Lower Serum Leptin Levels Research Articles

Cold and Hungry: Heterothermy Is Associated with Low Leptin Levels in a Bulk Grazer during a Drought.

AbstractReduced energy intake can compromise the ability of a mammal to maintain body temperature within a narrow 24-h range, leading to heterothermy. To investigate the main drivers of heterothermy in a bulk grazer, we compared abdominal temperature, body mass, body condition index, and serum leptin levels in 11 subadult Cape buffalo (Syncerus caffer caffer) during a drought year and a nondrought year. Low food availability during the drought year (as indexed by grass biomass, satellite imagery of vegetation greenness, and fecal chlorophyll) resulted in lower body condition index, lower body mass relative to that expected for an equivalent-aged buffalo, and lower leptin levels. The range of 24-h body temperature rhythm was 2°C during the nondrought year and more than double that during the drought year, and this was caused primarily by a lower minimum 24-h body temperature rhythm during the cool dry winter months. After rain fell and vegetation greenness increased, the minimum 24-h body temperature rhythm increased, and the range of 24-h body temperature rhythm was smaller than 2°C. In order of importance, poor body condition, low minimum 24-h air temperature, and low serum leptin levels were the best predictors of the increase in the range of 24-h body temperature rhythm. While the thermoregulatory role of leptin is not fully understood, the association between range of 24-h body temperature rhythm and serum leptin levels provides clues about the underlying mechanism behind the increased heterothermy in large mammals facing food restriction.

Association of Serum Leptin With Body Mass Index in Gallbladder Cancer Patients: A Pilot Study.

Leptin has been proposed to be a link between obesity and the increased incidence of various cancers like breast cancer, colon cancer, gastric cancer, etc. The role of leptin in gallbladder cancer is largely undetermined. Moreover, no study has evaluated serum leptin levels and their correlation with clinicopathological characteristics and serum tumour markers in gallbladder cancer (GBC). Therefore, the present study was planned. A cross-sectional study was conducted in a tertiary care hospital in Northern India after obtaining ethical approval from the institution. Forty GBC patients staged as per American Joint Committee on Cancer (AJCC) 8th staging systemwere recruited along with 40 healthy controls. Serum leptin was assayed by sandwich enzyme-linked immunosorbent assay (ELISA) and tumour markers (CA19-9, CEA and CA125) by Chemiluminescence.ROC, Mann Whitney U test, Linear regression and Spearman correlation was performed using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY). BMI was also assessed for both groups. Median BMI for GBC patients was 19.46 (IQR 17.61-22.36). Median serum leptin levels were significantly lower (2.09 (IQR 1.01-7.76) ng/mL) in GBC patients as compared to controls (12.32 (IQR 10.50-14.72) ng/mL). AUC was 0.84 with 100% sensitivity and 75% specificity at 7.57 ng/mL.Serum leptin was not associated with cancer stage, resectability, metastasis, liver infiltration, or tumour markers on linear regression (p=0.74, adjusted R square = -0.07). A significant positive correlation was found between BMI and serum leptin in GBC patients (p=0.00). Lower BMI and relatively lean presentation of GBC patients may account for low serum leptin levels.

Association between Maternal Serum Leptin Level and Preterm Birth among Parturients in Lagos, Nigeria

Background: Preterm birth is one of the major causes of neonatal morbidity and mortality worldwide. The association between occurrence of preterm birth and biomarkers measured in the maternal serum maybe helpful in predicting preterm birth especially in low resource settings. Aim: We aimed to examine the association between maternal serum leptin level and occurrence of preterm birth. Materials and Methods: This was an analytical cross-sectional study of women with preterm and term births in Lagos, Nigeria. One hundred and ninety women comprising of 95 women with preterm and term births respectively recruited. Maternal serum leptin levels were determined using Enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed by Stata version 16 (StataCorp, USA) statistical software with significance level set at p-value <0.05. Results: The mean serum leptin levels were significantly lower in women with preterm delivery compared to women with term delivery (1.48 ng/ml ± 0.72 vs. 1.75 ng/ml ± 0.67, p-value=0.007). On further analysis, women with very preterm birth had significantly lower serum leptin levels compared with women with moderate to late preterm and term births (1.28 ± 0.73 vs 1.55 ± 0.70 vs 1.75ng/ml ± 0.67, p-value=0.006). There was 57% reduction in the odds of having preterm delivery for every unit increase in serum leptin level on multivariate analysis (adjusted OR: 0.43, 95%CI: 0.26 – 0.71, P-value=0.001). Conclusion: Serum leptin concentration was significantly lower in women who had preterm births compared to women who had term births. Longitudinal studies are required to determine the predictive value of maternal serum leptin level with regards to preterm birth.

Elevated serum leptin levels are associated with lower renal function among middle-aged and elderly adults in Taiwan, a community-based, cross-sectional study.

Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail. The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia. In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia. According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

Clonal hematopoiesis in men living with HIV and association with subclinical atherosclerosis.

People with HIV (PWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of clonal hematopoiesis and its association with chronic inflammation and CVD in PWH. Cross-sectional study utilizing archived specimens and data from 118 men (86 PWH and 32 HIV-uninfected) from the Baltimore-Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary computed tomography angiography (CTA) and measurement of 34 serologic inflammatory biomarkers. Clonal hematopoiesis was assessed on peripheral blood mononuclear cells utilizing targeted error-corrected next generation sequencing (NGS) focused on 92 genes frequently mutated in hematologic malignancies. Clinical and laboratory data were obtained from the MACS database. Clonal hematopoiesis with a variant allele frequency (VAF) greater than 1% was significantly more common in PWH [20/86 (23.3%)] than in HIV-uninfected men [2/32 (6.3%)] ( P = 0.035). PWH with clonal hematopoiesis (VAF > 1%) were more likely to have coronary artery stenosis of at least 50% than those without clonal hematopoiesis [6/20 (30%) vs. 6/64 (9%); P = 0.021]. Presence of clonal hematopoiesis was not significantly associated with serological inflammatory markers, except for significantly lower serum leptin levels; this was not significant after adjustment for abdominal or thigh subcutaneous fat area. Clonal hematopoiesis was more common in PWH and among PWH was associated with the extent of coronary artery disease. Larger studies are needed to further examine the biological and clinical consequences of clonal hematopoiesis in PWH.

Increased exploration and hyperlocomotion in a cigarette smoke and LPS-induced murine model of COPD: linking pulmonary and systemic inflammation with the brain.

Brain-related comorbidities are frequently observed in chronic obstructive pulmonary disease (COPD) and are related to increased disease progression and mortality. To date, it is unclear which mechanisms are involved in the development of brain-related problems in COPD. In this study, a cigarette smoke and lipopolysaccharide (LPS) exposure murine model was used to induce COPD-like features and assess the impact on brain and behavior. Mice were daily exposed to cigarette smoke for 72 days, except for days 42, 52, and 62, on which mice were intratracheally exposed to the bacterial trigger LPS. Emphysema and pulmonary inflammation as well as behavior and brain pathology were assessed. Cigarette smoke-exposed mice showed increased alveolar enlargement and numbers of macrophages and neutrophils in bronchoalveolar lavage. Cigarette smoke exposure resulted in lower body weight, which was accompanied by lower serum leptin levels, more time spent in the inner zone of the open field, and decreased claudin-5 and occludin protein expression levels in brain microvessels. Combined cigarette smoke and LPS exposure resulted in increased locomotion and elevated microglial activation in the hippocampus of the brain. These novel findings show that systemic inflammation observed after combined cigarette smoke and LPS exposure in this COPD model is associated with increased exploratory behavior. Findings suggest that neuroinflammation is present in the brain area involved in cognitive functioning and that blood-brain barrier integrity is compromised. These findings can contribute to our knowledge about possible processes involved in brain-related comorbidities in COPD, which is valuable for optimizing and developing therapy strategies.

Factors Associated with Long-Term Survival in Maintenance Hemodialysis Patients: A 5-Year Prospective Follow-Up Study.

ObjectivesIn addition to an increase in the prevalence of dialysis treatments for end-stage renal disease worldwide, the mortality rates among patients on maintenance hemodialysis remain higher than that of the general population. This study aims to evaluate factors associated with long-term survival in stable maintenance hemodialysis patients.MethodsA total of 100 patients initiating hemodialysis by February 2013 were included in this prospective cross-sectional 5-year follow-up study. Data on patient demographics, anthropometric-nutritional parameters, systolic and diastolic blood pressure levels, and hemodialysis parameters, including etiology of kidney failure, hemodialysis duration, peritoneal dialysis history, relative interdialytic weight gain (RIDWG), and Kt/V, were recorded.ResultsOverall 5-year survival rate was 56.6%. The 5-year survival rate was higher in patients with younger age (71.4% below median vs. 42.0% above median, p=0.023), lower systolic (63.3 vs. 50%, respectively, p=0.005) and diastolic (62.5 vs. 51.0%, respectively, p=0.02) blood pressure levels, higher Kt/V (46.9 vs. 66.0%, respectively, p=0.044), lower RIDWG (54.0 vs. 32.7%, respectively, p=0.026), and lower serum leptin levels (63.3 vs. 50.0%, respectively, p=0.047). Cox-regression analysis revealed that only systolic blood pressure (B = 1.081, 95% CI, 0.152 to 0.756, p=0.08) was a significant risk factor for poor survival.ConclusionOur findings revealed pre-dialysis systolic blood pressure as the sole risk factor for poor long-term survival in stable maintenance hemodialysis patients. Malnutrition-inflammation, measures of nutrition, inflammation, and anemia had no significant impact on long-term survival.

Alterations of Serum Leptin Levels in Patients with Autoimmune Thyroid Disorders.

Background: Thyroid dysfunction is accompanied with significant metabolic alterations that affect body weight, appetite, and energy expenditure, as well as lipid and carbohydrate metabolism. Leptin, an adipokine produced by adipocytes, regulates food intake and energy storage. Thyroid hormones and leptin share some physiological effects. Changes in leptin have been shown in patients with dysfunction of the thyroid; however, the results are contradictory. The aim of this study was to evaluate the circulating levels of leptin in patients with Graves disease (GD) and Hashimoto thyroiditis (HT) before and after normalization of thyroid function compared with the control group. Methods: Newly diagnosed adult patients with GD, HT, and healthy euthyroid controls were recruited. Various clinical and biochemical parameters, including thyroid function tests and serum leptin level, were assessed before and after treatment and compared between groups. Results: Data from 56 patients with HT, 54 patients with GD, and 54 healthy controls were analyzed. Serum leptin levels of patients with HT (30.96 ± 3.88 ng/mL) were found to be significantly higher than the controls (22.35 ± 4.72 ng/mL) (p<0.001), whereas patients with Graves had lower serum leptin levels (14 ± 4.54 ng/mL) (p<0.001). In patients with HT, serum leptin levels showed a significant decrease after treatment (31 vs 27 ng/mL; p<0.001), while in patients with GD, leptin increased significantly after treatment (14 vs 17 ng/mL; p<0.001). Conclusion The present study showed that serum leptin levels increased in patients with HT and decreased in those with GD than the control group. However, after treatment, leptin decreased in the Hashimoto group and increased in the Graves group, although it was still significantly different from the control group.

Hypothalamic Leptin Gene Therapy and Caloric Restriction Have Differential Effects on Energy Intake and Energy Partitioning in Adult Female Rats

ObjectivesWeight gain during middle age is associated with several chronic diseases. Dieting is a common but often ineffective long-term strategy for stabilizing body weight at optimal levels for health. Similar to humans, middle-aged rats exhibit progressive weight gain and are a useful model for evaluating strategies for controlling weight. The adipokine leptin is an important regulator of appetite and energy expenditure but peripheral hyperleptinemia is associated with leptin resistance and may contribute to chronic inflammation. Here we compared the effects of increasing leptin levels selectively in the hypothalamus using gene therapy with conventional caloric restriction (CR) on weight gain, food consumption, serum leptin, abdominal white adipose tissue, and bone marrow adipose tissue in nine-month-old female rats. MethodsRats (n = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with adeno-associated virus encoding a recombinant rat gene for leptin (rAAV-lep) and maintained on standard rat chow for 18 weeks. A control group (n = 15) was calorically restricted (CR) to match the weight of the rAAV-lep group. ResultsBoth approaches were effective in preventing weight gain. However, rAAV-lep rats consumed 16% more food and had higher brown adipose tissue Ucp-1 mRNA expression than CR rats. Additionally, compared to CR rats, rAAV-lep rats had lower abdominal white adipose tissue mass, lower serum leptin levels, and lower bone marrow adiposity. ConclusionsHypothalamic leptin gene therapy and CR, while equally effective in preventing weight gain, differ in their effects on energy intake, expenditure and body composition. Our findings suggest that increasing hypothalamic leptin levels has advantages (e.g., desirable body composition and unrestricted food intake) over conventional CR as a strategy for preventing age-related weight gain. Funding SourcesNIH AR060913.

Association of Circulating Nutritional Markers, Diets, Lifestyles, Workplace and Environmental Exposures With Nasopharyngeal Carcinoma In Malaysia

Abstract Objectives This case-control study was conducted to determine the association between circulating nutritional markers, diet, lifestyle factors, workplace and environmental exposure with risk and survival of NPC in the search for markers to predict risk and prognosticate survival for this disease. Methods A total of 300 histologically confirmed NPC cases and 300 matched (age, gender, ethnicity) cancer-free controls were recruited from two local hospitals. An interviewer-administrated questionnaire was used to collect data. Anthropometry measurements were taken directly after interview. The fasting blood sample was collected by a trained and qualified paramedic from respective hospitals and analysed using relevant analysis in the laboratory. Clinical characteristics were obtained from patients’ medical records. Results Vigorous physical activity (AOR = 1.58, 95% CI = 1.09, 2.31), ex-smoking habit (AOR (quitted ≤ 2 years) = 4.69, 95% CI = 1.63, 13.5) and alcohol consumption (AOR (once a week) = 3.10, 95% CI = 1.22, 7.91) significantly increased the risk of NPC. A medium consumption of high-protein dietary pattern was protective against NPC risk (AOR (Q2 vs Q1) = 0.44, 95% CI = 0.25, 0.76), while a high consumption of high-salted and processed food dietary pattern increased the risk of NPC (AOR (Q4 vs. Q1) = 9.75, 95% CI = 4.66, 20.38). Workplace exposures to leather, cloth, textiles or carpet and dust, smoke, fumes or gases significantly increased the risk of NPC. Environmental exposure to disinfectants or biocides significantly increased the risk of NPC. The overall survival of NPC was 63.7% with 79.3% complete remission. Advanced NPC stage (AOR (Stage 4C) = 5.64, 95% CI = 1.13, 28.2), treatment with chemotherapy alone (AOR = 5.58, 95% CI = 2.30, 13.50) and low serum leptin level (AOR (Q1 vs. Q4) = 9.61, 95% CI = 3.36, 27.47) significantly increased risk of NPC mortality. Conclusions In conclusion, the generation of risk models in this study based on these factors would not only increase understanding of NPC aetiology, but could potentially contribute to planning and implementation of clinical and public health interventions. Funding Sources This study was funded by Science Fund, Ministry of Science, Technology, and Innovation, Malaysia.

Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes.

Obesity is an established risk factor for breast cancer in post-menopausal women, being associated with elevated serum levels of leptin. Although overweight is a common condition in cat, the role of leptin and its receptor in feline mammary carcinoma remains unsettled. In this study, serum leptin and leptin receptor (ObR) levels were investigated in 58 cats with mammary carcinoma and compared with those of healthy animals, as were the expression levels of leptin and ObR in tumor tissues. The results showed that the Free Leptin Index is significantly decreased in cats with mammary carcinoma (p = 0.0006), particularly in those with luminal B and HER2-positive tumors, and that these animals also present significantly lower serum leptin levels (p < 0.0001 and p < 0.005, respectively). Interestingly, ulcerating tumors (p = 0.0005) and shorter disease-free survival (p = 0.0217) were associated to serum leptin levels above 4.17 pg/mL. In contrast, elevated serum ObR levels were found in all cats with mammary carcinoma (p < 0.0001), with levels above 16.89 ng/mL being associated with smaller tumors (p = 0.0118), estrogen receptor negative status (p = 0.0291) and increased serum levels of CTLA-4 (p = 0.0056), TNF-α (p = 0.0025), PD-1 (p = 0.0023), and PD-L1 (p = 0.0002). In tumor samples, leptin is overexpressed in luminal B and triple-negative carcinomas (p = 0.0046), whereas ObR is found to be overexpressed in luminal B tumors (p = 0.0425). Altogether, our results support the hypothesis that serum levels of leptin and ObR can be used as biomarkers of specific feline mammary carcinoma subtypes, and suggests the use of leptin antagonists as a therapeutic tool, reinforcing the utility of the cat as a cancer model.

Protective effect of pharmacological castration on metabolic perturbations and cardiovascular disease in the hyperglycemic male ApoE-/-:Ins2+/Akita mouse model.

Unlike in other mouse models of atherogenesis, it has recently been suggested that orchiectomy plays a role in accelerating atherosclerosis and inhibiting the progression of cardiovascular disease in the ApoE-/-:Ins2+/Akita mouse model of hyperglycemia. Androgen-deprivation therapy (ADT) is a common treatment for prostate cancer, a population with high prevalence of cardiovascular disease and its risk factors. Our objectives were to test and further characterize the effects of pharmacological castration which is currently the acceptable modality to deliver ADT in the clinic. Male ApoE-/-:Ins2+/Akita mice received one of three modes of ADT (gonadotropin-releasing hormone (GnRH)-antagonist (degarelix), GnRH-agonist (leuprolide), or bilateral orchiectomy) and were compared to corresponding untreated control mice (n = 9-13/group). Mice were followed for 5 months. Body weight, fasting blood glucose, glucose tolerance, serum C-peptide, leptin, and testosterone levels along with atherosclerotic aortic plaque size and characteristics were determined. In a separate experiment, the survival of mice, untreated and on ADT, was determined. Castration was achieved for all three modes of ADT. However, degarelix-treated mice gained significantly less weight, had lower serum leptin levels and systolic blood pressure compared to orchiectomy and leuprolide-treated mice. ADT improved dysglycemia and atherosclerotic burden. GnRH-antagonist significantly improved survival compared to GnRH-agonist but not compared to orchiectomy. Further characterization of the ApoE-/-:Ins2+/Akita mouse model confirms that pharmacological ADT ameliorated metabolic syndrome and cardiovascular complications. Improved dysglycemia and atherosclerosis associated with increased survival which was longest after degarelix followed by orchiectomy.

Relationship of dietary and serum zinc and leptin levels with protein energy wasting in haemodialysis patients.

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 19-65years who received haemodialysis treatment three times a week for at least 1year. 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.

TREATMENT RESPONSE PREDICTION IN PATIENTS WITH RHEUMATOID ARTHRITIS. Review

Relevance. A variety of targeted therapies for rheumatoid arthritis (RA) treatment exist. Therefore, reliable predictors are needed that could be used to accurately predict the efficacy or inefficacy of these therapies in individual patients. This could allow clinicians to improve diagnosis and prognosis, to make the treatment personalized and to reduce healthcare expenses.&#x0D; Objectives: to analyze and systemize the predictors of response to treatment in patients with RA.&#x0D; Materials and Methods. We analyzed the recently discovered predictors of treatment response in RA patients using papers cited on PubMed, Lilacs, and EMBASE databases from Jan 2005 until Jan 2020. Predictive factors were grouped into four categories: methotrexate (MTX)-treated RA, tumor necrosis factor (TNF)-α inhibitors-treated RA, interleukin (IL)-6 inhibitors-treated RA, and rituximab (RTX)-treated RA.&#x0D; Results. Based on the results of several studies, predictors of response to methotrexate were high Disease Activity Score (DAS), concentration of myeloid-related proteins 8/14, high P-glycoprotein levels, low serum calprotectin and leptin levels, baseline serum concentration of tumor necrosis factor (TNF)-α, TNF receptor I, interleukin (IL)-1β, soluble CD163, numbers of CD14+highCD16, vascular cell adhesion molecule, lower expression of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p. A positive response to biological therapy was determined by male gender, younger age, lower health assessment questionnaire, erythrocyte sedimentation rate or C-reactive protein, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, tender joint count (or swollen joint count) scores, absence of comorbidities, baseline albumin, IL-34, IL-1β, D-dimer, fibrinogen, matrix metalloproteinase 3, DAS 28 and Simplified Disease Activity Index (SDAI). The plasma interferon (IFN) activity and the IFN beta/alpha ratio, IL-1Ra level were predictive in TNF antagonist-treated patients. Predictors of response to IL-6 inhibitors were anti–citrullinated protein antibody (ACPA)+, baseline Sharp/van der Heijde score, myeloid soluble intercellular adhesion molecule 1, serum levels of sIL-6R, IL-8, calprotectin, and lymphoid activation and bone remodeling markers. The prediction of the best response for rituximab was determined to be a combination of IL-33, rheumatoid factor or ACPA, IgG, and also lower number of previous biological therapies. Genetic factors, such as single-nucleotide polymorphisms at gene locus rs10919563, rs11541076, rs12083537, rs11265618, and rs1801274, and rs396991 can also be used to predict a response to treatment.&#x0D; Conclusions. One of the leading problems in the development of predictors remains the collection of high-quality and complete information from a large number of patients. For this, it is necessary to develop an digital program for collecting specific data (depending on the specific disease) and developing new algorithms for predicting the response to treatment.

Effect of Dietary Fiber on Serum Leptin Level: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Dietary fibers may induce satiety through affecting gastro-intestinal and peripheral appetite regulating hormones. Thus, we aimed to investigate the effect of dietary fiber consumption on serum leptin level compared to control diet, in short- and long- term trials, through a systematic review and meta-analysis. We searched PubMed, web of science, Scopus, ProQuest, EMBASE, and Cochrane Library to find randomized controlled clinical trials that evaluated effect of any type of dietary fiber on serum leptin level compared to control diet, until April 2019. Both short-term (1-4 days) and long-term (longer than 2 weeks) studies were selected. Mean differences (MD) of changes in serum leptin level and 95% confidence intervals were extracted from eligible studies, and random effects model was used to analyze data. Thirteen studies included the systematic review and 11 entered in the meta-analysis. No significant change was seen in serum leptin level in short-term (MD=0.02, 95% CI; -0.15, 0.20, Tau2=0.0) and long-term studies (MD=-0.10, 95% CI; -0.28, 0.08, Tau2=0.0), followed by fiber consumption. However, this effect was statistically significant in obese participants (MD=-0.36, 95% CI; -0.71, -0.02, Tau2=0.0) in long-term studies. Moreover, we found no significant results in subgroups of baseline serum leptin level, intervention duration, fiber dose, and fiber type. This meta-analysis found that taking dietary fiber for long term could lower serum leptin level, just in obese persons. However, further clinical trials are needed in this field to clarify this issue.

Low serum leptin levels are associated with malnutrition status according to malnutrition-inflammation score in patients undergoing chronic hemodialysis.

Leptin is an adipokine secreted from adipocytes that mediate lipid metabolism and inflammation. This cross-sectional study investigated the relationship between serum leptin level and nutrition status evaluated by malnutrition-inflammation score (MIS) among patients undergoing hemodialysis (HD). This study included 100 patients on HD. Nutritional status was based on MIS (malnutrition ≥7 points). Body composition, biochemistry data, and serum leptin level were evaluated. Of 100 subjects, 33 (33.0%) were categorized as having malnutrition. Compared with subjects in the well-nourished group, those in the malnutrition group had on average an older age, longer HD duration, and lower height, weight, body mass index, waist circumference, body fat mass, serum triglyceride level, and creatinine level. Serum leptin levels were also significantly lower in the malnutrition group (P < 0.001), whereas C-reactive protein (CRP) levels were higher (P = 0.002). Multivariable linear regression analysis revealed that HD duration (β = 2.06, P = 0.009), serum leptin level (β = -5.16, P < 0.001), CRP level (β = 3.33, P < 0.001), and albumin level (β = -1.95, P = 0.008) were factors independently associated with MIS. The discriminative power of serum leptin level to predict malnutrition was 0.834 (95% confidence interval: 0.747-0.901, P < 0.001). Low serum leptin level was associated with malnutrition, and serum leptin level may be a valuable marker for nutrition assessment in patients undergoing HD.

Up-Regulation of Mir-21 and Mir-130a and Serum Leptin Levels on Leg Ulcers Development in Sickle Cell Anemia

Introduction: Leg ulcers (LUs) are a cutaneous complication of sickle cell anemia (SCA), whose etiology is considered multifactorial. In the search for new candidates for modulators of SCA clinical events, recent evidence suggests the significant role of mechanisms related to post-transcriptional regulation, especially microRNAs (miRNAs). Thus, the analysis of miRNAs miR-21 and miR-130a differential expression in patients with SCA becomes an interesting approach, since both act in the regulation of several biological mechanisms related to the pathophysiology of LU, especially the tissue repair process. In addition, these miRNAs have already been related to the regulation of serum leptin levels, a strong angiogenic pleiotropic hormone that acts in the healing process of skin lesions. Therefore, the aim of the study was to investigate the influence of miR-21 and miR-130a and serum leptin levels on the development of LUs in SCA patients. Methods: After analyzing medical records, 60 SCA patients were selected. Patients who presented some of the main clinical manifestations that may have etiology due to the underlying disease (for example: osteonecrosis, stroke, priapism and acute chest syndrome) were not included. Patients with a history of LU were considered cases, and those who did not develop this complication (n=20), were considered control (median age: 26 years, range: 19-61, 50% males). The control group was called "HbSS-Control" and the case group was divided into two subgroups: Active leg ulcer group, composed of 19 patients with active LU at the time of blood collection (median age: 35 years, range: 24-56, 68% males), and healed leg ulcer group, composed of 21 patients with healed LU at the time of blood collection (median age: 34 years, range: 22-52, 43% males). In addition, it was analyzed a group of 10 donors with normal hemoglobin profile (median age: 25 years, range: 20-30, 50% males), identified as "HbAA-Control". Expression levels of miRNAs extracted from peripheral blood, using mirVanaTM PARIS Kit (Invitrogen™) were evaluated by RT-qPCR technique utilizing TaqMan® probes. Serum leptin levels of the patients were evaluated employing the ELISA method (Human Leptin ELISA Kit, Millipore®). Mann-Whitney and Kruskal-Wallis tests were applied to compare continuous variables. Results: Up-regulation of both miRNAs was observed in the active leg ulcer group in contrast to the healed leg ulcer (miR-21: P&amp;lt;0.0001, Figure 1A, Fold change [FC]=14,2; miR-130a: P=0.0004, FC=18,8, Figure 1B) and Control-HbSS groups (miR-21: P&amp;lt;0.0001, FC=34,4, Figure 1A; miR-130a: P=0.0006, FC=15,3, Figure 1B) and the HbAA-Control group (miR-21: P&amp;lt;0.0001, FC=5,8, Figure 1C; miR-130a: P=0.0009, FC=10,9, Figure 1D). However, there was no significant difference between the healed leg ulcer, HbSS-Control and HbAA-Control groups (miR-21: P=0.1829, Figure 1E; miR-130a: P=0.3537; Figure 1F). Furthermore, the active leg ulcer group had lower serum leptin levels when compared to the healed leg ulcer and Control-HbSS groups (P=0.0058; Figure 2A). The levels of leptin in the healed leg ulcer group did not differ from the Control-HbSS group (P=0.5929; Figure 2B). Conclusion: Our results demonstrated an inverse relation between the miRNAs miR-21 and miR-130a expression with serum leptin levels, suggesting that the up-regulation of these miRNAS may be related to the chronicity and healing of LUs in individuals with SCA through decreased of serum leptin levels. Disclosures No relevant conflicts of interest to declare.

Association of Body Dysmorphic Disorder with Leptin Levels in Patients with Normal Weight Undergoing Liposuction: A Matched Case Study.

Background:Liposuction is the most common aesthetic surgical procedure performed globally. Some of the patients with normal weight who seek liposuction may suffer from body dysmorphic disorder (BDD). Leptin, which is mainly produced by adipose tissue, may be associated with this condition. The aim of this study was to determine the prevalence of BDD and leptin levels in patients with normal weight seeking liposuction.Methods:Thirty-two nonobese women who sought liposuction were matched with 32 healthy volunteers by age and body mass index. Blood biochemistry, leptin levels, and BDD-Yale–Brown Obsessive-Compulsive Scale (BDD-YBOCS) questionnaires were evaluated and compared between the groups.Results:Patients who underwent liposuction had significantly higher median (interquartile range) of total BDD-YBOCS scores than healthy volunteers [25 (22–27) versus 12 (8–20); P < 0.001]. Overall, 28 (87.5%) patients had total BDD-YBOCS scores of >20, whereas 10 (31.5%) volunteers had scores of >20. Patients with total BDD-YBOCS scores of >20 had significantly lower levels of serum leptin [12.43 (7.15–16.98) ng/ml versus 15.57 (9.59–22.28) ng/ml; P = 0.043].Conclusions:Patients who underwent liposuction had a significantly higher total score of BDD-YBOCS than healthy volunteers matched by sex, age, and body mass index. Subjects with higher BDD-YBOCS scores had significantly lower serum leptin levels.

Baseline serum leptin predicts peritoneal dialysis adequacy: a single-center prospective, longitudinal study

Hyperleptinemia is often observed in peritoneal dialysis (PD) patients. But, there are few studies on the relationship between blood leptin level and PD survival, and, some of them contradict each other. The present study aimed to investigate the impact of PD initiation on the serum leptin concentrations and its association with PD adequacy. Method. A total of 23 patients with end-stage renal disease (ESRD), who started the treatment with continuous ambulatory peritoneal dialysis (CAPD), were included in this prospective single-center observational longitudinal study. Among the patients, there were 15 men and 8 women; the average age of the patient population was 52.4 ± 12.3 years. The treatment with CAPD was performed using Dianeal PD 4 with glucose concentration of 1.36% and 2.27%. The patients were screened before PD initiation and after 3- and 12- month PD treatment. Leptin levels were determined in all patients using ELISA-method. Results. The median serum leptin concentration at study entry was 10.6 [5.6-21.9] ng/mL. Leptin level and its dynamics during the year after PD treatment initiation were dependent on body mass index (BMI). The overweight or obese patients had ever-increasing leptin levels after 3- and 12- month PD treatment. Whereas in the PD patients with normal weight, we observed a significant decrease of leptin levels after 12-month PD treatment. Serum leptin concentration in the women was significantly higher compared with the men (46.4 [1.1-95] vs 9.8 [3.2-14.5] ng/mL; p = 0.02). Blood cholesterol levels had a positive correlation with serum leptin concentrations after 3- and 12- month PD treatment: r = 0.53, p = 0.01 and r = 0.56, p = 0.008, respectively. However, we did not find a statistically significant association of leptin with PD adequacy parameters after 3- and 12- month PD treatment of the patients. In the Cox proportional hazard model adjusted for gender, serum leptin level demonstrated itself as the effective factor in PD adequacy survival: HR 5.3 (95% CI 1.7; 16.3). PD adequacy survival was better in the patients with leptin concentrations above the median (≥10.6 ng/mL) compared with the patients who had serum leptin levels below the median (log rank test, χ2 = 8.2; p = 0.0042). Conclusions. Our study have demonstrated markedly elevated serum leptin level in the overweight PD patients and its strong decrease during 12 months in the patients with normal weight. Low serum leptin level before PD initiation is associated with inadequate PD.

Pre-Conditioning Serum Leptin Levels Predict Early Relapse Rates of High Risk AML after Allogeneic Stem Cell Transplantation

Background: Allogeneic stem cell transplantation (alloSCT) is an effective treatment for many hematologic diseases including intermediate- and high-risk acute myeloid leukemia (AML). Relapse of the original disease continues to be the most common cause of treatment failure following alloSCT for AML. The factors governing relapse and non-relapse mortality (NRM) following alloSCT are poorly understood. We have previously reported that weight loss prior to conditioning therapy is a risk factor for relapse of myeloid diseases following alloSCT (1). The peptide hormone Leptin is a key regulator of food intake and body weight (2). Moreover, it has known roles in regulation of metabolism and immune homeostasis (3). This retrospective study evaluates Leptin as a predictor of survival, relapse and NRM following alloSCT for hematologic malignancies.Methods: Clinical data and Leptin serum levels measured prior to start of conditioning were collected retrospectively in a cohort of patients transplanted for acute leukemias (AML and ALL, n=206). Findings from this cohort were validated in an independent validation cohort of AML patients transplanted in another institution (n=367). Distribution of serum Leptin levels was highly skewed and thus log2-transformation was applied.Results: We identified low serum Leptin as an independent predictor for early relapse following alloSCT for intermediate and advanced stage acute leukemia (AML and ALL) as defined by the EBMT score (4). Multivariate analysis of Leptin and known covariables (age at transplantation, HLA mismatch, conditioning intensity, in-vivo T cell depletion with ATG, recipient and donor sex) revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59-0.96, p=0.020) for Leptin. We observed an increased risk of NRM with higher leptin serum levels with an HR of 1.63 (1.15-2.31, p=0.006) while no statistically significant effect on OS was found. In order to visualize the effect of the continuous variable on the distribution of survival times, the quartiles of serum Leptin levels with regards to relapse, NRM and OS are shown in Figure 1. This effect on relapse was similar in intermediate and advanced stage AML patients from an independent cohort with an HR of 0.84 (0.72-0.97, p=0.020) while no statistically significant effects on NRM and OS were found. Pre-conditioning serum Leptin was confirmed as a predictor for early relapse by fitting the Cox model to the validation data.Conclusion: Low pre-conditioning serum Leptin levels appear to be an independent risk factor for early relapse following alloSCT for intermediate and advanced stage AML. Pre-conditioning serum Leptin should be explored to guide nutritional intervention in AML patients undergoing alloSCT in order to improve transplant success.ReferencesDietrich S, Radujkovic A, Stolzel F, Falk CS, Benner A, Schaich M, et al. Pretransplant metabolic distress predicts relapse of acute myeloid leukemia after allogeneic stem cell transplantation. Transplantation. 2015;99(5):1065-71.Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron. 1999;22(2):221-32.Procaccini C, La Rocca C, Carbone F, De Rosa V, Galgani M, Matarese G. Leptin as immune mediator: Interaction between neuroendocrine and immune system. Developmental and comparative immunology. 2017;66:120-9.Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T, et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009;115(20):4715-26. [Display omitted] DisclosuresBeelen:Medac: Consultancy, Other: Travel Support.