Moderate aerobic training counterbalances the deleterious effect of undernutrition on oxidative balance and mitochondrial markers.

The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Effect of Creatine Supplementation on Body Composition and Malnutrition-Inflammation Score in Hemodialysis Patients: An Exploratory 1-Year, Balanced, Double-Blind Design.

Hemodialysis has a detrimental effect on fat-free mass (FFM) and muscle strength over time. Thus, we aimed to evaluate the effect of creatine supplementation on the body composition and Malnutrition-Inflammation Score (MIS) in patients with chronic kidney disease (CKD) undergoing hemodialysis. An exploratory 1-year balanced, placebo-controlled, and double-blind design was conducted with hemodialysis patients (≥18 years). The creatine group (CG) received 5 g of creatine monohydrate and 5 g of maltodextrin per day and the placebo group (PG) received 10 g of maltodextrin per day. MIS and body composition were analyzed at three time points: pre, intermediate (after 6 months), and post (after 12 months). After 6 months, 60% of patients on creatine experienced an increase in FFM compared to a 36.8% increase for those on placebo. Moreover, 65% of patients on creatine increased their skeletal muscle mass index (SMMI) compared to only 15.8% for those on placebo. Creatine increased intracellular water (ICW) in 60% of patients. MIS did not change after the intervention. In the CG, there was an increase in body weight (p = 0.018), FFM (p = 0.010), SMMI (p = 0.022). CG also increased total body water (pre 35.4 L, post 36.1 L; p = 0.008), mainly due to ICW (pre 20.2 L, intermediate 20.7 L, post 21.0 L; p = 0.016). Long-term creatine supplementation in hemodialysis patients did not attenuate the MIS, but enhanced FFM and SMMI, which was likely triggered by an increase in ICW.

Reduced protein intake and aging affects the sustainment of hematopoiesis by impairing bone marrow mesenchymal stem cells.

Protein malnourishment (PM) is common among the elderly, but how aging and PM impact hematopoiesis is not fully understood. This study aimed to assess how aging and PM affect the hematopoietic regulatory function of bone marrow (BM) mesenchymal stem cells (MSCs). Young and aged male C57BL/6J mice were fed with normoproteic or hypoproteic diets and had their nutritional, biochemical, and hematological parameters evaluated. BM MSCs were characterized and had their secretome, gene expression, autophagy, reactive oxygen species production (ROS), and DNA double-stranded breaks evaluated. The modulation of hematopoiesis by MSCs was assayed using in vitro and in vivo models. Lastly, BM invasiveness and mice survival were evaluated after being challenged with leukemic cells of the C1498 cell line. Aging and PM alter biochemical parameters, changing the peripheral blood and BM immunophenotype. MSC autophagy was affected by aging and the frequencies for ROS and DNA double-stranded breaks. Regarding the MSCs' secretome, PM and aging affected CXCL12, IL-6, and IL-11 production. Aging and PM up-regulated Akt1 and PPAR-γ while down-regulating Cdh2 and Angpt-1 in MSCs. Aged MSCs increased C1498 cell proliferation while reducing their colony-forming potential. PM and aging lowered mice survival, and malnourishment accumulated C1498 cells at the BM. Finally, aged and/or PM MSCs up-regulated Sox2, Nanog, Pou5f1, and Akt1 expression while down-regulating Cdkn1a in C1498 cells. Together, aging and PM can induce cell-intrinsic shifts in BM MSCs, creating an environment that alters the regulation of hematopoietic populations and favoring the development of malignant cells.

Environmental enrichment changes the effects of prenatal and postnatal undernutrition on memory, anxiety traits, Bdnf and TrkB expression in the hippocampus of male adult rats.

Environmental factors such as undernutrition and environmental enrichment can promote changes in the molecular and behavioural mechanisms related to cognition. Herein, we investigated the effect of enriched environment stimulation in rats that were malnourished in the pre- and postnatal periods on changes in the gene expression of brain-derived neurotrophic factor and its receptor in the hippocampus, as well as on anxiety traits and memory. Early undernutrition promoted weight reduction, increased the risk analysis, reduced permanence in the open arm of the elevated plus-maze and induced a reduction in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B. However, exposure to an enriched environment from 30 to 90 days' old maintained the malnourished phenotype, leading to weight reduction in the control group. In addition, the enriched environment did not alter the risk assessment in the undernourished group, but it did increase the frequency of labyrinth entries. Sixty-day exposure to the enriched environment resulted in a reversal in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus of malnourished rats and favoured of long-term memory in the object recognition test in the open-field. These results suggest that an enriched environment may have a protective effect in adult life by inducing changes in long-term memory and anxiety traits in animals that were undernourished in early life. Furthermore, reversing these effects of undernutrition involves mechanisms linked to the molecular signalling of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus.

Oxidative stress associated with spatial memory impairment and social olfactory deterioration in female mice reveals premature aging aroused by perinatal protein malnutrition.

Early-life adversity, like perinatal protein malnutrition, increases the vulnerability to develop long-term alterations in brain structures and function. This study aimed to determine whether perinatal protein malnutrition predisposes to premature aging in a murine model and to assess the cellular and molecular mechanisms involved. To this end, mouse dams were fed either with a normal (NP, casein 20%) or a low-protein diet (LP, casein 8%) during gestation and lactation. Female offspring were evaluated at 2, 7 and 12 months of age. Positron emission tomography analysis showed alterations in the hippocampal CA3 region and the accessory olfactory bulb of LP mice during aging. Protein malnutrition impaired spatial memory, coinciding with higher levels of reactive oxygen species in the hippocampus and sirt7 upregulation. Protein malnutrition also led to higher senescence-associated ß-galactosidase activity and p21 expression. LP-12-month-old mice showed a higher number of newborn neurons that did not complete the maturation process. The social-odor discrimination in LP mice was impaired along life. In the olfactory bulb of LP mice, the senescence marker p21 was upregulated, coinciding with a downregulation of Sirt2 and Sirt7. Also, LP-12-month-old mice showed a downregulation of catalase and glutathione peroxidase, and LP-2-month-old mice showed a higher number of newborn neurons in the subventricular zone, which then returned to normal values. Our results show that perinatal protein malnutrition causes long-term impairment in cognitive and olfactory skills through an accelerated senescence phenotype accompanied by an increase in oxidative stress and altered sirtuin expression in the hippocampus and olfactory bulb.

Malnutrition and Biomarkers: A Journey through Extracellular Vesicles.

Extracellular vesicles (EVs) have been identified as active components in cellular communication, which are easily altered both morphologically and chemically by the cellular environment and metabolic state of the body. Due to this sensitivity to the conditions of the cellular microenvironment, EVs have been found to be associated with disease conditions, including those associated with obesity and undernutrition. The sensitivity that EVs show to changes in the cellular microenvironment could be a reflection of early cellular alterations related to conditions of malnutrition, which could eventually be used in the routine monitoring and control of diseases or complications associated with it. However, little is known about the influence of malnutrition alone; that is, without the influence of additional diseases on the heterogeneity and specific content of EVs. To date, studies in "apparently healthy" obese patients show that there are changes in the size, quantity, and content of EVs, as well as correlations with some metabolic parameters (glucose, insulin, and serum lipids) in comparison with non-obese individuals. In light of these changes, a direct participation of EVs in the development of metabolic and cardiovascular complications in obese subjects is thought to exist. However, the mechanisms through which this process might occur are not yet fully understood. The evidence on EVs in conditions of undernutrition is limited, but it suggests that EVs play a role in the maintenance of homeostasis and muscle repair. A better understanding of how EVs participate in or promote cellular signaling in malnutrition conditions could help in the development of new strategies to treat them and their comorbidities.

Nutritional stress timing differentially programs cognitive abilities in young adult male mice.

Objectives: The impact of chronic exposure to environmental adversities on brain regions involved in cognition and mental health depends on whether it occurs during the perinatal period, childhood, adolescence or adulthood. The effects of these adversities on the brain and behavior arise as a function of the timing of the exposure and their co-occurrence with the development of specific regions. Here we aimed to explore the behavioral phenotypes derived from two nutritional stress paradigms which differed in the timing of exposure: a low-protein perinatal diet during gestation and lactation and a low-protein diet during adolescence.Methods: Locomotor and exploratory activity, recognition memory and aversive memory were measured in CF-1 8-week-old male mice subjected to perinatal malnutrition (LP-P) or adolescent malnutrition (LP-A), and their respective controls with normal protein diet (NP-P and NP-A).Results: By using the open field test, we found that LP-P and LP-A mice showed reduced exploratory activity compared to controls, but no alterations in their locomotor activity. Recognition memory was impaired only in LP-P mice. Interestingly, aversive memory was not altered in LP-P mice but was enhanced in LP-A mice. Considering the stress-inoculation theory, we hypothesized that protein malnutrition during adolescence represents a challenging but still moderate stressful environment, which promotes active coping in face of later adversity.Conclusion: Our results indicate that while perinatal malnutrition impairs recognition memory, adolescent malnutrition enhances aversive memory, showing dissimilar adaptive responses.

Perinatal protein malnutrition induces the emergence of enduring effects and age-related impairment behaviors, increasing the death risk in a mouse model.

BACKGROUND: Early-life adversity impacts on the offspring's brain development and is associated with a higher risk of developing age-associated diseases. In particular, perinatal protein malnutrition appears to be one of the most critical nutritional deficiencies affecting the individual's health and survival, but little is known about its effects on the persistence of behavioral alterations throughout life. Thus, the aim of the present study was to investigate how perinatal protein malnutrition impacts on age-related changes in the neuromuscular, cognitive and behavioral functions throughout life in a mouse model. METHODS: One group of CF-1 dams received a normal-protein diet (NP: 20% casein) during gestation and lactation, whereas another group received a low-protein diet (LP: 10% casein). The offspring of both groups were analyzed by means of several behavioral tests at four different ages (young: 6-10 weeks old, mature: 22-26 weeks old, middle age: 39-43 weeks old, and old: 55-59 weeks old). RESULTS: Regarding neuromuscular functions, LP mice showed an early deterioration in muscular strength and a reduction in the body weight throughout life. Regarding behavior, while NP mice showed an age-related reduction of exploratory behavior, LP mice showed a constantly low level of this behavior, as well as high anxiety-like behavior, which remained at high levels throughout life. Regarding cognitive functions, LP mice showed deteriorated working memory at middle age. Finally, LP mice died 3.4 times earlier than NP mice. Analysis of the sex-related vulnerability showed that females and males were equally affected by perinatal protein malnutrition throughout life. CONCLUSION: Our results demonstrate that perinatal protein malnutrition induces enduring and age-related impairment behaviors, which culminate in higher death risk, affecting males and females equally.

Does the enriched environment alter memory capacity in malnourished rats by modulating BDNF expression?

Environmental factors interfere in the neural plasticity processes. Among these, malnutrition in the early stages of life stands out as one of the main non-genetic factors that can interfere in the morphofunctional development of the nervous system. Furthermore, sensory stimulation from enriched environments (EE) also interferes with neural development. These two factors can modify areas related to memory and learning as the hippocampus, through mechanisms related to the gene expression of brain-derived neurotrophic factor (BDNF). The BDNF may interfere in synaptic plasticity processes, such as memory. In addition, these changes in early life may affect the functioning of the hippocampus during adulthood through mechanisms mediated by BDNF. Therefore, this study aims to conduct a literature review on the effects of early malnutrition on memory and the relationship between the underlying mechanisms of EE, BDNF gene expression, and memory. In addition, there are studies that demonstrate the effect of EE reversal on exposure to changes in the functioning of hippocampal malnutrition in adult rats that were prematurely malnourished. Thereby, evidence from the scientific literature suggests that the mechanisms of synaptic plasticity in the hippocampus of adult animals are influenced by malnutrition and EE, and these alterations may involve the participation of BDNF as a key regulator in memory processes in the adult animal hippocampus.

Soporte nutricional especializado en un paciente con úlceras por presión: un informe de caso / Specialized nutritional support in a patient with pressure ulcers: a case report

Las úlceras por presión son lesiones de la piel y/o del tejido subyacente. El soporte nutricional adecuado constituye parte del tratamiento de estas lesiones. El objetivo de este reporte es demostrar la eficacia del soporte nutricional como factor coadyuvante en la recuperación de éstas. Paciente masculino de 29 años de edad que ingresó al hospital con diagnóstico de neuroinfección. Durante su estadía desarrolló una úlcera en la región sacra. Fue tratado con nutrición enteral por sonda nasoentérica que incluyó dieta y soporte nutricional hiperproteicos enriquecido con glutamina y arginina; posteriormente se brindó colágeno hidrolizado. A los 36 días tras la aparición de la úlcera, ésta es recuperada. Luego de 4 meses, el paciente fue dado de alta. La intervención nutricional fue crucial en la recuperación de la úlcera. Se enfatiza la necesidad de prevenirlas a través de un monitoreo oportuno y adecuado.

Pressure ulcers are injuries to the skin and / or the underlying tissue. Opportune nutritional support is part of the treatment of these injuries. This report aims to demonstrate the efficacy of nutritional support as a contributing factor in this ulcer recovery. A 29-year-old male patient was admitted to the hospital with a diagnosis of neuroinfection. During his stay, he developed a pressure ulcer in the sacral region. He was treated with enteral nutrition via a nasoenteric tube that included a hyperprotein diet and nutritional support enriched with glutamine and arginine; subsequently, hydrolyzed collagen was provided. Thirty-six days after the development of the pressure ulcer, it has recovered. After four months, the patient was discharged. The nutritional intervention was crucial in the recovery of UPP. The need to prevent this type of ulcers through timely and adequate monitoring is emphasized.

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats.

BACKGROUND/AIMS: Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. METHODS: Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. RESULTS: M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. CONCLUSION: The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.

Calorie restriction during gestation affects ovarian reserve in offspring in the mouse.

The aim of this study was to investigate the effect of calorie restriction (CR) during pregnancy in mice on metabolism and ovarian function in the offspring. Pregnant female mice were divided into two groups, a control group and a CR group (n=7 in each). Mice in the CR group were fed 50% of the amount consumed by control females from Day 10 of gestation until delivery. After weaning, the offspring received diet ad libitum until 3 months of age, when ovaries were collected. Ovaries were serially cut and every sixth section was used for follicle counting. Female offspring from CR dams tended to have increased bodyweight compared with offspring from control females (P=0.08). Interestingly, fewer primordial follicles (60% reduction; P=0.001), transitional follicles (P=0.0006) and total follicles (P=0.006) were observed in offspring from CR mothers. The number of primary, secondary and tertiary follicles did not differ between the groups (P>0.05). The CR offspring had fewer DNA double-strand breaks in primary follicle oocytes (P=0.03). In summary, CR during the second half of gestation decreased primordial ovarian follicle reserve in female offspring. These findings suggest that undernutrition during the second half of gestation may decrease the reproductive lifespan of female offspring.

Identification of potential molecular pathways involved in prostate carcinogenesis in offspring exposed to maternal malnutrition.

The developmental origins of health and disease concept links adult diseases with early-life exposure to inappropriate environmental conditions. Intrauterine and postnatal malnutrition may lead to an increased incidence of type 2 diabetes, obesity, and cardiovascular diseases. Maternal malnutrition (MM) has also been associated with prostate carcinogenesis. However, the molecular mechanisms associated with this condition remain poorly understood. Using a proteomic analysis, we demonstrated that MM changed the levels of proteins associated with growth factors, estrogen signaling, detoxification, and energy metabolism in the prostate of both young and old rats. These animals also showed increased levels of molecular markers of endoplasmic reticulum function and histones. We further performed an in silico analysis that identified commonly deregulated proteins in the ventral prostate of old rats submitted to MM with a mouse model and patients with prostate cancer. In conclusion, our results demonstrated that estrogenic signaling pathways, endoplasmic reticulum functions, energy metabolism, and molecular sensors of protein folding and Ca2+ homeostasis, besides histone, and RAS-GTPase family appear to be involved in this process. Knowledge of these factors may raise discussions regarding the role of maternal dietary intervention as a public policy for the lifelong prevention of chronic diseases.

Malnourishment during early lactation disrupts the ontogenetic distribution of the CART and α-MSH anorexigenic molecules in the arcuate/paraventricular pathway and lateral hypothalamus in male rats.

Developmental malnourishment impacts the energetic metabolism control throughout life. In rat offspring, a 0% protein diet during the first 10 days of lactation results in leptin resistance and in alterations in: feeding behavior, serum leptin and neuropeptide Y (NPY) levels in the hypothalamic arcuate nucleus (ARC)/paraventricular (PVN) pathway. Here, the distributions of alpha-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine regulated transcript (CART), anorexigenic molecules, were immunohistochemically assessed in the ARC, PVN and lateral hypothalamus (LH) nuclei. Rat dams were subjected to one of the following diet protocols from postnatal day (P) 1-10: 1) Protein-free (PFG, 0% protein chow); 2) Pair-fed (UFG, normoprotein chow); 3) Control group (CG, normoprotein chow). PFG, UFG and CG male offspring were analyzed at different time points, from P5 to P180. In the ARC, PFG α-MSH and CART were increased from P10 to P45 when compared to CG and UFG. In the PVN, α-MSH and CART peaks in PFG animals were delayed from P20 to P30 when compared to CG. In the LH, CART was more intense in PFG animals than in UFG and CG ones by P20, and, by P30, UFG immunostaining became less intense than in CG. In conclusion, aproteic diet altered the ontogenetic distribution of both anorexigenic molecules. In the PVN, the peak was delayed to P30, which coincides with the leptin peak and follows the previously described NPY (orexigenic) peak in this model. The permanent LH CART and α-MSH increase may be associated with the previously observed PFG hypophagia.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice.

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1ß immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Malnutrition during late pregnancy exacerbates high-fat-diet-induced metabolic dysfunction associated with lower sympathetic nerve tonus in adult rat offspring.

Objectives: We aimed to assess the effects of a maternal protein-caloric restriction diet during late pregnancy on the metabolism of rat offspring fed a high-fat diet (HFD) during adulthood.Methods: During late pregnancy, rat dams received either a low-protein (4%; LP group) or normoprotein (23%; NP group) diet. After weaning, the offspring were fed a standard diet (Control; C). Male offspring (60 days old) from both groups were then fed either the C diet or HFD until they were 90 days old. The adult offspring and maternal metabolic parameters and autonomic nervous system (ANS) were then evaluated.Results: Dams exhibited low body weight gain and food intake during the LP diet consumption. At lactation, these dams showed high body weight gain, hypoinsulinemia and hyperglycemia. The maternal LP diet resulted in low body weights for the pups. There were also no differences in the metabolic parameters between the adult LP offspring that were fed the C diet and the NP group. Adults of both groups that were fed the HFD developed obesity associated with altered insulin/ glucose homeostasis and altered ANS activity; however, the magnitudes of these parameters were higher in the LP group than in the NP group.Conclusions: Maternal protein malnutrition during the last third of pregnancy malprograms the metabolism of rat offspring, resulting in increased vulnerability to HFD-induced obesity, and the correlated metabolic impairment might be associated with lower sympathetic nerve activity in adulthood.

Consumption of a high-fat diet does not potentiate the deleterious effects on lipid and protein levels and body development in rats subjected to maternal protein restriction.

Maternal undernutrition may cause injuries in several organs of the offspring, as well as lead to diseases in adulthood. Obesity and/or the consumption of a high-fat diet may also induce metabolic and cardiorespiratory diseases. We hypothesized that the consumption of a post-weaning high-fat diet would potentiate the deleterious effects of maternal protein undernutrition. This study evaluated the effects of the association of a low-protein diet during gestation and lactation with a post-weaning high-fat diet on the biochemical and ventilatory parameters of rats. Male Wistar rats from mothers who received a low-protein (9% of protein) or normoprotein diet during pregnancy and lactation received a high-fat (32% of total kilocalories from lipids) or a normal fat diet after weaning. Mass gain and somatic growth of the offspring were monitored. Also examined were biochemical chemical parameters and respiratory frequency, tidal volume (volume of air displaced in each normal respiratory cycle when extra effort is not applied), and pulmonary ventilation. Offspring from undernourished mothers presented lower birth weight (P = .0225), which remained until the end of lactation (P < .01). The rats that consumed high-fat diet and had been submitted to maternal undernutrition presented higher tidal volume when compared to the ones that consumed control diet at the 21st day of life (P Ë‚ .05). At 30 and 90 days, no further ventilatory changes were observed. Our data show that the consumption of a high-fat diet post-weaning did not seem to potentiate the changes induced by maternal undernutrition.

Short-Term Creatine Supplementation May Alleviate the Malnutrition-Inflammation Score and Lean Body Mass Loss in Hemodialysis Patients: A Pilot Randomized Placebo-Controlled Trial.

BACKGROUND: Creatine supplementation has been proposed to alleviate muscle loss in various populations, but has not been investigated in hemodialysis (HD) patients. Thus, our objective was to evaluate whether creatine supplementation could attenuate the loss of lean body mass (LBM) and malnutrition-inflammation score (MIS) in HD patients. METHODS: A randomized, placebo-controlled, double blind, parallel-design study included HD patients, of both sexes, aged 18-59 years. The patients were allocated to a Placebo Group (PG; n = 15; received maltodextrin, 1st week: 40 g/day and 2nd-4th weeks: 10 g/day) and a Creatine Group (CG; n = 15; received creatine plus maltodextrin, 1st week: 20 g/day of creatine plus 20 g/day of maltodextrin and 2nd-4th weeks: 5 g/day of creatine plus 5 g/day of maltodextrin). Pre and post the intervention, patients were evaluated for food intake, MIS, body composition and biochemical parameters. RESULTS: CG group attenuated the MIS (Pre: 5.57 ± 0.72 vs. Post: 3.85 ± 0.47 score, P = 0.003) compared with PG (Pre: 5.71 ± 0.97 vs. Post: 5.36 ± 0.95 score, P = 0.317) (supplement × time P = 0.017, effect size: 0.964). The change of LBM was greater in CG than in PG (CG: Δ0.95 vs PG: Δ0.13 kg). At post-intervention, 28.6% of PG patients presented LBM loss and 71.4% remain stable. In contrast, 14.4% of CG patients had LBM loss, 42.8% remain stable and 42.8% gained. Food intake and quality of life did not change. CG increased the BMI and gait speed in post-compared to pre-moment, but no difference among the groups. CONCLUSION: In HD patients, four weeks of creatine supplementation may alleviate the MIS as well as attenuate the LBM loss compared to placebo.

Perinatal over- and underfeeding affect hypothalamic leptin and ghrelin neuroendocrine responses in adult rats.

BACKGROUND: Changes in the nutritional supply during the perinatal period can lead to metabolic disturbances and obesity in adulthood. OBJECTIVE: The divergent litter size model was used to investigate the hypothalamic sensitivity to leptin and ghrelin as well as the mechanisms involved in the disruption of food intake and energy expenditure. METHODS: On postnatal day 3 (P3), male Wistar rats were divided into 3 groups: small litter (SL - 3 pups), normal litter (NL - 10 pups), and large litter (LL - 16 pups). Animals at P60 were intraperitoneally treated with leptin (500 µg/Kg), ghrelin (40 µg/Kg), or vehicle (0.9% NaCl) at 5 pm and the following parameters were assessed: food intake and body weight; immunostaining of p-STAT-3 in the hypothalamus; Western Blotting analysis of p-AMPKα and UCP2 in the mediobasal hypothalamus (MBH), and UCP1 in the interscapular brown adipose tissue (BAT); or heat production, VO2, VCO2, and locomotor activity. RESULTS: SL rats had earlier leptin and ghrelin surges, while LL rats had no variations. At P60, after leptin treatment, LL rats showed hypophagia and increased p-STAT-3 expression in the arcuate nucleus, but SL rats had no response. After ghrelin treatment, LL rats did not have the orexigenic response or AMPKα phosphorylation in the MBH, while SL animals, unexpectedly, decreased body weight gain, without changes in food intake, and increased metabolic parameters and UCP1 expression in the BAT. CONCLUSIONS: Changes in the nutritional supply at early stages of life modify leptin and ghrelin responsiveness in adulthood, programming metabolic and central mechanisms, which contribute to overweight and obesity in adulthood.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.