leptin and Protein-Energy-Malnutrition

Anorexia nervosa is a frequent disorder especially among adolescent girls and young women, with high morbidity, mortality, and relapse rates. To date, no single therapeutic approach has proved to be superior to others (Herpertz et al., 2011). It remains unclear how its etiology and pathology are encoded within cognitive, neural, and endocrinological processes that modulate important mechanisms in appetitive processing and weight regulation. Yet, several trait characteristics have been identified in AN which might reflect predisposing factors. Further, altered levels of neuropeptides and hormones that regulate appetite and feeding behavior have been found during both the acute and the recovered state, pointing to dysfunctional mechanisms in AN that persist even after malnutrition has ceased. Researchers are also hoping that brain imaging techniques will allow for a more detailed investigation of the neural basis of reward and punishment sensitivity that appears to be altered in AN. The integration and extension of recent findings in these areas will hopefully provide a more comprehensive understanding of the disorder and hence enable the development of more effective treatments.. Anorexia nervosa ist eine psychosomatische Erkrankung mit hoher Morbidität und Mortalität, die meist bei Mädchen und jungen Frauen auftritt. Bisher gibt es keine Hinweise auf die Überlegenheit eines bestimmten Therapieverfahrens (Herpertz et al., 2011). Während der klinische Phänotyp bislang im Fokus stand, werden immer häufiger Methoden und Ansätze verwendet, die in der Anorexieforschung bisher unterrepräsentiert waren. Diese beinhalten zum einen die Untersuchung endokrinologischer Merkmale wie z. B. Hormone und andere Mediatoren, die wichtige Vorgänge der Gewichts- und Appetitregulation beeinflussen, aber auch die Erforschung von kognitiven Veränderungen und Persönlichkeitsmerkmalen, die oft auch nach Ende der akuten Krankheitsphase noch messbar sind. Dabei ist es vor allem wichtig, prädisponierende und die Krankheit aufrechterhaltende Faktoren zu identifizieren und zu unterscheiden. Nicht zuletzt ermöglichen bildgebende Verfahren seit einigen Jahren die genauere Untersuchung von funktionellen Zusammenhängen verschiedener Gehirnareale, die diesen prädisponierenden und aufrechterhaltenden Faktoren zugrunde liegen könnten. Letztendlich ist es das Ziel, mit Hilfe dieser neurowissenschaftlichen Methoden langfristig neuropsychologische und biologische Merkmale zu ermitteln, die ein besseres Verständnis der zugrundeliegenden Mechanismen von Anorexia nervosa ermöglichen und damit zur Verbesserung der Behandlung beitragen.

Topics: Adolescent; Anorexia Nervosa; Appetitive Behavior; Brain; Cognition Disorders; Female; Humans; Hypothalamus; Leptin; Magnetic Resonance Imaging; Neuropsychological Tests; Neurotransmitter Agents; Protein-Energy Malnutrition; Sense of Coherence; Weight Gain; Young Adult

Chronic uremia is often characterized by wasting of muscle and fat mass, which has been defined as protein-energy wasting (PEW), and is responsible for substantial worsening of patient outcome in terms of morbidity and mortality, mostly from cardiovascular events. Despite major advances in patient treatment, nutritional outcome in patients with end-stage renal disease has not improved substantially in recent years. Extensive research in this field has provided plausible explanations for this limitation by indicating that the pathogenesis of PEW in kidney disease is complex and multifactorial. Complexity involves underlying metabolic alterations, including inflammation, oxidative stress, and insulin resistance. In addition, patient heterogeneity is increasing with large numbers of obese individuals as a result of the ongoing obesity epidemics. Several tissues are involved in cross-talk and contribute to metabolic derangements, including adipose tissue, the gut, and the central nervous system, with novel mediators including the gastric hormone ghrelin. Acknowledging its complex pathogenesis may favor the development of novel and more effective therapeutic tools for PEW. These should ideally be effective in treating the underlying common mechanisms of wasting, which appear to include oxidative stress, inflammation, and insulin resistance.

Topics: Animals; Ghrelin; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Obesity; Oxidative Stress; Protein-Energy Malnutrition

Topics: Animals; Comorbidity; Diabetes Mellitus; Global Health; HIV Infections; Humans; Infections; Leptin; Malaria; Malnutrition; Measles; Obesity; Protein-Energy Malnutrition; Risk Factors; T-Lymphocytes; Tuberculosis

Appetite and food intake decrease with normal ageing, predisposing to the development of under-nutrition. Under-nutrition is common in older people and has been implicated in the development and progression of chronic diseases commonly affecting the elderly, as well as in increasing mortality. An understanding of the factors that contribute to the physiological and pathological declines in food intake in older people is likely to aid in the development of effective forms of prevention and treatment. Ageing affects many of the endocrine factors involved in the control of appetite and feeding but few studies have been performed in humans to clarify these changes. Possible hormonal causes of the anorexia of ageing include increased activity of cholecystokinin, leptin and various cytokines and reduced activity of ghrelin and testosterone.

Topics: Aged; Aging; Androgens; Animals; Anorexia; Appetite Regulation; Cholecystokinin; Cytokines; Ghrelin; Hormones; Humans; Leptin; Neurotransmitter Agents; Peptide Hormones; Protein-Energy Malnutrition

Protein-energy malnutrition is a major comorbid condition in persons with renal disease. A variety of interventions have been implemented to supplement protein and energy intake in malnourished patients with renal disease, but the prevalence of protein-energy malnutrition remains high. Leptin, a hormone secreted by adipose tissue, decreases food intake via neuroendocrine systems in the hypothalamus in persons with normal renal function. Serum leptin levels are elevated in patients with chronic renal insufficiency and end-stage renal disease, and experimental evidence suggests a possible role for leptin in the development of protein-energy malnutrition in this population. Release of leptin from adipocytes may be stimulated by cytokines mediating the inflammatory response, which is frequently pronounced in patients with end-stage renal disease receiving hemodialysis and peritoneal dialysis. This article provides an overview of research conducted on serum leptin levels in different stages of renal disease, and the relationship among serum leptin, body composition, biochemical indexes, and markers of inflammation in persons with end-stage renal disease. Effects of intradialytic parenteral nutrition and anabolic factors on leptin levels and nutritional status are briefly reviewed.

Topics: Cytokines; Energy Intake; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Nutritional Status; Peritoneal Dialysis; Prevalence; Protein-Energy Malnutrition; Renal Dialysis

A large proportion of chronic diseases affecting older persons can be either prevented or significantly improved by improving nutrition. This places an increased burden on health care professionals caring for older persons. Screening for malnutrition at an early stage allows the intervention to be most successful. History, physical examination, and anthropometric measurements are essential parts of any nutritional evaluation. However, these tools can be highly subjective and rely heavily on the knowledge and experience of the evaluator. Incorporating biochemical measurements in the routine nutritional assessment provides an often-needed objective dimension. Interpreting these measurements must take into consideration the normal biological changes seen with aging. In this article, we review many of the biochemical parameters used in nutritional assessment and their relation to morbidity and mortality, with a special focus on normal changes seen with aging.

Topics: Aged; Aging; Blood Proteins; Cholesterol; Clinical Chemistry Tests; Creatinine; Humans; Immunity; Leptin; Nutrition Assessment; Protein-Energy Malnutrition

Protein-energy malnutrition is still a problem in patients with chronic renal failure, especially during replacement renal therapy. The chronic inflammatory status in these patients intensifies the malnutrition, as well as making treatment more complicated. The aim of the present study was to estimate the influence of oral supplementation on the nutritional status of malnourished hemodialysis (HD) patients depending on the existence of an inflammatory state.. To study the influence of oral supplementation on nutrition status, 30 HD patients with protein-energy malnutrition characteristics and 25 well-nourished HD patients were enrolled in the study. Malnourished HD patients were prescribed Renilon 7.5 at an oral intake dose of 125 mL twice a day for 3 months. The nutritional status was characterized based on body mass index, Subjective Global Assessment score, serum albumin and prealbumin concentrations. The intensity of the inflammatory state was determined by C-reactive protein and interleukin-6. Serum concentrations of leptin and adiponectin were also measured.. After 3 months of supplementation, malnourished patients had an increase in prealbumin, albumin, and leptin concentrations. No statistically significant differences were observed between patients lacking inflammation and those with inflammation.. The results indicate an improvement in the nutritional status of HD patients who were prescribed an oral supplementation. Furthermore, patients with inflammatory state characteristics also benefited from Renilon 7.5 treatment.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Dietary Supplements; Female; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin

Dialysis patients with a high body mass index are less likely to experience severe anemia. Leptin, a hormone secreted by adipocytes, may have a role in protecting against renal anemia. The aim of the present study is to determine the effect of an increase in serum leptin levels by increasing energy intake on recombinant human erythropoietin (rHuEPO) response in long-term hemodialysis (HD) patients.. We enrolled 65 long-term HD patients to explore the association between leptin level and rHuEPO response by classifying them as either high- or low-leptin individuals (phase 1). Thereafter, 39 patients with malnutrition by means of Subjective Global Assessment were randomly assigned to high-energy and high-protein (an extra 475 kcal and 16.6 g of protein daily; group A; n = 12) or standard-energy, but high-protein (an extra 67.2 kcal and 16.8 g of protein daily; group B; n = 27), supplementation for 12 weeks. Serial serum leptin levels, nutritional measures, and hematologic parameters were obtained. Age- and sex-matched well-nourished patients (group C; n = 16) not administered extra nutritional supplementation served as control subjects (phase 2).. In phase 1, a significantly lower erythropoietin dose, greater hematocrit, and better nutritional measures were observed in the high-leptin group (P < 0.001). In phase 2, there was a significant increase in body fat mass (P = 0.001) and median serum leptin levels (P < 0.001) in response to 12 weeks of high-energy supplementation in group A, accompanied by markedly improved erythropoiesis (P < 0.05) compared with groups B and C.. Hyperleptinemia reflects better nutritional status and rHuEPO response in long-term HD patients. Increasing energy intake improves erythropoiesis, which may be mediated in part by an increase in serum leptin levels.

Topics: Adipose Tissue; Aged; Anemia; Body Composition; Cross-Sectional Studies; Dietary Proteins; Dietary Supplements; Drug Resistance; Energy Intake; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prospective Studies; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Malnutrition-inflammation complex syndrome and anorexia, common conditions in maintenance dialysis patients, are strongly associated with higher mortality and hospitalization and lower quality of life (QoL) in this population. Megestrol acetate, 800 mg/day, has been shown to increase appetite and food intake and to mitigate inflammation in cachectic AIDS and cancer patients, leading to weight gain, but it is also associated with side effects at this dose.. We evaluated the efficacy of the oral solution of megestrol acetate in half of its conventional dose in improving the nutritional state and inflammation in 10 hypoalbuminemic dialysis patients (albumin < 3.7 g/dL). Six women and 4 men, ages 60.2 years, took 400 mg of megestrol acetate solution daily for 16 weeks. Anthropometry, dual energy x-ray absorptiometry, 24-hour diet recalls, and biochemical measurements of nutrition and inflammation, including serum C-reactive protein and leptin, were performed.. At the end of the 16 weeks of intervention, weight and body mass index increased by 9%, body fat proportion by 31%, and triceps skinfold by 40% (P < .01). Serum albumin increased from 3.0 to 3.3 g/dL and continued to increase significantly to 3.6 g/dL after 3 months postintervention (P = .03). Serum leptin increased from 5.2 to 10.7 ng/mL (P = .09). Daily protein and energy intake increased progressively up to 27% to 42% by the end of the trial (P < or = .01). In 8 patients without acute infection, serum C-reactive protein declined from 1.24 to 0.78 mg/L (P = .06). QoL and appetite were reported to be improved. No major side effects were observed, and all 10 patients completed the 16 weeks of daily intake of megestrol acetate without interruption.. Megestrol acetate oral solution in half of its conventional dose is safe and improves the nutritional state, inflammation, and anorexia in maintenance dialysis patients. Larger-scale placebo-controlled randomized studies are needed to confirm the beneficial effects of 400 mg/day of megestrol acetate in dialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Anthropometry; Body Composition; Body Mass Index; Body Weight; C-Reactive Protein; Dietary Proteins; Energy Intake; Female; Humans; Hypoalbuminemia; Inflammation; Kidney Failure, Chronic; Leptin; Male; Megestrol Acetate; Middle Aged; Nutritional Status; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Syndrome; Treatment Outcome

The aim of the present study was to clarify the relationship between changing nutritional anthropometric data and serum leptin concentrations during the catch-up growth process in children.. Thirty children with mild protein-energy malnutrition (PEM) were followed for 6 months and their anthropometric measurements and serum leptin concentrations were recorded during follow up.. Twenty-two (73.3%) of the 30 children showed catch-up growth. All parameters and serum leptin concentrations increased during the period of catch-up growth. In the remaining eight children, weight for height, percentage standard body mass index, percentage standard body height and mean serum leptin concentrations did not show any significant increase at the 6 month follow-up. Mean serum leptin concentration was higher in children with catch-up growth than in the controls.. During recovery from malnutrition, leptin concentrations increase in relation to fat mass if the fat mass reaches a critical point, and leptin might trigger catch-up growth with its regulator effects on growth. Although weight gain was noted in both groups, an increase in leptin concentration was observed only in children who showed catch-up growth. More interestingly, the mean leptin concentration was much higher in children with PEM who had catch-up growth compared to the control group and in children who failed to have catch-up growth. In children with catch-up growth, the higher serum leptin concentrations compared to healthy children and to children without catch-up growth despite significant weight gain suggests that leptin affects nutritional status in catch-up growth as a dynamic process, rather than merely being an index of body fat content.

Topics: Body Height; Body Weight; Child; Child, Preschool; Female; Follow-Up Studies; Growth; Humans; Infant; Leptin; Male; Outpatients; Protein-Energy Malnutrition; Skinfold Thickness

The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 +/- 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P: < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P: < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P: < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P: < 0.02). Similarly, variations in leptin levels were directly related to insulin (P: < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P: < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.

Topics: Cross-Over Studies; Energy Metabolism; Female; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins; Leptin; Male; Middle Aged; Parenteral Nutrition; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Rest

In much of the developing world, severe malnutrition is the most prevalent cause of immunodeficiency and affects up to 50% of the population in some impoverished communities. As yet, we do not know how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will behave in populations with immunodeficiency caused by malnourishment. Interestingly, researchers are now speculating that, in some instances, a defective cellular immune system could paradoxically be a protective factor against severe disease in certain patients contracting SARS-CoV and SARS-CoV-2. This could be linked to the absence of T-cell activation. Based on available information presented here, it is plausible that the hyperimmune response, and subsequent cytokine storm often associated with severe coronavirus disease 2019 (COVID-19), could be "counteracted" by the defective immune response seen in individuals with malnutrition-induced leptin deficiency. In this paper, we proposed a theory that although those with malnutrition-linked leptin deficiency are at risk of SARS-CoV-2 infection, they are at lower risk of developing severe COVID-19.

Topics: Antibody Formation; Body Mass Index; COVID-19; COVID-19 Vaccines; Cytokine Release Syndrome; Developing Countries; Disease Susceptibility; Humans; Immunity, Cellular; Immunogenicity, Vaccine; Immunologic Deficiency Syndromes; Leptin; Lymphocyte Activation; Malnutrition; Models, Biological; Obesity; Protein-Energy Malnutrition; Risk; SARS-CoV-2; Severity of Illness Index; T-Lymphocytes

This study was carried out to evaluate the relationship between dietary and serum zinc and leptin levels with protein-energy wasting (PEW) in haemodialysis patients.. The study was conducted on 80 volunteer patients aged 19-65 years who received haemodialysis treatment three times a week for at least 1 year. Anthropometric measurements and body composition analyses were performed. Blood samples were collected for serum zinc and leptin and other biochemical parameters. Food consumption of the patients was recorded for 3 days. Malnutrition-inflammation score (MIS) was calculated for all patients. PEW was assessed according to the criteria recommended by the International Society of Renal Nutrition and Metabolism (ISRNM).. According to the ISRNM criteria, 38.1% of male patients and 36.8% of female patients were diagnosed with PEW. The median serum leptin levels of patients with PEW [9.0 (16.9) ng/mL] were significantly lower than those without PEW [20.7 (38.5) ng/mL] (p < 0.05). Dietary zinc intake in patients with PEW was significantly lower than that in patients without PEW (p < 0.05). However, there was no significant difference in serum zinc levels between the patients with and without PEW. In the multivariate analyses, dietary and serum zinc and leptin was associated with PEW. After controlling for several confounding factors these associations disappeared. Dietary zinc intake and serum leptin levels were inversely correlated with MİS. There was no relationship between serum leptin and dietary and serum zinc in these patients.. Dietary zinc intake and serum zinc and leptin concentration were not associated with PEW. Low serum leptin levels might be the outcome rather than the cause of PEW in haemodialysis patients.

Topics: Adult; Aged; Cross-Sectional Studies; Diet; Female; Humans; Leptin; Male; Middle Aged; Protein-Energy Malnutrition; Renal Dialysis; Young Adult; Zinc

This study aimed to evaluate plasma concentrations of leptin and total ghrelin in children with chronic kidney disease (CKD) and assess their roles in protein-energy wasting (PEW).. This study consisted of three different CKD populations [CKD group (20 patients with non-dialysis CKD), dialysis group (39 patients on dialysis), and kidney transplant (KTx) group (35 KTx recipients)] and control group (18 healthy children). Plasma leptin and total ghrelin levels were measured. Multi-frequency bioimpedance analysis was used for the assessment of fat and lean mass. PEW was defined using criteria including body mass, muscle mass, growth, serum albumin level, and protein intake.. While plasma leptin levels did not differ among the study groups, total ghrelin levels were significantly higher in the dialysis group (P < 0.001). Seven dialysis patients (18%) and one CKD patient (5%) but none of the KTx recipients met the criteria of PEW. Dialysis patients with PEW had lower plasma leptin levels compared to their counterparts (P = 0.018); however, total ghrelin levels did not differ between the two groups (P = 0.10). Low leptin level in dialysis patients was independently associated with lower fat mass index (P < 0.001) and lower height-specific SD scores of BMI (P = 0.019).. PEW is prevalent in dialysis patients. Low levels of leptin seem to be associated with PEW. Our result suggests that low leptin levels may be a consequence rather than a cause of PEW. Longitudinal studies are required to investigate this complex relationship between leptin and PEW in pediatric dialysis patients.

Topics: Adolescent; Body Fat Distribution; Body Mass Index; Child; Female; Ghrelin; Humans; Kidney Transplantation; Leptin; Male; Prevalence; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic

The aim of the study was to examine the prevalence of protein-energy wasting (PEW) in hemodialysis (HD) and peritoneal dialysis (PD) patients in our center and determine whether adiponectin and leptin are involved in the development of PEW.. Prospective (18 months).. University Hospital of Heraklion, Crete, Greece.. Seventy-four end-stage-renal-disease patients, 47 on HD and 27 on PD.. At three sequential time points (baseline, 6 and 18 months) anthropometric, nutritional and inflammatory status data were collected. Serum adiponectin and leptin were also assessed at each time point. Patients were allocated to 3 strata according to PEW severity (0, 1-2 and ≥3 criteria for PEW).. Adiponectin and leptin levels were greater among PD compared to HD patients (p≤0.035). Adiponectin levels were incrementally greater across increasing strata of PEW (p≤0.002). Leptin showed the opposite trend, with lower levels in malnourished patients and higher levels in patients with zero PEW criteria (p≤0.042). Alterations of adiponectin levels during the observation period were dependent on PEW stratum (p≤0.021) and mode of dialysis (p≤0.002), after adjustment for age, dialysis vintage, gender and fat mass index. Particularly, adiponectin levels increased over time in HD patients with ≥3 criteria for PEW, whereas adiponectin levels decreased in PD patients with ≥3 criteria for PEW throughout the study. Leptin alterations over time were not affected by dialysis mode or PEW stratification.. Our study provides evidence that increased adiponectin and decreased leptin levels are independently associated with PEW and thus, poor prognosis.

Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Anthropometry; Body Composition; Comorbidity; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Young Adult

Protein-energy wasting (PEW) contributes to mortality in hemodialysis (HD) patients. Adipokines regulate energy homeostasis and body weight. Circulating gelsolin can modulate inflammation and is correlated with HD mortality. Whether adipokines and gelsolin play important roles in PEW remains unclear. Based on the criteria proposed by the International Society of Renal Nutrition and Metabolism, we examined the associations between PEW and biomarkers (gelsolin, leptin, adiponectin, interleukin-6, tumor necrosis factor alpha [TNF-α]) in 188 stable HD patients. Patients with PEW had significantly lower serum leptin levels, and tended to have higher adiponectin, TNF-α, and lower gelsolin levels. Logistic regression analysis revealed that gelsolin, leptin, adiponectin, and blood urea nitrogen were independently associated with PEW score. Serum creatinine, TNF-α, gender, renin-angiotensin system (RAS) blockade, and lipid-lowering agents were not associated with PEW score. Patients on lipid-lowering agents had lower PEW scores and those with RAS blockade had higher PEW scores. Our study confirms that gelsolin, adiponectin, and leptin are significant associates with PEW in HD patients. Further understanding of how these factors contribute to PEW may help design novel therapeutic strategies for PEW in chronic kidney disease.

Topics: Adipokines; Aged; Biomarkers; Female; Gelsolin; Humans; Interleukin-6; Leptin; Male; Middle Aged; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

We investigated the consequences of mild maternal malnutrition in rat dams, in terms of thymocyte responses and the putative role of leptin. The young progeny of dams submitted to protein deprivation (PD) during lactation showed at 30 days of age lower body and thymus weights, significant alterations in CD4/CD8-defined T cell subsets without modifications in total thymocyte number as well as in proliferative response. Despite, the rats from PD group did not present alterations in leptin circulating levels, the expression of leptin receptor ObRb was enhanced in their thymocytes. This change was accompanied by an increase in leptin signaling response of thymocytes from PD rats, with an increase in JAK2 and STAT3 phosphorylation after leptin stimulation. Thymocytes from PD rats also presented a decreased rate of spontaneous apoptosis when compared to controls. Accordingly, higher expression of anti-apoptotic protein Bcl-2, and lower of pro-apoptotic protein Bax, with no change of pro-apoptotic Bad, and higher pro-caspase 3 content were detected in PD thymocytes. Moreover, thymocytes from PD group exhibited a constitutive higher nuclear content of p65 NF-kB associated to a lower IkB content in the cytoplasm. Finally, although there was no change in ob gene expression in PD thymocytes, a higher mRNA expression for the Ob gene was observed in the thymic microenvironment from PD animals. Taken together, the results show that mild maternal protein deprivation during lactation affects thymic homeostasis, enhancing leptin activity, which in turn protects thymocytes from apoptosis in the young progeny, with possible consequences upon the immune response of these animals in adult life.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Body Weight; Cellular Microenvironment; Diet, Protein-Restricted; Female; Gene Expression Regulation; Immunophenotyping; Janus Kinase 2; Lactation; Leptin; Male; NF-kappa B; Protein-Energy Malnutrition; Rats; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; T-Lymphocyte Subsets; Thymocytes; Thymus Gland

To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI).. Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up.. Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality.. Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.

Topics: Adult; Aged; Biomarkers; Body Composition; Body Fluid Compartments; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diabetes Complications; Female; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Muscle, Skeletal; Obesity; Proportional Hazards Models; Protein-Energy Malnutrition; Reference Values; Renal Dialysis; Reproducibility of Results; Wasting Syndrome

To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with energy homeostasis to adverse cardiovascular outcome in the HD patients.

Topics: Adult; Anorexia; Appetite; Body Composition; Cardiovascular Diseases; Circadian Rhythm; Endocrine System Diseases; Energy Metabolism; Fasting; Female; Ghrelin; Homeostasis; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Peptide YY; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency; Risk Factors

Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels are influenced by the nutritional status of the individual. We hypothesized that the consequences of ghrelin alterations in hemodialysis patients are context sensitive and dependent on the presence of protein-energy wasting (PEW). In this cross-sectional study of 217 prevalent hemodialysis patients followed for 31 months, we measured ghrelin, leptin, PEW (subjective global assessment), and C-reactive protein (an index of inflammation). Compared to patients in the middle and upper tertile of ghrelin levels, those in the lowest tertile were older, had higher leptin levels and body mass index, and presented an increased mortality risk that persisted after adjustment for age, gender, and dialysis vintage. This risk was lost after correction for comorbidities. Patients with PEW and low ghrelin values had abnormally high C-reactive protein and leptin by multivariate analysis of variance, and the highest mortality risk compared to non-PEW with high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy wasted hemodialysis patients were linked to a markedly increased cardiovascular mortality risk. Thus, since these patients were more anorectic, our results provide a clinical scenario where ghrelin therapies may be particularly useful.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proportional Hazards Models; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Sweden; Time Factors

Ghrelin is involved in the pathogenesis of protein-energy wasting (PEW), inflammation, and cardiovascular complications in end-stage renal disease (ESRD). Plasma ghrelin may prove to be a powerful biomarker of mortality in ESRD but should be considered in the context of assay specificity, other weight-regulating hormones, nutritional status, systemic inflammation, and cardiovascular risk factors. ESRD patients with PEW, systemic inflammation, and low ghrelin and high leptin concentrations have the highest mortality risk and may benefit the most from ghrelin therapy.

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors

Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis

Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis

Protein-energy malnutrition is frequently observed in patients with liver cirrhosis and is associated with their poor prognosis. Tumor necrosis factor-alpha (TNF-alpha) is elevated in those patients and may contribute to the alterations of energy metabolism. Our aim was to characterize the aberrant energy metabolism in cirrhotic patients with regard to TNF-alpha.. Twenty-four patients (mean age 65 +/- 6 y) with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twelve healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls (59 +/- 8 y). Serum levels of TNF-alpha, soluble 55-kDa TNF receptor (sTNF-R55), soluble 75-kDa TNF receptor (sTNF-R75), and leptin were determined by immunoassay. Substrate oxidation rates of carbohydrate and fat were estimated by indirect calorimetry after overnight bedrest and fasting.. In cirrhotic patients, serum levels of TNF-alpha, sTNF-R55, and sTNF-R75 were significantly higher than those in the controls and correlated with the increasing grade of disease severity as defined by Child-Pugh classification. Serum leptin concentration was not different between cirrhotics and controls but correlated with their body mass index. The decrease in substrate oxidation rate of carbohydrate and the increase in substrate oxidation rate of fat significantly correlated with serum TNF-alpha, sTNF-R55, and sTNF-R75 concentrations.. Tumor necrosis factor-alpha might be associated with the aberrant energy metabolism in patients with liver cirrhosis.

Topics: Aged; Body Mass Index; Case-Control Studies; Dietary Carbohydrates; Dietary Fats; Energy Metabolism; Female; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged; Oxidation-Reduction; Protein-Energy Malnutrition; Receptors, Tumor Necrosis Factor; Severity of Illness Index; Tumor Necrosis Factor-alpha

The goal of this study was to evaluate if maternal malnutrition during lactation could possibly program folliculogenesis, the ovarian expression of gonadotropins, leptin, and their receptors.. At parturition, dams were randomly assigned to a control group (C), with free access to a standard laboratory diet containing 23% protein, and a protein-energy-restricted group (PER), with free access to an iso-energy and protein-restricted diet containing 8% protein. After weaning, all female pups had free access to the standard laboratory diet until 90 d of age when they were euthanized in the diestrum stage.. Maternal malnutrition caused decreases in the number of primordial (C 6.60 ± 0.24, PER 5.20 ± 0.20, P = 0.01), primary (C 5.80 ± 0.66, PER 4.00 ± 0.31, P = 0.04), and Graafian (C 2.18 ± 0.29, PER 1.08 ± 0.37, P = 0.05) follicle numbers. Maternal malnutrition led to a significant decrease in the aromatase mRNA expression (C 0.536 ± 0.008, PER 0.353 ± 0.041, P = 0.01) follicle-stimulating hormone receptor (C 1.25 ± 0.17, PER 0.75 ± 0.02, P = 0.04), luteinizing hormone receptor (C 0.93 ± 0.09, PER 0.54 ± 0.10, P = 0.03), leptin (C 0.55 ± 0.03, PER 0.42 ± 0.03, P = 0.04), Ob-R (C 1.05 ± 0.12, PER 0.64 ± 0.07, P = 0.03), and Ob-Rb (C 1.34 ± 0.21, PER 0.47 ± 0.10, P = 0.02) transcripts when compared with C.. Maternal malnutrition during lactation modulates folliculogenesis and the expression of the different isoforms of leptin and gonadotropin receptors and the aromatase enzyme. This probably is a consequence of alterations in perinatal leptin concentrations that may play a crucial role in determining the occurrence of long-term metabolic changes.

Topics: Animals; Aromatase; Diet, Protein-Restricted; Female; Gene Expression Regulation; Gonadotropins; Lactation; Leptin; Maternal Nutritional Physiological Phenomena; Ovarian Follicle; Pregnancy; Protein-Energy Malnutrition; Random Allocation; Rats; Rats, Wistar; Receptors, FSH; Receptors, Leptin; Receptors, LH; RNA, Messenger

To investigate the effect of nutritional recovery with rice bran on energy balance, leptin and insulin levels.. Weaned Wistar rats were fed on a 17% (Control - C) or 0.5% (Aproteic - A) protein diet for 12d. After this, rats were kept on a C diet (C) or recovered with control (Recovered Control - RC) or control plus recovered rice bran diet (Recovered Rice Bran - RRB).. Despite the increased food intake, group A exhibited lower carcass fat associated to low serum leptin. RRB and RC groups showed lower carcass weight and energy intake and expenditure. Energy expenditure was positively associated with food intake and carcass weight. Negative correlations between HOMA-IR and energy expenditure and energy intake were observed.. Nutritional recovery with rice bran did not modify energy balance, leptin and insulin levels.

Topics: Animals; Animals, Newborn; Body Weight; Dietary Fiber; Disease Models, Animal; Eating; Energy Intake; Insulin; Leptin; Male; Oryza; Protein-Energy Malnutrition; Random Allocation; Rats; Rats, Wistar

This cross-sectional study set out to compare total and acyl ghrelin levels in children with mild chronic kidney disease (CKD) undergoing conservative treatment (n = 19) with children with end-stage renal disease (ESRD) undergoing hemodialysis (n = 24), and with healthy controls (n = 20). The relationship between ghrelin levels and parameters of renal function, nutritional status, and selective hormones were investigated. ESRD patients had higher total ghrelin levels than those with mild CKD or control individuals. However, acyl ghrelin did not differ between groups, indicating that the excess circulating ghrelin was desacylated. Since desacyl ghrelin has been shown to inhibit appetite, increased levels might contribute to protein-energy wasting in pediatric renal patients. When all 43 renal patients were combined, multiple regression analysis found age and glomerular filtration rate (GFR) to be significant negative predictors of total ghrelin. Acyl ghrelin was influenced negatively by age and positively by energy intake. Acyl to total ghrelin ratio related positively to GFR and energy intake. The results indicate that total but not acyl ghrelin is influenced by low GFR in children with CKD and suggests that ghrelin activation may be impaired in these patients. Since energy intake is a positive predictor of acyl ghrelin, the physiological control of ghrelin secretion appears to be altered in pediatric renal patients.

Topics: Acylation; Adolescent; Biomarkers; Brazil; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Energy Intake; Female; Ghrelin; Glomerular Filtration Rate; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Kidney Diseases; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Protein Processing, Post-Translational; Protein-Energy Malnutrition; Renal Dialysis; Severity of Illness Index

To study nutritional status in chronic obstructive pulmonary disease (COPD) in relation to the serum content of adipose tissue hormones.. Ninety-four patients with Stages II and III COPD and 20 gender- and age-matched healthy non-smoking volunteers were examined. Interviews, analysis of laboratory data, enzyme immunoassay, and somatometry were made.. The patients with COPD are characterized by the development of malnutrition, even in the absence of body weight loss and in the presence of normal body mass index (BMI) with predominant lean body mass (LBM) loss, normal serum concentrations of adipose tissue hormones. With more advanced COPD and a worse nutritional status, the level of leptin decreases and that of adiponectin increases. The content of adiponectins is closely related to the indicators of nutritional status, mainly to the value of body weight loss, BMI, LBM, absolute blood lymphocyte count, and degree of malnutrition. The COPD patients with emphysema show the most pronounced changes in nutritional status and higher adiponectin levels.. An integrated assessment of the degree of protein-energy malnutrition and measurement of the level of adipose tissue hormones should be made when nutritional status is studied in patients with COPD.

Topics: Adiponectin; Adipose Tissue; Body Weights and Measures; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Nutritional Status; Protein-Energy Malnutrition; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Serum levels of adipocytokines such as leptin and adiponectin are significantly elevated in patients with chronic renal failure (CRF). The effect of such adipocytokines on malnutrition in the CRF population has been of substantial interest. We sought to determine the relationship between plasma leptin and adiponectin levels and malnutrition-inflammation status in end-stage renal disease patients.. Thirty patients (15 women and 15 men; mean [+/-SD] age, 50 +/- 14 years) on hemodialysis, and 30 patients (12 women and 18 men; mean [+/-SD] age, 47 +/- 16) on continuous ambulatory peritoneal dialysis, were enrolled in this study. Adipocytokine levels were measured by enzyme-linked immunosorbent assay. Inflammatory markers, such as high-sensitivity serum C-reactive protein (hs-CRP), ferritin, and a nutritional inflammatory scoring system known as the malnutrition-inflammation score (MIS), were also measured in all patients.. Serum leptin had negative correlations with ferritin (r = -0.33, P = .016) and MIS (r = -0.39, P = .003). Adiponectin had a weak positive correlation with MIS (r = 0.26, P = .050), indicating that an increased level of serum adiponectin was associated with a worse nutritional status. Levels of hs-CRP, serum albumin, cholesterol, and triglycerides did not correlate with nutritional status.. Serum leptin concentration seems to be a marker of good nutritional status, rather than an appetite-suppressing uremic toxin, in patients with CRF. However, the positive correlation between serum adiponectin and worse nutritional-inflammatory status suggests that elevated adiponectin levels may contribute to the pathogenesis of malnutrition in such patients.

Topics: Adipokines; Adiponectin; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Peritoneal Dialysis, Continuous Ambulatory; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin

Leptin has a key role in energy homeostasis and there may be a link between leptin and insulin-like growth factor-1 (IGF-1) system. The aim of this study was to analyze the relationships between long-lasting insufficient caloric intake (marasmus), leptin and IGF-1 system.. The study group consisted of 30 marasmic children and control group included 28 healthy children. After an overnight fasting; leptin, insulin, IGF-1 and IGFBP-3 levels were measured.. Marasmic children had significantly lower body weight, height, mid-arm circumference (MAC), skinfold thickness, mean serum leptin, insulin, IGF-1 and IGFBP-3 levels compared with healthy subjects (P<0.05). Serum IGF-1 and IGFBP-3 levels were significantly correlated with insulin, MAC and height Z score in patients (P<0.05). In controls, significant positive correlations were found between BMI, IGF-1 and leptin (P<0.05).. Energy malnutrition is characterized by the important decreases in the leptin, insulin, IGF-1 and IGFBP-3 levels. Understanding details of these changes may lead to new therapeutic approaches in disease states associated with malnutrition.

Topics: Body Height; Body Mass Index; Body Weight; Female; Humans; Infant; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Protein-Energy Malnutrition

The serum leptin level is elevated in patients undergoing peritoneal dialysis (PD) and associated with a loss of lean body mass. The nutritional status of PD patients may further be worsened following peritonitis. We investigated the association between hyperleptinaemia, inflammation and malnourishment in PD-related peritonitis.. We conducted a prospective study on PD patients who developed peritonitis. Blood samples were obtained as baseline (D0) before the onset of peritonitis, and once peritonitis developed, leptin, adiponectin (ADPN) and other inflammatory markers were collected, on day 1 (D1), day 7 (D7) and day 42 (D42) of peritonitis. Patients were followed-up for any censor event or 1 year after peritonitis.. Forty-two patients with a mean age of 62.9+/-13.2 years were recruited. Fourteen (33.3%) were diabetic. The serum leptin levels increased significantly from baseline to day 1 and 7, but fell back to the premorbid state at day 42. In contrast, the ADPN level decreased from a baseline value of 15.60+/-10.4 microg/ml to 13.01+/-8.1 microg/ml on day 1 (P=0.01) but rose to 14.39+/-8.9 microg/ml on day 7 (P=0.28) and 13.87+/-7.9 microg/ml on day 42 (P=0.21). High-sensitivity C-reactive protein (hs-CRP) increased significantly from baseline to day 1, 7 and even at day 42. The lean body mass (LBM) and nutritional markers decreased significantly after peritonitis. For patients with high hs-CRP (>3.0 mg/l) at day 42, there was a higher mortality rate than for those with lower hs-CRP (<3.0 mg/l, P=0.02), even if they were in clinical remission of peritonitis.. Our study confirmed an increase in serum leptin during acute peritonitis and a prolonged course of systemic inflammation after apparent clinical remission of peritonitis. These factors related to the persistent chronic inflammation may contribute to the development of malnourishment and poor survival rate.

Topics: Adiponectin; Aged; C-Reactive Protein; Chronic Disease; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Peritonitis; Predictive Value of Tests; Prognosis; Prospective Studies; Protein-Energy Malnutrition; Tumor Necrosis Factor-alpha

The aim of this study was to investigate the oxidant/antioxidant status, paraoxonase (PON) activity and leptin levels in children with marasmic malnutrition.. Thirty marasmic children (age 14.4+/-10.3 months) and 28 control subjects were included. Plasma PON activity, total antioxidant activity (TAO), total peroxide (TPX) and leptin levels were measured.. Malnourished children had significantly lower leptin (3.6+/-1.1 vs. 11.8+/-4.5 ng/mL, P<0.001), PON activity (66.4+/-28.6 vs. 221.3+/-31.6 IU/L, P<0.001) and TAO (1.44+/-0.12 vs. 2.45+/-0.61 mmol Trolox equiv/L, P<0.001); and higher TPX (15.6+/-6.4 vs. 5.9+/-1.9 micromol/L, P<0.001) values than in controls. Significant negative correlation was found between PON and TPX (P=0.040) and positive correlation between TAO and BMI (P=0.034) in patients. No significant correlation was found between leptin and oxidant/antioxidant parameters (P>0.05).. Children with marasmic malnutrition had increased pro-oxidant and decreased antioxidant status. Extent of oxidative stress increases with malnutrition severity. Antioxidants could be given during nutritional rehabilitation.

Topics: Antioxidants; Aryldialkylphosphatase; Child, Preschool; Female; Humans; Infant; Leptin; Lipids; Male; Oxidative Stress; Peroxides; Protein-Energy Malnutrition

To investigate whether catch-up growth after maternal malnutrition would favor the development of obesity in adulthood.. Pregnant rats were submitted to protein or calorie restriction during the course of gestation. During lactation, pups were protein-restricted, normally fed, or overfed [reduced litter size, control (C) diet]. At weaning, rats were transferred to chow or to a hypercaloric diet (HCD) known to induce obesity. Body weight, food intake, blood parameters, glucose tolerance, adipocyte cellularity, and adipose factors contributing to cardiovascular disease development were measured.. Protein and calorie restriction during gestation led to growth retardation at birth. If malnutrition was prolonged throughout lactation, adult body weight was permanently reduced. However, growth-retarded offspring overfed during the suckling period underwent a rapid catch-up growth and became heavier than the normally fed Cs. Offspring of calorie-restricted rats gained more weight than those of dams fed protein-restricted diet. Feeding an HCD postnatally amplified the effect of calorie restriction, and offspring that underwent catch-up growth became more obese than Cs. The HCD was associated with hyperphagia, hyperglycemia, hyperinsulinemia, glucose intolerance, insulin resistance, and adipocyte hypertrophy. The magnitude of effects varied depending on the type and the timing of early malnutrition. The expression of genes encoding factors implicated in cardiovascular disease was also modulated differently by early malnutrition and adult obesity.. Catch-up growth immediately after early malnutrition should be a key point for the programming of obesity.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Angiotensinogen; Animals; Animals, Newborn; Body Weight; Diet; Eating; Female; Leptin; Litter Size; Male; Obesity; Plasminogen Activator Inhibitor 1; Pregnancy; Prenatal Exposure Delayed Effects; Protein-Energy Malnutrition; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Triglycerides

Protein-energy malnutrition (PEM) is a clinical problem caused by inadequate intake of one or more nutritional elements, and remains as one of the most important health problems in developing countries. The aim of this study is to determine the relationship among leptin concentrations, body weight and concentrations of some serum hormones, e.g., basal GH, IGF-1, basal cortisol and IGF-BP3, in severe malnourished children, and to determine the effects of leptin in malnourished children.. The study group consisted of 36 children diagnosed with PEM. Thirty healthy children were enrolled as the control group. After an overnight fast and before initiation of feedings, fasting venous blood samples were obtained from a forearm vein with needle technique for routine tests, and leptin, IGF-1, IGF-BP3, basal GH and cortisol levels were measured. Tests were carried out in the laboratories of the Department of Biochemistry by commercial kits.. Serum leptin levels of infants with marasmus and kwashiorkor were significantly lower than that of the controls (2.09 +/- 0.93 and 2.27 +/- 1.01, 6.82 +/- 2.28 ng/ml, respectively, P < 0.001). However, there was no significant difference between serum leptin levels in children with marasmus and those with kwashiorkor (P > 0.05). Serum IGF-1 and IGF-BP3 levels were significantly lower in malnourished children (P < 0.001, both). Also, basal GH and cortisol levels were significantly higher in malnourished children (P < 0.001, both). There was a positive correlation among serum leptin levels and IGF-1 and IGF-BP3 levels and also a negative correlation among serum leptin levels and basal GH and cortisol levels in children diagnosed with marasmus or kwashiorkor and the control group.. The decrease of energy intake and adipose tissue and serum IGF-1 levels in children with PEM may result in decrease of leptin secretion. Decrease in serum leptin levels may initiate food intake by increasing appetite and stimulating the secretion of cortisol and GH that might increase energy expenditure through an autocrine mechanism. Moreover, serum leptin level may be an important signal to reflect the metabolism of children with PEM.

Topics: Anthropometry; Appetite; Case-Control Studies; Female; Growth Hormone; Humans; Hydrocortisone; Infant; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Kwashiorkor; Leptin; Male; Protein-Energy Malnutrition

Leptin and dyslipidemia are risk factors for cardiovascular disease. We measured leptin and lipid levels, and examined whether there is an effect of leptin on lipid profile in marasmic children.. Fifty children (25 marasmic, 25 healthy) aged between 0.3 and 2.5 years were evaluated. Leptin levels were compared with lipid profile in marasmic and healthy children. The relationships between leptin and sex, body mass index and lipid profile were investigated in marasmic children.. In the marasmic group, body mass index, leptin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p < 0.0001, p < 0.0001, p = 0.01, respectively), and triglyceride levels higher than in the control group. In females, leptin was correlated positively with high-density lipoprotein cholesterol (p = 0.002), and inversely correlated with the triglyceride level (p = 0.003). In males, a positive correlation was found between leptin and low-density lipoprotein cholesterol (p = 0.026). In female patients, body mass index, leptin and high-density lipoprotein cholesterol levels were lower (p < 0.0001, for all) when compared to their female controls. In male patients, body mass index, leptin, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p = 0.031, p = 0.002, p = 0.017, respectively) than those in their male controls.. As a result, we found low leptin (an independent cardiovascular risk factor) levels, but dyslipidemia in our marasmic patients. Dyslipidemia may be a risk factor for cardiovascular complications in marasmic children in the future.

Topics: Cardiovascular Diseases; Case-Control Studies; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Infant; Leptin; Lipids; Male; Protein-Energy Malnutrition; Risk Factors; Sex Factors; Triglycerides

Recent studies have shown that leptin receptor is expressed in human and rat pituitary glands. The expression of leptin receptor in rats whose dams were malnourished during lactation has not been previously reported.. We examined leptin receptor expression in the pituitary gland of adult rats whose dams were assigned to one of the following groups during lactation: control diet, protein-restricted diet (8% protein), or energy-restricted diet (the control diet fed in restricted quantities that were calculated according to the mean ingestion of the protein-restricted group). After weaning, all pups had free access to the control diet until they reached adult age, at which time leptin receptor expression in the pituitary was analyzed by immunohistochemistry.. Adult animals from protein- and energy-restricted dams had a higher expression of leptin receptor in pituitary tissue, normal serum leptin concentrations, higher serum tri-iodothyronine concentrations, and lower thyroid-stimulating hormone concentrations than did the control rats.. In the fed state, leptin has a stimulatory effect on release of thyroid-stimulating hormone. The higher expression of leptin receptor in the pituitary of animals from protein- and energy-restricted dams may suggest a postreceptor failure in leptin action. This higher receptor expression may have allowed a greater inhibition of release of thyroid-stimulating hormone.

Topics: Animals; Animals, Suckling; Diet, Protein-Restricted; Diet, Reducing; Female; Immunohistochemistry; Lactation; Leptin; Pituitary Gland; Protein-Energy Malnutrition; Random Allocation; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Leptin; Thyrotropin

The aim of the present study was to clarify the relationship between nutritional anthropometric parameters and serum leptin concentrations in otherwise healthy children with mild-to-moderate protein-energy malnutrition (PEM) secondary to inadequate energy intake.. Eighty-one otherwise healthy children with poor appetite and inadequate energy intake were enrolled in the study. The anthropometric values were evaluated in all subjects. Fasting serum leptin concentrations were assessed.. Of the 81 otherwise healthy children, 30 were found to have mild-to-moderate PEM. The control group consisted of 51 healthy children who had normal anthropometric values, even though they had inadequate energy intake. There was a significant difference in serum leptin concentrations between the two groups (P < 0.01). Furthermore, there was a positive correlation between mean serum leptin concentrations and percentage of standard weight for height in the patient and the control group (P < 0.05). Multiple linear regression analysis indicated that percentage of standard BMI was the best predictor for serum leptin concentrations (P < 0.05).. In addition to BMI, percentage of standard weight for height is a valuable nutritional anthropometric parameter for serum leptin concentrations in PEM and inadequate energy intake. However in the present study, percentage of standard BMI was the best predictor for serum leptin concentrations. Serum leptin concentrations are low not only in severe PEM, but also in children with mild-to-moderate PEM without chronic disease.

Topics: Body Height; Body Weight; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Leptin; Male; Protein-Energy Malnutrition; Skinfold Thickness

Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for 58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy children ( P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin concentration was 15 microU/ml (1.63-45.80) and did not correlate with leptin and IGF-I levels. In conclusion, the results of this study confirm the presence of high circulating plasma leptin levels, which may be one of the many factors involved in the pathogenesis of the malnutrition in children on hemodialysis.

Topics: Adolescent; Anthropometry; Arm; Biomarkers; Blood Urea Nitrogen; Body Mass Index; Body Weight; Child; Creatinine; Female; Humans; Insulin; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Protein-Energy Malnutrition; Renal Dialysis; Skinfold Thickness

Although it is well known that leptin reflects body fat content in adults, the regulation of leptin levels during childhood malnutrition is poorly understood. Insulin-like growth factor I (IGF-I) and the IGF-binding proteins (IGFBPs) may play important roles in the regulation of body composition. We investigated the relation between leptin, IGF-I, and IGFBPs in children with protein-energy malnutrition (PEM; before and after recovering 10% of their initial body weights) in comparison with well-nourished children.. Fifteen PEM and 16 healthy children were studied on admission and after 10% weight gains in the malnourished group. Leptin was measured with radioimmunoassay, IGF-I and IGFBPs were measured with immunoradiometric assay.. Patients with PEM had a significantly lower body mass index and percentage of body fat than did the control children. Before weight gain, leptin, IGF-I, and IGFBP-3 were significantly lower and IGFBP-1 was elevated in the malnourished group compared with the control group. Among PEM patients, after 10% weight gains, the levels of leptin, IGF-I, and IGFBP-3 were significantly higher and IGFBP-1 significantly lower compared with the control group. Leptin correlated significantly with IGF-I in the normal children (r(s) = 0.86, P < 0.005). On admission, no correlation was observed between leptin and IGF-I (r(s) = 0.08, P < 0.16) and between leptin and IGFBP-3 (r(s) = 0.02, P < 0.27) in the malnourished group, but those levels improved after 10% recovery of their body weights (r(s) = 0.47, P < 0.002 and r(s) = 0.42, P < 0.005, respectively). In the PEM group, IGF-I correlated significantly with IGFBP-3 when the children gained weight (before: r(s) = 0.006, P < 0.31; after: r(s) = 0.32, P < 0.01). Our study showed results similar to those of anorexia nervosa studies, but the normalization of study variables was obtained in considerable less time for the same weight gain.. The main finding of this study was that, after refeeding with only a 10% weight gain, the PEM children normalized their leptin, IGF-I, and IGFBP-3 levels. These results provide evidence that leptin can function as link between this hormonal response and improved nutrition status.

Topics: Body Composition; Child, Preschool; Female; Humans; Infant; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Protein-Energy Malnutrition; Radioimmunoassay; Weight Gain

Maternal low-protein malnutrition during gestation and lactation (LP) is an animal model frequently used for the investigation of long-term deleterious consequences of perinatal growth retardation. Hypothalamic neuropeptides are decisively involved in the central nervous regulation of body weight and metabolism. We investigated neuropeptide Y (NPY) in distinct hypothalamic nuclei in the offspring of LP mother rats at the end of the critical hypothalamic differentiation period (20th day of life). Weanling LP offspring were underweight (P< 0.001) and hypoinsulinaemic (P< 0.05), while leptin levels were unchanged. NPY was significantly increased in the paraventricular hypothalamic nucleus (PVN) (P< 0.01) and lateral hypothalamic area (P< 0.05) in LP offspring. In contrast, NPY was unchanged in the ventromedial hypothalamic nucleus (VMN). These observations indicate a leptin-independent stimulation of the orexigenic ARC-PVN axis in undernourished LP rats at weaning. Furthermore a disturbed NPYergic regulation of the VMN is suggested, possibly contributing to alterations of the hypothalamic regulation of body weight and metabolism in LP offspring during life.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Female; Hypothalamic Area, Lateral; Hypothalamus; Insulin; Leptin; Male; Median Eminence; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein-Energy Malnutrition; Rats; Rats, Wistar; Ventromedial Hypothalamic Nucleus; Weaning

The dysregulation of the immune and inflammatory systems observed in protein-energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium ionophore A23187-induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in isolated granulocyte suspensions.. Case-control study.. A university-affiliated acute care hospital in urban Stockholm.. Fourteen severely malnourished elderly subjects with stable non-malignant disorders (age 74 +/- 1 years, mean +/- SEM) and 12 healthy age-matched controls were examined.. Leukotrienes were analysed by high-performance liquid chromatography. Body mass index (BMI, kg m-2) and delayed cutaneous hypersensitivity (DCH) reaction were determined.. BMI was 16. 5 +/- 0.5 and 26.2 +/- 0.9 kg m-2 (mean +/- SE) in the malnourished group and controls (P < 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5 mm in controls (P < 0.001). LTC4 generation in granulocytes from PEM patients was half of that of controls (9.1 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL-1, P < 0.05) when cells were stimulated with 0.2 micromol L-1 of A23187, and 13.7 +/- 2.5 and 27.2 +/- 7.5 pmol mL-1, respectively (NS), upon stimulation with 1.0 micromol L-1 of A23187. LTB4 production in PEM patients and controls did not differ at any of the two calcium ionophore concentrations. LTC4 production correlated with BMI (r = 0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or LTC4 production.. Protein-energy malnutrition is accompanied by perturbation of leukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.

Topics: Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Chromatography, High Pressure Liquid; Chronic Disease; Female; Granulocytes; Humans; Hypersensitivity, Delayed; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Leukotriene B4; Leukotriene C4; Male; Orosomucoid; Protein-Energy Malnutrition; Skin; Superoxides

Circulating leptin, insulin, insulin-like growth factor-I (IGF-I), cortisol, and albumin concentrations and the growth hormone (GH) response to provocation were measured in 30 children with severe protein-energy malnutrition (PEM), 20 with marasmus and 10 with kwashiorkor, as well as 10 age-matched normal children (body mass index [BMI] >50th and <90th percentile for age and sex) and 10 prepubertal obese children (BMI >95th percentile for age and sex). Patients with PEM had a significantly lower BMI, midarm circumference (MAC), and skinfold thickness (SFT) compared with the age-matched control group. Basal cortisol and GH concentrations were significantly higher in the malnourished groups versus controls. Leptin and IGF-I were significantly lower in the marasmic and kwashiorkor groups versus normal children. Fasting insulin levels were significantly decreased in the kwashiorkor group compared with marasmic and normal children. The BMI correlated significantly with leptin (r = .77, P < .001), basal insulin (r = .61, P < .001), and IGF-I (r = .77, P < .001) and negatively with basal GH (r = -.52, P < .001). These findings suggest that during prolonged nutritional deprivation, the decreased energy intake, diminished subcutaneous fat mass, and declining insulin (and possibly IGF-I) concentration suppress leptin production. In support of this view, serum leptin levels were positively correlated with triceps, scapular, and abdominal SFT (r = .763, .75, and .744, respectively, P < .0001) in all of the children. Moreover, basal insulin and circulating IGF-I were correlated significantly with leptin concentrations (r = .47 and .62, respectively, P < .001). Basal levels of cortisol and GH were significantly elevated in the 2 groups with severe PEM. It is suggested that low leptin levels can stimulate the hypothalamic-pituitary-adrenal (HPA) axis and possibly the hypothalamic-pituitary-GH axis to maintain the high cortisol and GH levels necessary for effective lipolysis to ensure a fuel (fatty acids) supply for the metabolism of brain and peripheral tissue during nutritional deprivation. In summary, during prolonged PEM, the decreased synthesis of IGF-I and the low level of insulin and/or its diminished effect due to an insulin-resistant status in the presence of high circulating GH and cortisol levels ensure substrate diversion away from growth toward metabolic homeostasis. Leptin appears to be an important signal in the process of metabolic/endocrine adaptation to

Topics: Child, Preschool; Endocrine Glands; Female; Growth; Human Growth Hormone; Humans; Infant; Insulin-Like Growth Factor I; Leptin; Lipoproteins, VLDL; Male; Protein-Energy Malnutrition; Triglycerides

Serum leptin levels are increased in chronic renal failure (CRF) and may potentially contribute to protein malnutrition in this disorder.. Following a cross-sectional design, we performed a nutritional survey in a wide sample of uremic patients treated conservatively (n = 87), with peritoneal dialysis (n = 71) and with hemodialysis (n = 53). Then, we analyzed the correlation between serum leptin levels and markers of protein malnutrition. We used a multivariate approach, taking into consideration the confounding effect of other factors on the correlation between hyperleptinemia and protein malnutrition.. Both univariate and multivariate analysis disclosed a poor correlation between hyperleptinemia and markers of protein malnutrition. In fact, there were trends to a positive correlation between leptinemia and body protein stores, as estimated from the scrutinized markers. Persistence of the basic correlation between general intake, fat mass and leptin in CRF could partially explain these findings, but neither a negative correlation between leptin levels nor protein nutritional state could be disclosed after controlling for this factor.. Our results do not support a first-line role for hyperleptinemia in the genesis of protein malnutrition of uremia.

Topics: Adult; Aged; Biomarkers; Body Mass Index; Female; Humans; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis, Continuous Ambulatory; Prealbumin; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Transferrin; Uremia

Leptin is a protein hormone produced by adipocytes. Its serum concentrations in the most of cases positively correlate with total body fat content. Serum leptin levels are increased in obese in comparison with lean subjects. Leptin levels in females are two or three times higher than in body mass index and age-matched males. The aim of our study was to investigate the serum leptin concentrations in females with protein-caloric malnutrition of various aetiology, the relationship between leptin levels and biochemical nutritional parameters and to compare the values with those of age-matched control group. Totally 12 patients with malnutrition of various aetiology and 14 control age-matched healthy subjects were included into the study. It was found that serum leptin levels were significantly decreased in malnutrition group in comparison with control group (3.09 +/- 1.33 ng.ml-1 vs 9.42 +/- 2.76 ng.,l-1, p < 0.05). A significant decrease in body mass index, serum total protein, albumin, prealbumin, cholesterol and triglycerides concentration was also found in malnutrition in comparison with control group. While a strong positive correlation between leptin concentrations and body mass index was found in control group (r = 0.72, p < 0.05), no statistically significant relation between leptin and body mass index was observed in malnutrition group. Furthermore, no significant relationship was found between serum leptin levels and serum total protein, albumin, prealbumin, cholesterol and triglycerides neither in control or in malnutrition group. We conclude that serum leptin levels in patients with malnutrition are significantly decreased in comparison with age-matched healthy control subjects. The loss of positive correlation between leptin and body mass index in malnutrition group is explainable by the changes of body composition in patient with malnutrition. The body mass index value in these patients reflects the total body fat content less precisely than in healthy controls.

Topics: Biomarkers; Body Mass Index; Female; Humans; Leptin; Middle Aged; Nutritional Status; Protein-Energy Malnutrition

To evaluate serum leptin, a fat cell-derived protein, levels in relation to the malnutrition often observed in chronic disease.. A comparison of circulating leptin concentrations in malnourished chronically ill elderly and in age-matched controls.. A university-affiliated teaching hospital in Stockholm, Sweden.. Nineteen protein-energy malnourished elderly patients (74 +/- 1 years) with various chronic nonmalignant diseases and 18 healthy controls (72 +/- 1 years).. Serum leptin levels measured by radioimmunoassay technique, nutritional status as expressed by body mass index (kg m[-2]), triceps skin fold, arm muscle circumference and serum albumin, and serum orosomucoid concentrations indicating inflammatory status.. Patients and controls displayed body mass indexes of 17.4 +/- 0.7 and 25.0 +/- 1.1 (P < 0.001), respectively. Triceps skin fold (TSF) measurements revealed a pronounced fat depletion in the patients, being 8.5 +/- 0.9 and 22.3 +/- 1.5 mm (P < 0.001) in female and 6.1 +/- 0.7 and 10.8 +/- 0.8 mm (P < 0.001) in male patients and controls, respectively. Patient serum leptin concentrations were less than half of the corresponding concentrations in the controls, 4.3 +/- 1.1 and 9.3 +/- 1.3 ng mL(-1)(P < 0.01), respectively. The highest leptin concentrations were registered in female controls, 12.1 +/- 1.6 ng mL(-1). The serum leptin levels in the controls correlated with TSF (r = 0.74: P < 0.001). No such correlation was found in the patients.. Serum leptin levels were low and did not seem to be directly associated with fat and muscle depletion in elderly patients with chronic illness, whereas they appeared to be positively correlated to body fat in healthy elderly.

Topics: Adipose Tissue; Aged; Body Mass Index; Case-Control Studies; Chronic Disease; Female; Humans; Leptin; Male; Nutritional Status; Orosomucoid; Protein-Energy Malnutrition; Proteins; Radioimmunoassay; Serum Albumin