Influence of maternal high-fat diet on offspring's locomotor activity during anxiety-related behavioral tests: A systematic review.

The aim of this review was to summarize and discuss the impact of a maternal high-fat diet on the locomotor activity of offspring during anxiety-related behavioral tests. A search was performed in the LILACS, Web of Science, SCOPUS and PUMBED databases, using the following inclusion criteria: studies in which rodent dams were submitted to a high-fat diet during gestation and/or lactation and in which the locomotor activity parameters of offspring were evaluated during an anxiety-related test. Twenty-three articles met these criteria and were included. Most studies, 14 out of 23, found that a maternal high-fat diet did not alter offspring locomotor activity. Six articles found that a maternal high-fat diet increased the locomotor activity of offspring, while three found decreased locomotion. This effect may be associated with the initial response to the test and the fact that it was the first day of exposure to the apparatus.

Food consumption and masticatory performance of normal weight, overweight and obese children aged 7 to 12 years old.

Childhood obesity is a significant public health problem. Studies show that obese children are more likely to become obese adults. In an attempt to ascertain the factors associated with childhood obesity, research has shown that this condition is associated with changes in food consumption and masticatory performance. The aim of this study was thus to evaluate food consumption and masticatory performance in normal weight, overweight and obese children aged 7 - 12 years. A cross-sectional study was carried out with 92 children aged 7 - 12 years, of both sexes, from a public school in a Brazilian municipality. The children were divided into the following groups: normal weight (n = 48), overweight (n = 26) and obese (n = 18). Anthropometric parameters, food consumption, food consistency preference, and masticatory performance were evaluated. Pearson's chi-square test was used to compare categorical variables. To compare numerical variables, the one-way ANOVA test was applied. For variables not conforming to a normal distribution, the Kruskal-Wallis test was used. The level of statistical significance was set at p ≤ 0.05. Our results show that the children with obesity consumed fewer fresh foods (median = 3, IQI = 4.00-2.00, p = 0.026), consumed more ultra-processed foods (median = 4, IQI = 4.00-2.00, p = 0.011), performed fewer mastication sequences (median = 2, IQI = 3.00-2.00, p = 0.007), and ate faster (median = 58.50, IQI = 69.00-48.00, p = 0.026) compared to children of normal weight. We conclude that children with obesity exhibit differences in food consumption and masticatory performance compared to children of normal weight.

Repercussions of maternal exposure to high-fat diet on offspring feeding behavior and body composition: a systematic review.

Maternal nutrition is an environmental determinant for offspring growth and development, especially in critical periods. Nutritional imbalances during these phases can promote dysregulations in food intake and feeding preference in offspring, affecting body composition. The aim of this review is to summarize and discuss the effects of maternal high-fat diet (HFD) on offspring feeding behavior and body composition. A search was performed in the PUBMED, SCOPUS, Web of Science, and LILACS databases. Inclusion criteria were studies in rodents whose mothers were submitted to HFD that assessed outcomes of food or caloric intake on offspring and food preference associated or not with body weight or body composition analysis. At the end of the search, 17 articles with the proposed characteristics were included. In these studies, 15 articles manipulated diet during pregnancy and lactation, 1 during pregnancy only, and 1 during lactation only. Maternal exposure to a HFD leads to increased food intake, increased preference for HFDs, and earlier food independence in offspring. The offspring from HFD mothers present low birthweight but become heavier into adulthood. In addition, these animals also exhibited greater fat deposition on white adipose tissue pads. In conclusion, maternal exposure to HFD may compromise parameters in feeding behavior and body composition of offspring, impairing the health from conception until adulthood.

Maternal exposure to high-fat diet modifies anxiety-like/depression-like behaviors and compounds of Serotonergic System in offspring: A preclinical systematic review.

Maternal nutrition affects offspring physiology and behavior including susceptibility to mental health-related states. Perinatal high-fat diet (HFD) consumption has been associated with lower levels of serotonin as well as the development of anxiety-like and depression-like behaviors in offspring. The aim of this systematic review was to investigate the effects of maternal HFD during pregnancy and/or lactation on these behaviors and on some aspects of the serotonergic system. Criteria for eligibility included studies of offspring of rodents and non-human primates exposed to HFD at least during pregnancy and/or lactation, offspring that showed outcomes related to anxiety-like and depression-like behaviors and to the serotonergic system. The searches were realized in the LILACS, Web of Science, Scopus, and PubMed databases. The systematic review protocol was registered on the CAMARADES website. The internal validity was assessed by the SYRCLE risk of bias tool. The Kappa index was used for analyzing agreement among the reviewers. In addition, the PRISMA statement was used to report this systematic review. Sixteen articles were included in this review. Most of which studied HFD prior to mating and during pregnancy and lactation. All studies analyzed outcomes related to emotional behavior; three analyzed outcomes related to serotonin system compounds. Maternal consumption of HFD was found to be associated with an inconsistent pattern of the expression of TPH2 as well as reduced the immunoreactivity of 5-HT in the prefrontal cortex and increased 5-HT1A receptor expression in the dorsal raphe of offspring. An association between an HFD and alterations in emotional behavior was found in most of the studies selected.

Onset and duration of symptoms of loss of smell/taste in patients with COVID-19: A systematic review.

OBJECTIVE: The aim of the study was to conduct a systematic review of the literature to investigate the time of onset and duration of symptoms of loss of smell and taste in patients diagnosed with COVID-19. METHODS: Two independent authors performed a systematic review of the Medline/PubMed, SCOPUS, COCHRANE, Lilacs and Web of Science electronic databases. The time of onset and duration of symptoms were considered primary outcomes. The sex and age of individuals, the geographical location of the study, the prevalence of symptoms, other associated symptoms, associated comorbidities, and the impact on quality of life and eating habits were considered secondary outcomes. RESULTS: Our search generated 17 articles. Many of the studies reported that the onset of anosmia and ageusia occurred 4 to 5 days after the manifestation of other symptoms of the infection and that these symptoms started to disappear after one week, with more significant improvements in the first two weeks. CONCLUSION: The present study concludes that the onset of symptoms of loss of smell and taste, associated with COVID-19, occurs 4 to 5 days after other symptoms, and that these symptoms last from 7 to 14 days. Findings, however, varied and there is therefore a need for further studies to clarify the occurrence of these symptoms. This would help to provide early diagnosis and reduce contagion by the virus.

High-caloric or isocaloric maternal high-fat diets differently affect young-adult offspring behavior in anxiety-related tests and offspring sensitivity to acute fluoxetine.

OBJECTIVE: to evaluate the influence of two maternal high-fat diets with different caloric contents on anxiety-like behavior in young-adult offspring and their sensitivity to acute fluoxetine. METHODS: females Wistar rats were used and divided according to diet received during gestation and lactation: Control (CTR), high-fat/isocaloric (HI) and high-fat/high-caloric (HH). Offspring were subsequently divided into three subgroups according to acute administration of vehicle or fluoxetine (1 or 10 mg/kg). To assess animals' anxiety-like behaviors, three tests were used: open field (OF), elevated plus-maze (EPM) and free-exploratory paradigm (FEP). RESULTS: In OF, HI and HH showed increased hyperactivity- and anxiety-related behaviors, HI being more hyperactive than HH. In response to fluoxetine, HI offspring decreased number of quadrants entered, decreased number of central entries and spent less time in rearing in peripheral areas, while HH offspring showed less time spent in rearing in the OF peripheral area. In EPM test, HI pups spent more time in closed arms than the HH pups. Fluoxetine decreased number of open arms entries for HI offspring and increased percentage of time spent in central area for HH animals. Maternal diet did not influence FEP test, neither HI nor HH presented a response after fluoxetine acute administration. CONCLUSION: Maternal high-fat diets influence offspring anxiety-like behavior in state-anxiety tests but not in trait-anxiety test. Responsiveness to acute fluoxetine depended on maternal diet, dose and which behavioral tests were being evaluated.

Effects of maternal low-protein diet and spontaneous physical activity on the transcription of neurotrophic factors in the placenta and the brains of mothers and offspring rats.

Maternal protein restriction and physical activity can affect the interaction mother-placenta-fetus. This study quantified the gene expression of brain-derived neurotrophic factor (BDNF), neurothrophin 4, tyrosine kinase receptor B (TrkB/NTRK2), insulin-like growth factor (IGF-1), and insulin-like growth factor receptor (IGF-1r) in the different areas of mother's brain (hypothalamus, hippocampus, and cortex), placenta, and fetus' brain of rats. Female Wistar rats (n = 20) were housed in cages containing a running wheel for 4 weeks before gestation. According to the distance spontaneously traveled daily, rats were classified as inactive or active. During gestation, on continued access to the running wheel, active and inactive groups were randomized to receive normoprotein diet (18% protein) or a low-protein (LP) diet (8% protein). At day 20 of gestation, gene expression of neurotrophic factors was analyzed by quantitative polymerase chain reaction in different brain areas and the placenta. Dams submitted to a LP diet during gestation showed upregulation of IGF-1r and BDNF messenger RNA in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, and BDNF, NTRK2, IGF-1 and IGF-1r in the cortex. In the placenta, there was a downregulation of IGF-1. In the brain of pups from mothers on LP diet, IGF-1r and NTRK2 were downregulated. Voluntary physical activity attenuated the effects of LP diet on IGF-1r in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, IGF-1 in the placenta, and NTRK2 in the fetus' brain. In conclusion, both maternal protein restriction and spontaneous physical activity influence the gene expression of BDNF, NTRK2, IGF-1, and IGF-1r, with spontaneous physical activity being able to normalize in part the defects caused by protein restriction during pregnancy.

Neonatal administration of kaempferol does not alter satiety but increases somatic growth and reduces adiposity in offspring of high-fat diet dams.

AIM: The aim of this study was to evaluate the effects of maternal exposure to a high-fat diet associated with neonatal administration of kaempferol on somatic growth, biochemical profile and feeding behavior in offspring. MATERIALS AND METHODS: Wistar rats were distributed according to diet during pregnancy and lactation into Control (C; 3.4 kcal/g; 12% kcal/lipids) or High-fat (HFD; 4.6 kcal/g; 51% kcal/lipids) groups. In the offspring, vehicle (V) or kaempferol (K, 1 mg/kg) were administered from the 8th until the 21st postnatal day (PND). Maternal body weight (BW), caloric intake and adiposity were measured. In the offspring, somatic growth parameters were evaluated on the 7th, 14th, 21st, 25th and 30th PND, except for BW, which was measured from the 8th to the 21st and from the 25th to the 30th PND. Feeding behavior was assessed by food intake and behavioral satiety sequence (BSS) on the 30th PND. The biochemical profile and relative weight of adipose tissue of offspring were also measured. KEY FINDINGS: Dams exposed to HFD showed no difference in body weight and caloric intake but exhibited increased adiposity. Neonatal administration of kaempferol increased body weight after weaning and somatic growth in the offspring of HFD dams. Neonatal kaempferol also reduced adiposity and serum creatinine levels in offspring. Neither maternal diet nor kaempferol altered offspring feeding behavior. SIGNIFICANCE: Neonatal administration of kaempferol promotes increased somatic growth post-weaning, reduces adiposity, and does not alter feeding behavior in offspring from high-fat dams.

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring.

Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother's brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother's brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring's brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring's brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.

A maternal high-fat/high-caloric diet delays reflex ontogeny during lactation but enhances locomotor performance during late adolescence in rats.

Objective: The main goal of the present study was to investigate the effects of two maternal high-fat diets with different energy densities on the somatic growth, reflex ontogeny, and locomotor activity of offspring. Methods: Twenty-nine female Wistar rats (220-250 g) were mated and grouped into three different dietary conditions: control (n = 11, AIN-93G diet, 3.6 kcal/g), high-fat/high-caloric (HH, n = 9, 51% of the calories from fat, 4.62 kcal/g), and high-fat/isocaloric (HI, n = 9, 51% of the calories from fat, 3.64 kcal/g). The fat source was mainly lard. The dietary groups were maintained during gestation and lactation. From postnatal day 1 (PND1) until weaning, the somatic growth, maturation of physical features, and reflex ontogeny of the male pups were evaluated. The locomotor activity was evaluated in an open field at PND8, PND14, PND17, PND21, PND30, PND45, and PND60. Results: HH dams had a lower food intake but no difference in caloric intake or body weight gain. The HH pups had higher body weights, greater tail and body lengths, and an increased axis of the head at weaning. The prediction of ear unfolding, delayed palmar grasp, and cliff avoidance maturation were also observed in the HH offspring. At PND60, the HH pups showed an increased average speed as well as an average potency and kinetic energy in the open field. Conclusion: A high-fat/high-caloric maternal diet increases somatic growth, predicts the maturation of physical features, and delays reflex ontogeny during lactation, and it enhances motor performance during late adolescence. A maternal HI diet does not elicit the same influences on offspring development compared with the HH diet.

Differential effects of maternal high-fat/high-caloric or isocaloric diet on offspring's skeletal muscle phenotype.

Aim This study sought to investigate the effects of two different maternal high-fat diets, during gestation and lactation, on the morphology of the skeletal muscle of the adult offspring rats. METHODS: Female Wistar rats were fed Control (C) or High-fat/high-caloric (HH) or High-fat/isocaloric (HI) diet during gestation and lactation. The somatic growth of the offspring was measured throughout lactation. Glucose and insulin tolerance tests were performed at PND61 and PND65, respectively. At PND70, soleus and extensor digitorum longus (EDL) muscles were removed for myofibrillar ATPase staining analysis. KEY FINDINGS: HH pups were heavier and longer at weaning but presented same body weight at PND70. No difference among groups in glucose or insulin tolerance tests was observed. In the soleus muscle, HH offspring showed increased proportion and size of type 1 fibres and reduced proportion and number with increased size of type 2A fibres. In EDL muscle, there was no difference in proportion and number of fibres. HH and HI animals presented reduced type 1 and 2A fibres size while HH animals presented increased type 2B fibres size, in EDL muscle. SIGNIFICANCE: Maternal HH diet promoted a more oxidative profile in soleus muscle. Though, maternal high-fat/isocaloric diet influenced only fibres size. Glycolytic muscle is more resistant to maternal diet influence. These results emphasize the importance of maternal diet during the critical period of development on muscle morphology of the offspring.

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.

Peripheral and Central Glucocorticoid Signaling Contributes to Positive Energy Balance in Rats.

The obesity epidemic has been the target of several studies to understand its etiology. The pathophysiological processes that take to obesity generally relate to the rupture of energy balance. This imbalance can result from environmental and/or endogenous events. Among the endogenous events, the hypothalamic-pituitary-adrenal axis, which promotes stress response via glucocorticoid activity, is considered a modulator of energy balance. However, it remains controversial whether the increase in plasma levels of glucocorticoids results in a positive or negative energy balance. Furthermore, there are no studies comparing different routes of administration of glucocorticoids in this context. Here, we investigated the effects of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of a specific agonist for glucocorticoid receptors on food intake and energy expenditure in rats. Sixty-day old rats were treated with i.p. or i.c.v. dexamethasone. Food intake and satiety were evaluated, as well as locomotor activity in order to determine energy expenditure. Both i.p. and i.c.v. dexamethasone increased food intake and decreased energy expenditure. Moreover, i.c.v. dexamethasone delayed the onset of satiety. Together, these results confirm that central glucocorticoid signaling promotes a positive energy balance and supports the role of the glucocorticoid system as the underlying cause of psychological stress-induced obesity.

Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis.

Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition.

Neonatal low-protein diet reduces the masticatory efficiency in rats.

Little is known about the effects of undernutrition on the specific muscles and neuronal circuits involved in mastication. The aim of this study was to document the effects of neonatal low-protein diet on masticatory efficiency. Newborn rats whose mothers were fed 17% (nourished (N), n 60) or 8% (undernourished (U), n 56) protein were compared. Their weight was monitored and their masticatory jaw movements were video-recorded. Whole-cell patch-clamp recordings were performed in brainstem slice preparations to investigate the intrinsic membrane properties and N-methyl-d-aspartate-induced bursting characteristics of the rhythmogenic neurons (N, n 43; U, n 39) within the trigeminal main sensory nucleus (NVsnpr). Morphometric analysis (N, n 4; U, n 5) were conducted on masseteric muscles serial cross-sections. Our results showed that undernourished animals had lower numbers of masticatory sequences (P=0·049) and cycles (P=0·045) and slower chewing frequencies (P=0·004) (N, n 32; U, n 28). Undernutrition reduced body weight but had little effect on many basic NVsnpr neuronal electrophysiological parameters. It did, however, affect sag potentials (P<0·001) and rebound firing (P=0·005) that influence firing pattern. Undernutrition delayed the appearance of bursting and reduced the propensity to burst (P=0·002), as well as the bursting frequency (P=0·032). Undernourished animals showed increased and reduced proportions of fibre type IIA (P<0·0001) and IIB (P<0·0001), respectively. In addition, their fibre areas (IIA, P<0·001; IIB, P<0·001) and perimeters (IIA, P<0·001; IIB, P<0·001) were smaller. The changes observed at the behavioural, neuronal and muscular levels suggest that undernutrition reduces chewing efficiency by slowing, weakening and delaying maturation of the masticatory muscles and the associated neuronal circuitry.

Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition.

Impaired hypothalamic mTOR activation in the adult rat offspring born to mothers fed a low-protein diet.

Several epidemiological and experimental studies have clearly established that maternal malnutrition induces a high risk of developing obesity and related metabolic diseases in the offspring. To determine if altered nutrient sensing might underlie this enhanced disease susceptibility, here we examined the effects of perinatal protein restriction on the activation of the nutrient sensor mTOR in response to acute variations in the nutritional status of the organism. Female Wistar rats were fed isocaloric diets containing either 17% protein (control) or 8% protein (PR) throughout pregnancy and lactation. At weaning offspring received standard chow and at 4 months of age the effects of fasting or fasting plus re-feeding on the phosphorylation levels of mTOR and its downstream target S6 ribosomal protein (rpS6) in the hypothalamus were assessed by immuno-fluorescence and western blot. Under ad libitum feeding conditions, PR rats exhibited decreased mTOR and rpS6 phosphorylation in the arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei. Moreover, the phosphorylation of mTOR and rpS6 in these hypothalamic nuclei decreased with fasting in control but not in PR animals. Conversely, PR animals exhibited enhanced number of pmTOR imunostained cells in the paraventricular nucleus (PVN) and fasting decreased the activation of mTOR in the PVN of malnourished but not of control rats. These alterations occurred at a developmental stage at which perinatally-undernourished animals do not show yet obesity or glucose intolerance. Collectively, our observations suggest that altered hypothalamic nutrient sensing in response to an inadequate foetal and neonatal energetic environment is one of the basic mechanisms of the developmental programming of metabolic disorders and might play a causing role in the development of the metabolic syndrome induced by malnutrition during early life.

Long-lasting effect of perinatal exposure to L-tryptophan on circadian clock of primary cell lines established from male offspring born from mothers fed on dietary protein restriction.

BACKGROUND AIMS: Maternal undernutrition programs metabolic adaptations which are ultimately detrimental to adult. L-tryptophan supplementation was given to manipulate the long-term sequelae of early-life programming by undernutrition and explore whether cultured cells retain circadian clock dysregulation. METHODS: Male rat pups from mothers fed on low protein (8%, LP) or control (18%, CP) diet were given, one hour before light off, an oral bolus of L-tryptophan (125 mg/kg) between Day-12 and Day-21 of age. Body weight, food intake, blood glucose along with the capacity of colonization of primary cells from biopsies were measured during the young (45-55 days) and adult (110-130 days) phases. Circadian clock oscillations were re-induced by a serum shock over 30 hours on near-confluent cell monolayers to follow PERIOD1 and CLOCK proteins by Fluorescent Linked ImmunoSorbent Assay (FLISA) and period1 and bmal1 mRNA by RT-PCR. Cell survival in amino acid-free conditions were used to measure circadian expression of MAP-LC3B, MAP-LC3B-FP and Survivin. RESULTS: Tryptophan supplementation did not alter body weight gain nor feeding pattern. By three-way ANOVA of blood glucose, sampling time was found significant during all phases. A significant interaction between daily bolus (Tryptophan, saline) and diets (LP, CP) were found during young (p = 0.0291) and adult (p = 0.0285) phases. In adult phase, the capacity of colonization at seeding of primary cells was twice lower for LP rats. By three-way ANOVA of PERIOD1 perinuclear/nuclear immunoreactivity during young phase, we found a significant effect of diets (p = 0.049), daily bolus (p<0.0001) and synchronizer hours (p = 0.0002). All factors were significantly interacting (p = 0.0148). MAP-LC3B, MAP-LC3B-FP and Survivin were altered according to diets in young phase. CONCLUSIONS: Sequelae of early-life undernutrition and the effects of L-tryptophan supplementation can be monitored non-invasively by circadian sampling of blood D-glucose and on the expression of PERIOD1 protein in established primary cell lines.