The influences of low protein diet on the intestinal microbiota of mice.

Recent research suggests that protein deficiency symptoms are influenced by the intestinal microbiota. We investigated the influence of low protein diet on composition of the intestinal microbiota through animal experiments. Specific pathogen-free (SPF) mice were fed one of four diets (3, 6, 9, or 12% protein) for 4 weeks (n = 5 per diet). Mice fed the 3% protein diet showed protein deficiency symptoms such as weight loss and low level of blood urea nitrogen concentration in their serum. The intestinal microbiota of mice in the 3% and 12% protein diet groups at day 0, 7, 14, 21 and 28 were investigated by 16S rRNA gene sequencing, which revealed differences in the microbiota. In the 3% protein diet group, a greater abundance of urease producing bacterial species was detected across the duration of the study. In the 12% diet protein group, increases of abundance of Streptococcaceae and Clostridiales families was detected. These results suggest that protein deficiency may be associated with shifts in intestinal microbiota.

Effect of low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate higher than 60 mL/min/1.73 m2 with or without albuminuria.

BACKGROUND: We aimed to investigate the effect of a low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate (eGFR) ≧60 mL/min/1.73 m2 with or without albuminuria using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We analysed participants in the NHANES from 2003 to 2010. We excluded participants with an eGFR less than 60 mL/min/1.73 m2 from the analyses. Low-protein intake was defined as a protein intake of less than 0.8 g/kg/day. The Healthy Eating Index 2010 was used to assess diet quality. The vital status of all participants in the NHANES was determined by linking to the National Death Index through the end of 2011. The hazard ratios (HRs) for the association of low-protein intake and mortality were determined using weighted Cox proportional hazards regression models. RESULTS: A total of 7730 participants were included in the analyses. After a median follow up of 4.7 years, 462 participants died. A low-protein intake was associated with a higher risk of mortality (HRs 1.394, 95% CI 1.121-1.734, P = .004) with adjustment for diet quality and relevant risk factors. The higher risk of mortality associated with a low-protein intake was consistent in subjects with or without albuminuria (P interaction .280). CONCLUSION: A protein intake of less than 0.8 g/kg/day was associated with a higher risk of mortality in subjects with an eGFR ≧60 mL/min/1.73 m2 , irrespective of whether they had albuminuria.

Impairment of G-CSF receptor on granulocytic progenitor cells causes neutropenia in protein malnutrition.

OBJECTIVE: It is well known that protein malnutrition (PM) states can affect hematopoiesis, leading to severe leukopenia and reduced number of granulocytes, which act as the first line of defense, and are important to the innate immune response. The aim of this study was to elucidate some of the mechanisms involved in the impairment of granulopoiesis in PM. METHODS: Male C57BL/6 mice were submitted to PM with a low-protein diet containing 2% protein. Control mice were fed a 12% protein-containing diet. Bone marrow histology and the percentage of granulocytic progenitors were evaluated after in vivo granulocyte-colony stimulating factor (G-CSF) stimulus. Cell proliferation, STAT3 signaling, and the expression of G-CSF receptor were evaluated in hematopoietic progenitor cells. RESULTS: Malnourished animals presented with leukopenia associated with reduced number of granulocytes and reduced percentage of granulocytic progenitors; however, no differences were observed in the regulatory granulopoietic cytokine G-CSF. Additionally, the malnourished group presented with impaired response to in vivo G-CSF stimulus compared with control animals. PM was implicated in decreased ability of c-Kit+ cells to differentiate into myeloid progenitor cells and downregulated STAT3 signaling. Furthermore, the malnourished group exhibited reduced expression of G-CSF receptor on granule-monocytic progenitors. This reduced expression was not completely reversible with G-CSF treatment. CONCLUSIONS: This study implies that PM promotes intrinsic alterations to hematopoietic precursors, which result in hematologic changes, mainly neutropenia, observed in peripheral blood in PM states.

Feeding modality is a barrier to adequate protein provision in children receiving continuous renal replacement therapy (CRRT).

BACKGROUND: Critically ill children have a high prevalence of malnutrition. Children with acute kidney injury experience high rates of protein debt. Previous research has indicated that protein provision is positively associated with survival. METHODS: This was a prospective observational study of all patients receiving CRRT for greater than 48 h at our tertiary care institution. Patients with inborn errors of metabolism were excluded. Data collection included energy, protein, and fluid volume intakes, anthropometrics, feeding modality, and route of nutrition intake. RESULTS: Forty-one patients 9 ± 6.8 years of age, 66% male, received CRRT over a 10-month time period. CRRT treatment was 17.3 ± 25 days. Forty-one percent were malnourished via anthropometric criteria at CRRT start. Median protein delivery was 2 g/kg/day (IQR 1.4-2.5). Fifty-one percent received a combination of parenteral nutrition (PN) and enteral/oral feedings (EN), 34% received only PN, and 12% received only EN. Percentage of time meeting protein goals by modality was 27.6%, 34.6%, and 65.3% for those patients receiving solely EN, PN, and EN + PN combination, respectively. When weaned to only EN support from combination PN + EN, the average percentage of time protein goals were met decreased to 20.5% (p < 0.01). CONCLUSIONS: Without PN, patients on enteral/oral nutrition support fail to meet appropriate protein prescription. Transition of parenteral to enteral feeds was identified as a period of nutritional risk in children receiving CRRT.

Acrodermatitis enteropática y desnutrición proteica posterior a cirugía bariátrica / Enteropathic acrodermatitis and proteic nuttrution after bariatric surgery

La utilización de la cirugía bariátrica ha ido en aumento por su efectividad a largo plazo en el mantenimiento del peso perdido, en la reducción drástica de comorbilidades y mortalidad global. El bypass biliopancreático es una de las técnicas bariátricas más eficaces para la pérdida y mantenimiento del peso con menor restricción dietética. Se presenta un caso clínico de una mujer intervenida previamente de by-pass biliopancreático y que presento signos de malnutrición por deficiencia del zinc. Se describe la evolución de la enferma y se discuten las características y repercusiones que la deficiencia produce en la paciente

The use of bariatric surgery has been increasing due to its long-term effectiveness in maintaining lost weight, in drastically reducing comorbidities and overall mortality. Biliopancreatic bypass is one of the most effective bariatric techniques for weight loss and maintenance with less dietary restriction. We present a clinical case of a woman who had previously undergone biliopancreatic bypass and had signs of zinc malnutrition. The evolution of the patient is described and the characteristics and repercussions that the deficiency produces in the patient are discussed

Development and validation of a short food questionnaire to screen for low protein intake in community-dwelling older adults: The Protein Screener 55+ (Pro55+).

In old age, sufficient protein intake is important to preserve muscle mass and function. Around 50% of older adults (65+ y) consumes ≤1.0 g/kg adjusted body weight (BW)/day (d). There is no rapid method available to screen for low protein intake in old age. Therefore, we aimed to develop and validate a short food questionnaire to screen for low protein intake in community-dwelling older adults. We used data of 1348 older men and women (56-101 y) of the LASA study (the Netherlands) to develop the questionnaire and data of 563 older men and women (55-71 y) of the HELIUS study (the Netherlands) for external validation. In both samples, protein intake was measured by the 238-item semi-quantitative HELIUS food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to predict protein intake ≤1.0 g/kg adjusted BW/d (based on the HELIUS FFQ). Candidate predictor variables were FFQ questions on frequency and amount of intake of specific foods. In both samples, 30% had a protein intake ≤1.0 g/kg adjusted BW/d. Our final model included adjusted body weight and 10 questions on the consumption (amount on average day or frequency in 4 weeks) of: slices of bread (number); glasses of milk (number); meat with warm meal (portion size); cheese (amount and frequency); dairy products (like yoghurt) (frequency); egg(s) (frequency); pasta/noodles (frequency); fish (frequency); and nuts/peanuts (frequency). The area under the receiver operating characteristic curve (AUC) was 0.889 (95% CI 0.870-0.907). The calibration slope was 1.03 (optimal slope 1.00). At a cut-off of ≤0.8 g/kg adjusted BW/d, the AUC was 0.916 (96% CI 0.897-0.936). Applying the regression equation to the HELIUS sample, the AUC was 0.856 (95% CI 0.824-0.888) and the calibration slope 0.92. Regression coefficients were therefore subsequently shrunken by a linear factor 0.92. To conclude, the short food questionnaire (Pro55+) can be used to validly screen for protein intake ≤1.0 g/kg adjusted BW/d in community-dwelling older adults. An online version can be found at www.proteinscreener.nl. External validation in other countries is recommended.

[Protein deficiency - a rare nutrient deficiency]. / Svårt att få brist på protein ­ för högt intag större risk - Lagom mängd mat ­ oavsett kosttyp ­ ger tillräckligt mycket.

There is a widespread myth that we have to be careful about what we eat so that we do not cause protein deficiency. We know today that it is virtually impossible to design a calorie-sufficient diet, whether it is based on meat, fish, eggs, various vegetarian diets or even unprocessed whole natural plant foods, which is lacking in protein and any of the amino acids. The body is capable of taking incomplete proteins and making them complete by utilizing the amino acid recycling mechanism. The majority of amino acids absorbed from the intestinal tract are derived from recycled body protein. Research shows that high levels of animal protein intake may significantly increase the risk of premature mortality from all causes, among them cardiovascular diseases, cancer and type 2 diabetes.

Paricalcitol and Peritoneal Protein Loss in Peritoneal Dialysis: A Double-Center Study.

BACKGROUND/AIMS: Peritoneal protein loss (PPL) is associated with cardiovascular disease and mortality in peritoneal dialysis (PD). Controversial results have been published about the effect of paricalcitol in PPL among PD patients. This study intends to analyze the relationship between paricalcitol and PPL in PD. METHODS: In a retrospective study, prevalent PD patients were divided into 2 groups: "with paricalcitol" and "without paricalcitol". X2-test, Student's t test, Pearson correlation coefficient and Logistic Regression analysis were applied. RESULTS: Eighty-two patients were included. PPL was lower among patients medicated with paricalcitol (5.17 ± 1.71 vs. 6.79 ± 2.10 g/24 h, p = 0.0001). In multivariate analysis, paricalcitol and dialysate/plasma ratio of creatinine (D/P creatinine) were independently related to PPL (OR 4.270 [1.437-12.684], p = 0.009 and OR 0.205 [0.064-0.659], p = 0.008, respectively), adjusted for diabetes. CONCLUSION: Paricalcitol and D/P creatinine were independently related to PPL. Paricalcitol may have an effect on PPL in PD patients.

Parenteral nutrition in intensive care patients: medicoeconomic aspects.

PURPOSE OF REVIEW: Parenteral nutrition (PN) alone or as supplemental parenteral nutrition (SPN) has been shown to prevent negative cumulative energy balance, to improve protein delivery and, in some studies, to reduce infectious morbidity in ICU patients who fail to cover their needs with enteral nutrition (EN) alone. RECENT FINDINGS: The optimization of energy provision to an individualized energy target using either early PN or SPN within 3-4 days after admission has recently been reported to be a cost-saving strategy mediated by a reduction of infectious complications in selected intensive care patients. SUMMARY: EN alone is often insufficient, or occasionally contraindicated, in critically ill patients and results in growing energy and protein deficit. The cost benefit of using early PN in patients with short-term relative contraindications to EN has been reported. In selected patients SPN has been associated with a decreased risk of infection, a reduced duration of mechanical ventilation, a shorter stay in the ICU. Altogether four studies have investigated the costs associated with these interventions since 2012: two of them from Australia and Switzerland have shown that optimization of energy provision using SPN results in cost reduction, conflicting with other studies. The latter encouraging findings require further validation.

The relevance of dietary protein after bariatric surgery: what do we know?

PURPOSE OF REVIEW: The growing obesity epidemic is associated with an increased demand for bariatric surgery with Roux-en-Y Gastric Bypass and Sleeve Gastrectomy as the most widely performed procedures. Despite beneficial consequences, nutritional complications may arise because of anatomical and physiological changes of the gastrointestinal tract. The purpose of this review is to provide an update of the recent additions to our understanding of the impact of bariatric surgery on the intake, digestion and absorption of dietary protein. RECENT FINDINGS: After bariatric surgery, protein intake is compromised because of reduced gastric capacity and aversion for certain foods. A minority of patients reaches the recommended protein intake of minimal 60 g per day, which results in the loss of fat-free mass rather than the desired loss of fat mass. Despite inadequate protein intake, protein digestion and absorption do not seem to be impaired suggesting that other mechanisms could counteract the reduced secretion of digestive enzymes and their delayed inlet. SUMMARY: After bariatric surgery, protein supplementation or diet enrichment could attribute to achieve the minimal recommended protein intake and benefit the amount and composition of postoperative weight loss.

Protein malnutrition after weaning disrupts peripheral clock and daily insulin secretion in mice.

Changes in nutritional state may alter circadian rhythms through alterations in expression of clock genes. Protein deficiency has a profound effect on body metabolism, but the effect of this nutrient restriction after weaning on biological clock has not been explored. Thus, this study aims to investigate whether the protein restriction affects the daily oscillation in the behavior and metabolic rhythms, as well as expression of clock genes in peripheral tissues. Male C57BL/6 J mice, after weaning, were fed a normal-protein (NP) diet or a low-protein (LP) diet for 8 weeks. Mice fed an LP diet did not show difference in locomotor activity and energy expenditure, but the food intake was increased, with parallel increased expression of the orexigenic neuropeptide Npy and disruption of the anorexigenic Pomc oscillatory pattern in the hypothalamus. LP mice showed disruption in the daily rhythmic patterns of plasma glucose, triglycerides and insulin. Also, the rhythmic expression of clock genes in peripheral tissues and pancreatic islets was altered in LP mice. In pancreatic islets, the disruption of clock genes was followed by impairment of daily glucose-stimulated insulin secretion and the expression of genes involved in exocytosis. Pharmacological activation of REV-ERBα could not restore the insulin secretion in LP mice. The present study demonstrates that protein restriction, leading to development of malnutrition, alters the peripheral clock and metabolic outputs, suggesting that this nutrient provides important entraining cues to regulate the daily fluctuation of biological clock.

Associations between neighborhood food environments and deficient protein intake among elderly people in a metropolitan suburb: A case study in Kisarazu city, Japan.

OBJECTIVES: Living in a poor food environment and its association with an increased risk of inadequate nutrient intake are increasingly important issues in Japan due to an increase in the elderly population. METHODS: The present study examined the relationships between neighborhood food environment and the protein and fat intakes of elderly Japanese individuals (n = 181) living in the metropolitan Tokyo suburb of Kisarazu. RESULTS: A logistic regression analysis adjusted for sociodemographic and shopping behavior variables revealed associations between subjectively evaluated poor neighborhood food environment and deficient protein intake. However, there was no significant association between excessive fat intake and neighborhood food environments. CONCLUSION: The findings demonstrate that living in a poor neighborhood food environment, which is becoming increasingly prevalent in Japan and other developed countries, has the potential to result in malnutrition, or at least in a low-quality diet, in elderly populations.

[Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency].

Activity of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and the NAD(+)/NADН ratio were studied in the liver mitochondrial fraction of rats with toxic hepatitis induced by acetaminophen under conditions of alimentary protein deprivation. Acetaminophen-induced hepatitis was characterized by a decrease of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase activities, while the mitochondrial NAD(+)/NADН ratio remained at the control level. Modeling of acetaminophen-induced hepatitis in rats with alimentary protein caused a more pronounced decrease in the activity of NAD(+)-dependent dehydrogenases studied and a 2.2-fold increase of the mitochondrial NAD(+)/NADН ratio. This suggests that alimentary protein deprivation potentiated drug-induced liver damage.

Clinical outcomes of duodenal switch with a 200-cm common channel: a matched, controlled trial.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) with a 100-cm common channel has been our treatment of choice for morbid obesity since the early 1990s. This procedure offers excellent long-term weight loss but can be associated with significant side effects. OBJECTIVES: To assess the effect on clinical and nutritional parameters of increasing the common channel to 200 cm. SETTINGS: University-affiliated tertiary care center. METHODS: Patients who underwent a BPD-DS with a 200-cm common channel (study group, n = 36) were matched 1:1 for age, sex, body mass index (BMI), and main co-morbidities with patients who underwent a BPD-DS with a 100-cm common channel (control group). The strict alimentary limb was 150 cm in both groups. RESULTS: The mean age was 55±9 versus 53±7 years (P = .3), with 50% women and a BMI of 49±8 kg/m(2) versus 50±6 kg/m(2) (P = .9). Follow-up rate was 97%, with a minimum follow-up of 3 years. There were no significant differences in the remission rate of major co-morbidities between the 2 groups. At 3 years, the excess weight loss was 61±22% versus 68±18% (P = .18) and the total weight loss was 33±11% versus 38±9% (P = .055) in the study group versus control group, respectively. The study group had a lower incidence of severe protein deficiency (11% versus 19%, P = .3) and hyperparathyroidism (17.1% versus 35.3%, P = .17); required a lower amount of vitamins A and D (P<.05); and had a decreased number of daily bowel movements (2.0 versus 2.9, P = .03). CONCLUSION: In this population, BPD-DS with a 200-cm common channel offered similar remission rate of co-morbidities compared with standard BPD-DS. It was associated with similar weight loss at nadir, followed by a more significant weight regain. It might yield a lower rate of nutritional complications. Long-term randomized data are needed to detect other potential advantages.

Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding.

BACKGROUND: The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity. METHOD: In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. RESULTS: Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. CONCLUSIONS: Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term.

Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency.

The rate of superoxide anion radical, hydroxyl radical and hydrogen peroxide generation, the level of oxidative modification of mitochondrial proteins in the liver of rats with toxic hepatitis was investigated on the background of alimentary protein deficiency. We did not find significant increases of the intensity of free radical processes in liver mitochondria of rats maintained on the protein-deficient ration. The most significant intensification of free radical processes in liver mitochondria is observed under the conditions of toxic hepatitis, induced on the background of alimentary protein deprivation. Under these conditions the aggravation of all studied forms of reactive oxygen species generation was observed in liver mitochondria. The generation rates were increased as follows: O2 ­ by 1.7 times, Н2О2 ­ by 1.5 times, •ОН ­ practically double on the background of accumulation of oxidized mitochondria-derived proteins. The established changes in thiol groups' redox status of respiratory chain proteins insoluble in 0.05 M sodium-phosphate buffer (pH 11.5), and changes of their carbonyl derivatives content may be considered as one of the regulatory factors of mitochondrial energy-generating function.

Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up.

BACKGROUND: Roux-en-Y gastric bypass (GBP) and sleeve gastrectomy (SG) have increased dramatically, potentially increasing the prevalence of nutritional deficiencies. The aim of this study was to analyze the effects of food restriction during the first year after bariatric surgery (BS) on nutritional parameters. METHODS: Twenty-two and 30 obese patients undergoing GBP and SG were prospectively followed at baseline and 3, 6, and 12 months after BS (N = 14 and N = 19 at T12). We evaluated food intake and nutrient adequacy (T0, T3, T12), as well as serum vitamin and mineral concentration (T0, T3, T6, T12). RESULTS: At baseline, GBP and SG patients had similar clinical characteristics, food intake, nutrient adequacy, and serum concentration. The drastic energy and food reduction led to very low probabilities of adequacy for nutrients similar in both models (T3, T12). Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 37 and 38% of GBP patients and 57 and 52% of SG patients, respectively, at T3 and T12. Conversely, despite the low probabilities of adequacy observed at T3 and T12, systematic multivitamin and mineral supplementation after GBP and SG prevented most nutritional deficiencies. CONCLUSIONS: GBP and SG have comparable effects in terms of energy and food restriction and subsequent risk of micronutrient and protein deficiencies in the first year post BS. Such results advocate for a cautious monitoring of protein intake after GPB and SG and a systematic multivitamin and mineral supplementation in the first year after SG.

Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring.

BACKGROUND AND OBJECTIVES: Studies in humans and animal models have established a close relationship between early environment insult and subsequent risk of development of non-communicable diseases, including the cardiovascular. Whereas experimental evidences highlight the early undernutrition and the late cardiovascular disease relation, the central mechanisms linking the two remain unknown. Owing to the oxidative balance influence in several pathologies, the aim of the present study was to evaluate the effects of maternal undernutrition (i.e. a low-protein (LP) diet) on oxidative balance in the brainstem. METHODS AND RESULTS: Male rats from mothers fed with an LP diet (8% casein) throughout the perinatal period (i.e. gestation and lactation) showed 10× higher lipid peroxidation levels than animals treated with normoprotein (17% casein) at 100 days of age. In addition, we observed the following reductions in enzymatic activities: superoxide dismutase, 16%; catalase, 30%; glutathione peroxidase, 34%; glutathione-S-transferase, 51%; glutathione reductase, 23%; glucose-6-phosphate dehydrogenase, 31%; and in non-enzymatic glutathione system, 46%. DISCUSSION: This study is the first to focus on the role of maternal LP nutrition in oxidative balance in a central nervous system structure responsible for cardiovascular control in adult rats. Our data observed changes in oxidative balance in the offspring, therefore, bring a new concept related to early undernutrition and can help in the development of a new clinical strategy to combat the effects of nutritional insult. Wherein the central oxidative imbalance is a feasible mechanism underlying the hypertension risk in adulthood triggered by maternal LP diet.

Exposure to increased levels of estradiol during development can have long-term effects on the response to undernutrition in female rats.

OBJECTIVES: Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here, we analyze whether the early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. METHODS: Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time polymerase chain reaction was performed to determine expression in the hypothalamus of agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript. Plasma estradiol, testosterone, and adiponectin levels were measured by enzyme-linked immunosorbent assay. Total and acylated ghrelin levels were measured in plasma by radioimmunoassay. Insulin and leptin were measured by mulitplex immunoassays. RESULTS: Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels, and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol, and acylated ghrelin levels. DISCUSSION: Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism.