia foram normalizadas (p < 0,05). Esses resultados demonstram que o treinamento físico durante a gestação atenua os efeitos da desnutrição perinatal sobre alguns indicadores murinométricos e bioquímicos nos filhotes adultos.

The incompatibility of perinatal undernutrition and adequate nutrition during development increases the risk of early onset of non-communicable diseases in adulthood. However, it has been considered that maternal physical activity may attenuate these effects. This study aimed to evaluate the effects of physical training during pregnancy on body weight gain, waist circumference, glycaemia and cholesterolemia in adult offspring submitted to perinatal undernutrition. Female Wistar rats (n = 12) were divided into four groups: control (C, n = 3), trained (T, n = 3), undernourished (D, n = 3) undernourished and trained (T+D, n = 3). During gestation and lactation, D and T+D groups were fed a low protein diet (8% casein) and C and T groups fed a normal protein diet (17% casein). The protocol of moderate physical training was performed on a treadmill (5 days/week, 60 min/day, at 65% of VO2max) and began 4 weeks before pregnancy. At pregnancy, the duration and intensity of training were reduced (5 days/week, 20 min/day, at 30% VO2max) until the 19th prenatal day. At weaning, male pups (CP = 9, TP = 9, DP = 7, T+DP = 9) received standard diet and evaluations took place at 270 days old. Abdominal circumference (AC) was evaluated in relation to body weight. Enzymatic colorimetric method glucose-oxidase/peroxidase and cholesterol-oxidase was used to evaluate fasting glycaemia and cholesterolemia, respectively. Rats from DP group showed high body weight gain during growth, values of CA, glycaemia and cholesterolemia when compared to CP. Concerning the T+DP group,body weight gain was attenuated, and the CA, glycaemia and cholesterolemia were normalized (p<0.05). These results demonstrate that physical training during pregnancy reduces the effects of perinatal undernutrition on some murinometric and biochemical indicators of adult offspring.

Moderate physical training attenuates muscle-specific effects on fibre type composition in adult rats submitted to a perinatal maternal low-protein diet.

AIM: To verify whether moderate physical training affects the muscle fibre composition of adult rats subjected to a low protein diet during the perinatal period. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during gestation and lactation: control (17% casein, C) and low-protein (8% casein, LP). On postnatal day 60, half of each group was submitted to moderate physical training (8 weeks, 5 days/week(-1), 60 min/day(-1), at 70% of VO(2max), T) or not. After the physical training period, soleus and extensor digitorum longus (EDL) muscles were removed. Myofibrillar ATPase staining was used to classify muscle fibres as type I, IIa, IIb, and intermediate. RESULTS: In the EDL muscle, LP rats showed no changes in the fibre type proportion. Both the C + T and LP + T groups showed a higher percentage of fibres of type IIa, and a lower proportion of fibres of type IIb. In the soleus muscle, LP animals showed a reduction in the proportion of fibre types I and intermediate. C + T rats showed an increase in the fibre type I and IIa. In the LP + T rats, the proportions of the fibre types remained similar to control rats. CONCLUSIONS: Moderate physical training acts as a positive environmental stimulus that reverts the effects of a perinatal low-protein diet on the proportion of fibre types in skeletal muscle.

Maternal low-protein diet-induced delayed reflex ontogeny is attenuated by moderate physical training during gestation in rats.

We evaluated the effects of moderate- to low-intensity physical training during gestation on reflex ontogeny in neonate rats whose mothers were undernourished. Virgin female Wistar rats were divided into four groups as follows: untrained (NT, n 7); trained (T, n 7); untrained with a low-protein diet (NT+LP, n 7); trained with a low-protein diet (T+LP, n 4). Trained rats were subjected to a protocol of moderate physical training on a treadmill over a period of 4 weeks (5 d/week and 60 min/d, at 65 % of VO2max). After confirming the pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8 % casein diet, and controls were provided with a 17 % casein diet. Their respective offspring were evaluated (during the 10th-17th days of postnatal life) in terms of physical feature maturation, somatic growth and reflex ontogeny. Pups born to mothers provided with the low-protein diet during gestation and lactation showed delayed physical feature and reflex maturation and a deficit in somatic growth when compared with controls. However, most of these deficiencies were attenuated in pups of undernourished mothers undergoing training. In conclusion, physical training during gestation attenuates the effects of perinatal undernutrition on some patterns of maturation in the central nervous system during development.