Higher Leptin Concentrations Research Articles

Gut microbiota is involved in leptin-induced thermoregulation in Mongolian gerbil (Meriones unguiculatus).

Leptin is a hormone that secreted by adipocytes and may promote energy expenditure by increasing thermogenesis. Our previous studies have shown that thermo-transient receptor potentials (thermo-TRPs) and gut microbiota are associated with thermoregulation in Mongolian gerbils, which are characterized by relative high serum leptin concentrations. Here, we test whether leptin can stimulate non-shivering thermogenesis (NST) in Mongolian gerbils, and whether thermo-TRPs and gut microbiota are involved in leptin-induced thermogenesis. First, gerbils were given acute leptin treatment (ALT) with different doses. Results showed that ALT significantly increased the body temperature of gerbils and change the composition of gut microbiota. Moreover, ALT groups showed a trend towards increased expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Then, we investigated the effect of chronic leptin treatment (CLT) on gerbils. Surprisingly, CLT did not affect gerbils' food intake and body weight, but it significantly increased the body temperature at the end. Besides, CLT did not affect the expression of thermogenic markers in BAT, white adipose tissue (WAT) and skeletal muscle. However, CLT increased the expression of leptin receptors and TRPV2 in the small intestine and affected the composition of gut microbiota. Together, our data suggest leptin may increase body temperature by regulating gut microbiota. In conclusion, the Mongolian gerbils with serum hyperleptin is beneficial for adapting the cold living environments, and TRPV2 and gut microbiota are involved.

Effect of leptin and adiponectin on the expression of cytokine genes IL-1β, IL-6 AND TNFα in lymphocytes

Metabolic syndrome (MS) is one of the world’s topical health problems. Large-scale epidemiological studies on the prevalence of MS in the world have not been conducted, but according to different authors, depending on the region of residence, the composition of the study population and the diagnostic criteria used, the incidence of MS is at least 10%, and according to estimates of the International Diabetes Federation IDF – up to 25% of the adult population. The metabolic changes in MS are explained by a disturbance in the balance of mediators synthesized by adipose tissue (adiponectin, leptin, resistin, visfatin, vaspin and others); MS is also considered as a subclinical chronic inflammatory process characterized by excessive synthesis of proinflammatory and deficiency of anti-inflammatory cytokines. According to modern ideas, changes in the cellular and humoral immunity in MS are largely due to the imbalance of adipokines: leptin and adiponectin. Increased functional activity of immune cells, including lymphocytes, leads to changes in cytokine gene expression. In the present work, we studied in vitro the expression of IL-1â, IL-6 and TNFá genes in peripheral blood lymphocytes under the influence of adipokines at concentrations characteristic of MS. As a result, differential effects of adipokines on lymphocytes of MS patients and conditionally healthy individuals were found. In conditionally healthy individuals, incubation of lymphocytes with adipokines leptin, adiponectin and their combination, as well as in the presence of physiological solution causes an increase in IL-6 gene expression. The most noticeable effect was observed when cultured with adiponectin. Thus, in norm, with a decrease in the physiological concentration of adiponectin, the expression of IL-6 in lymphocytes increases, indicating insufficient realization of the anti-inflammatory effect of adiponectin. In MS, IL-6 gene expression increases in lymphocytes isolated from peripheral blood in vitro after incubation with adiponectin, a combination of adiponectin and leptin, as well as in the presence of physiological solution. No changes in IL-6 gene expression under the effect of high concentration of leptin were detected. Probably, our results reflect the phenomenon of lymphocyte resistance to leptin action in MS, as under its influence there is not activation of lymphocytes characteristic in vivo, but on the contrary, decrease of activated subpopulations, also there is no change in IL-6 gene expression. Thus, adipokines in concentrations characteristic of metabolic syndrome influence the functional activity of peripheral blood lymphocytes.

Exogenous leptin alleviates glutamate-excitotoxic injury caused by cerebral ischemia–reperfusion in mice by affecting the expression of glutamate transporters

Ischemic stroke is characterized by high morbidity and mortality and a lack of effective therapeutic interventions. Leptin plays an important role in regulating oxidative stress, angiogenesis, hematopoiesis, etc. Although recent studies have found a neuroprotective effect of leptin, little is known about its role in cerebral ischemia. This study explores the possible roles and potential preventative mechanisms of leptin in cerebral ischemia–reperfusion injury (CIRI). An in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to replicate the CIRI model, low (0.5 mg/kg), medium (1 mg/kg) and high (2 mg/kg) concentrations of leptin were injected intraperitoneally immediately after inserting the embolic line. After 1.5 h of ischemia and 24 h of reperfusion, we examined the neural function of the mice, collected brain tissue for histological examination, and screened for the optimal concentrations of leptin intervention. On this basis, we observed the changes of cortical apoptosis injury, intracellular calcium fluorescence intensity and astrocyte glial fibrillary acidic protein (GFAP) expression and morphological changes. In addition, we also tested the expression of transporters and metabolism-related enzymes (VGLUT-1, VGLUT-2, GLAST, GLT-1, GS, ATP1α1), the expression of inflammatory factors and the content of glutamate (Glu). Compared with the I/R group, we found that leptin improved neurological deficits, reduced the area of infarcts, maintained the normal morphology of astrocytes (AST), downregulated the expression of VGLUT-1, and upregulates the expression of GLT-1 and GLAST, thereby reducing the content of Glu in the synaptic cleft. Our studies suggest that leptin may have a neuroprotective effect by decreasing the excitotoxicity of glutamate.

Deciphering the associations of selenium distribution in serum GPx-3 and selenoprotein P with cardiovascular risk factors in a healthy population with moderate levels of selenium: The ATTICA study

BackgroundSelenium (Se) is an essential micronutrient, important for human health. The relationship of Se with cardiovascular risk factors is still inconclusive, especially regarding the role of different selenoproteins. The present study evaluated the relation of total serum Se as well as its distribution in plasma selenoproteins, namely glutathione peroxidase 3 (GPx3) and selenoprotein P (SelP) with cardiovascular risk factors in a sex-specific manner, in a healthy population with moderate levels of Se. Methods: A sub-sample from the ATTICA Study’s database, consisting of 398 participants (160 females and 238 males) with data on Se and selenoproteins levels, was considered. GPx3, SelP and the main non-specific serum selenium containing protein, selenoalbumin (SeAlb) were simultaneously determined in human plasma by high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) at baseline. Results: Participants that belong to the highest tertiles of GPx3 and SelP presented the lowest blood pressure. Homocysteine was inversely associated with SelP and its ratio SelP/TSe in both sexes. In males, the lowest tertile of GPx3 showed lower adiponectin levels (0.66 ± 0.21 μg/mL) in comparison to the 2nd tertile of GPx3 (p=0.002), SelP was inversely associated with visceral adipose index (VAI) (-2.29 ± 0.81, p=0.005). Particularly, in males, the middle tertile of SelP had the lowest VAI values. Regarding females, lower Lp(a) concentration by 11.96 ± 5.84 mg/dL was observed in low SelP levels while higher leptin concentration by 2.30 ± 0.73 μg/L and lower fibrinogen concentration by 27.32 ± 13.30 mg/dL was detected in low GPx3 levels. Conclusion: Circulating selenoproteins exert differentiated effects on cardiovascular risk factors, some of them in a sex-specific manner.

The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients

IntroductionNeuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy.Materials and methodsIn 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin (LEP) and neuropeptide Y (NPY) by real-time PCR.ResultsLeptin concentration was significantly higher in obese patients than in patients with normal or low weight (p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy (p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8–16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001–0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243–1.0715, p = 0.0953).ConclusionAssessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.

Features of the course of irritable bowel syndrome in overweight and obese people

The aim of the study: to study the characteristics of the course of irritable bowel syndrome (IBS), associated with overweight and obesity, to optimize the management of this group of patients. Material and methods. An open-label cross-sectional study was performed including 175 participants aged 18 to 44 years (mean age 30.06 ± 6.15 years). Group 1 included 100 patients with IBS aged 18 to 44 years (mean age 30.63 ± 6.37 years, BMI 25.88 ± 6.28 kg/m2). In group 1, subgroup 1A included 50 people with IBS associated with overweight or obesity. Subgroup 1B included 50 IBS patients with normal weight. Group 2 included 75 people who did not suffer from IBS, aged from 19 to 43 years (mean age 29.31 ± 5.81 years, BMI 27.80 ± 6.20 kg/m2). Subgroup 2A included 50 participants who did not suffer from IBS and were overweight or obese. Subgroup 2B included 25 apparently healthy participants. The presence and severity of IBS symptoms were assessed using a 10-point scale. The severity of gastrointestinal symptoms, the presence of anxiety and depression, the level of specific anxiety, quality of life and eating habits were assessed using verified questionnaires. All participants underwent a study of the levels of leptin and adiponectin in the blood serum and zonulin in the feces. Results. The characteristic clinical stigmas in patients suffering from IBS associated with overweight and obesity are described: IBS with a predominance of constipation, severe course of the disease, high incidence of signs of depressive and anxiety disorders, special eating habits characterized by the predominance of flour, sweet, fatty and salty foods in the diet food, severe disturbances in the permeability of the intestinal epithelial barrier. High concentrations of leptin and low levels of adiponectin in the blood serum of such patients may play a significant role in the formation of IBS symptoms. Conclusion. The results obtained open up opportunities for research into the pathogenetic mechanisms of the formation of IBS in people with overweight and obesity, as well as modification of existing treatment regimens for patients with IBS.

Relationship of bisphenol A substitutes bisphenol F and bisphenol S with adiponectin/leptin ratio among children from the environment and development of children cohort

BackgroundBisphenol A (BPA) is known as an obesogenic endocrine disruptor. Bisphenol S (BPS) and F (BPF) are substitutes that have recently replaced BPA. ObjectivesTo investigate the relationships of urinary bisphenols (BPA, BPS and BPF) with adiposity measurements (obesity, BMI z-score, and fat mass), serum adipokine levels (adiponectin and leptin), and adiponectin/leptin ratio (A/L ratio) in 6- and 8-year-old children. MethodsA total of 561 children who participated in the Environment and Development of Children cohort (482 and 516 children visited at age 6 and 8, respectively) at Seoul National University Children’s Hospital during 2015–2019 were included. Urinary BPA levels were log-transformed. BPS levels were categorized into three groups (non-detected, lower-half, and higher-half of detected), and BPF levels were classified into two groups (non-detected and detected). ResultsThe urinary BPS higher-half group had a higher BMI z-score (β = 0.160, P= 0.044), higher fat mass (β = 0.104, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (β = 0.074, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The BPA levels showed no consistent associations with outcomes, except for isolated associations of BPA at age 6 with a higher BMI z-score at age 6 (P= 0.016) and leptin at age 8 (P= 0.021). ConclusionsIncreased exposure to BPS and BPF is associated with higher fat mass and leptin concentration, lower serum adiponectin, and lower A/L ratio in children. These findings suggest potential adverse effects of BPA substitutes on adiposity and adipokines. No consistent association of BPA exposure with outcomes could be partly explained by the decreasing BPA levels over time.

Evaluation of the production of oppositional cytokines IL-6 and IL-10 in the culture of mononuclear blood leukocytes in rats with metabolic syndrome

Aim: to evaluate the secretory activity of mononuclear blood leukocytes by the level of in vitro production of oppositional cytokines (pro-inflammatory IL-6 and anti-inflammatory IL-10) in rats in a model of diet-induced metabolic syndrome (MS) against the background of changes in the concentration of adipokines leptin and adiponectin.&#x0D; Materials and methods. In male Wistar rats, MS was modeled by keeping for 12 weeks on a high-fat and high-carbohydrate diet; control group animals received a normal diet. Mononuclear leukocytes isolated by gradient centrifugation from heparinized blood were cultured in a medium based on RPMI-1640 (concentration of 2×106 cells in 1 ml of medium) for 24 hours in sterile tubes in a CO2-incubator in two variants – without the addition of an inducer and with the addition of bacterial lipopolysaccharide (LPS). The concentration of cytokines in the culture fluid, hormones leptin and adiponectin in the blood serum was determined by enzyme immunoassay. Statistical data processing was carried out in the SPSS Statistics 23.&#x0D; Results. In animals exposed to a 12-week high-fat and high-carbohydrate diet, against the background of an increase in body weight, the specific mass of visceral adipose tissue, metabolic disorders (hyperglycemia, impaired glucose tolerance, dyslipidemia), high concentrations of leptin and low concentrations of adiponectin, the ability of mononuclear blood leukocytes to produce IL-6 and IL-10 in vitro at the basal level and when stimulated by bacterial LPS does not change.&#x0D; Conclusion. Probably, the morphofunctional status and secretory profile of monocyte-macrophage system cells depends on the severity and duration of the metabolic and hormonal imbalance associated with obesity and systemic chronic inflammation.

The effect of heat stress on performance, fertility, and adipokines involved in regulating systemic immune response during lipolysis of early lactating dairy cows

The aim of this study was to assess the potential effect of heat stress on dairy cow productivity, fertility, and biochemical blood indices during the early lactation stage in a temperate climate. Additionally, the study aimed to determine the role of leptin and adiponectin in regulating the immune response accompanying lipolysis after calving in dairy cows. The study included 100 clinically healthy Polish Holstein-Friesian dairy cows selected based on parity and 305 d of milk yield from 5 commercial farms with similar herd management and housing systems. Prospective cohort data were recorded from calving day until 150 d in milk, and microclimate loggers installed inside the barns were used to record temperature and relative humidity data to calculate daily temperature-humidity index (THI) on the calving day, through +7, +14, and +21 d during early lactation. Additionally, monthly productive performance parameters such as milk yield, chemical composition, fatty acids composition, and fertility indices were analyzed. Results showed that the THI from calving day through +7, +14, and +21 d during early lactation was negatively associated with fertility parameters such as delayed first estrus postpartum and an elongated calving interval, respectively, by 29, 27, 25, and 16 d. Furthermore, an increase in THI value during early lactation was associated with an elongated artificially inseminated service period, days open, and intercalving period. Increasing THI from calving day (0 d) through +7, +14, and up to +21 d during early lactation was also linked to decreased milk yield by 3.20, 4.10, 5.60, and 5.60 kg, respectively. The study also found that heat stress during early lactation was associated with a lower body condition score in dairy cows and higher concentrations of leptin, nonesterified fatty acids, and β-hydroxybutyrate, accompanied by a drastic reduction in adipose tissue-secreted adiponectin levels after calving. Additionally, heat stress-induced lipolysis in adipose tissue caused an inflammatory response that increased biochemical blood indices associated with immune responses such as cytokines, acute phase proteins, and heat shock protein. These findings suggest that exposing dairy cows to heat stress during early lactation can negatively affect their productive performance, fertility, and biochemical blood indices in subsequent lactations. Thus, farm management changes should be implemented during early lactation to mitigate the negative consequences of heat stress occurrence.

Leptin Modulates the Differentiation of Keratinocytes via Autophagy in Psoriasis Patients With Metabolic Syndrome

Objective: Psoriasis is associated with a high prevalence of metabolic syndrome (MS), and patients with concomitant psoriasis and MS are more severely affected and less responsive to treatment. However, the molecular mechanisms behind these effects are unknown. Recent studies have shown that leptin may serve as a molecular link between psoriasis and MS, suggesting that high leptin concentrations may exacerbate psoriasis. However, the molecular mechanism of this effect is still unclear. We aimed to investigate the effect of leptin on autophagy in patients with psoriasis. Methods: From January 2021 to June 2022 in PLA General Hospital, we enrolled 51 patients with psoriasis, including 21 patients with MS and 30 without MS, and 30 healthy controls who had undergone nevus surgery. We measured the epidermal leptin, P62, and LC3B concentratins of patients by immunohistochemistry, and measured the serum leptin concentration by enzyme-linked immunosorbent assay. We then performed correlation analyses to compare these proteins’ concentrations between patients with concomitant psoriasis and MS, patients with psoriasis alone, and healthy control groups. Additionally, we performed western blotting after in vitro culture of HaCaT cells with different concentrations of leptin and measured the expression levels of the autophagy markers Beclin1, LC3B, and P62; the differentiation markers K10, K16, and K17; and PI3K/AKT/mTOR signaling pathway-related proteins of HaCat cells. Next, we transfected ATG5 into HaCaT cells to revert autophagy and used the specific PI3K inhibitor LY294002 to block PI3K/AKT/mTOR signaling. The expression levels of K10, K16, and K17 of HaCat cells were again measured. One-way analysis of variance was used for the comparison of means of multiple samples, and LSD-t post hoc test was used for comparison between the 2 groups. The counting data were analyzed by the chi-square test. Correlations were evaluated by Pearson correlation analysis. Results: The serum leptin concentration was significantly higher in patients with concomitant psoriasis and MS than in patients with psoriasis alone, and healthy controls (1,330.0 ± 244.2 pg/mL, 1,041.0 ± 282.7 pg/mL, and 760.4 ± 361.1 pg/mL, P &lt; 0.001). Optical density of epidermal leptin concentration was significantly higher in patients with psoriasis and MS than in patients with psoriasis alone and healthy controls (0.59 ± 0.15, 0.39 ± 0.12, and 0.27 ± 0.19, P &lt; 0.001). The level of the autophagy marker LC3B was strongly reduced and that of P62 was strongly increased in the epidermis of patients with concomitant psoriasis and MS compared with patients with psoriasis alone and healthy controls (optical density value: LC3B: 0.27 ± 0.11, 0.29 ± 0.13, and 0.46 ± 0.17, P &lt; 0.001; P62: 0.18 ± 0.08, 0.13 ± 0.03, and 0.10 ± 0.03, P &lt; 0.001). We also observed a positive correlation between leptin and P62 concentrations in the blood (r = 0.40, P &lt; 0.001) and epidermis (r = 0.27, P = 0.017), and a negative correlation between serum leptin concentrations and epidermal LC3B concentrations (r = −0.39, P &lt; 0.001). In vitro, leptin significantly decreased Beclin1 and LC3B and increased P62. Western blotting showed that leptin treatment resulted in decreased expression of K10, and increased expressions of K16 and K17; when the decrease in autophagy was restored by ATG5, this phenomenon was reversed. In addition, leptin treatment significantly upregulated the expressions of phosphorylated PI3K, AKT, and mTOR in HaCaT cells compared with the control treatment; when the expression of phosphorylated PI3K was significantly inhibited by LY294002, leptin did not reverse the decreased expression of these proteins. Conclusion: Leptin is negatively associated with autophagy in psoriasis, and leptin markedly decreased autophagy and affected keratinocyte differentiation by downregulating autophagy via the PI3K/AKT/mTOR pathway. Our study enhances the understanding of leptin as the link between MS and psoriasis and provides potential therapeutic targets for patients with concomitant psoriasis and MS.

Elevated plasma leptin levels are associated with vascular access dysfunction in patients on maintenance hemodialysis.

Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.

Does human milk composition predict later risk of obesity? A systematic review

BackgroundPossible mechanisms behind the association of breastfeeding with a lower risk of later obesity are unknown but one possibility is the unique composition of human milk. Here, we systematically reviewed the evidence linking breast-milk macronutrient and hormonal composition with later obesity.MethodsWe searched 7 databases for studies that included infants predominantly breast-fed for the first 3 months and which analysed associations between a measure of breast-milk composition and later (> 6 months) measures of obesity or body composition.Results47 publications were identified for full-text screening, of which 10 were eligible and only 3 found significant associations. Higher leptin concentration in breast milk at age 1 month was associated with lower infant BMI at 12, 18 and 24 months of age (1 study). Higher breast-milk adiponectin concentration at 6 weeks and 4 months were associated with adiposity at age 12 and 24 months (1 study). In 1 study, breast-milk carbohydrate content was positively associated, and fat content negatively associated, with adiposity at age 12 months. No significant associations were found between other hormones or macronutrients in human milk and later risk of obesity or body composition.ConclusionsThe evidence linking breast-milk composition with later obesity was inconsistent and confined to single, individual studies. Our review highlights the methodological limitations of previous studies and the need for further research in this area.

Ассоциации лептина и адипонектина у больных синдромом раздраженного кишечника с избыточной массой тела и ожирением

Irritable bowel syndrome (IBS) in overweight and obese individuals is characterized by a more severe course than in patients with normal weight. The purpose. To assess the level of adipokines (leptin and adiponectin) in blood serum, the correlation of these laboratory markers with the clinical manifestations of IBS, quality of life, eating habits, and signs of anxiety and depression based on the results of using a special questionnaire in patients with IBS. Material and methods. An open cohort cross-sectional study was conducted with the inclusion of 175 participants aged 18 to 44 years (mean age 30.06 ± 6.15 years). Group 1 included 100 obese or overweight IBS patients aged 18 to 44 years (mean age 30.63 ± 6.37 years, BMI 25.88 ± 6.28 kg/m2). In group 1, subgroup 1A included 50 people with IBS associated with overweight or obesity. In subgroup 1B – 50 people suffering from IBS, with normal weight. Group 2 included 75 people without IBS, aged 19 to 43 years (mean age 29.31 ± 5.81 years, BMI 27.80 ± 6.20 kg/m2). Subgroup 2A included 50 non-IBS participants who were overweight or obese. Subgroup 2B included 25 apparently healthy participants. IBS symptoms were assessed using a 10-point scale. Using verified questionnaires, the severity of gastrointestinal symptoms, the presence of anxiety and depression, the level of specific anxiety, quality of life and eating habits were assessed. Results. IBS patients with overweight and obesity are characterized by higher levels of leptin and low levels of adiponectin than patients with normal weight (Mann – Whitney test, p &lt; 0.05). Adipokine levels correlate with high cravings for sweet, fatty, starchy, and salty foods. A higher concentration of leptin is characteristic of patients suffering from IBS with a predominance of constipation (Mann – Whitney test, p &lt; 0.05). High levels of leptin and low levels of adiponectin in overweight and obese IBS patients correlate with more severe symptoms of abdominal pain, flatulence, poor quality of life, and more frequent signs of anxiety and depression (Spirmen test p &lt; 0.05, Mann – Whitney test, p &lt; 0.05). Conclusion. The results obtained suggest a significant role of adipokines in the formation of more severe symptoms in IBS patients with overweight and obesity compared to patients with normal weight

Concentration-dependent effects of leptin on osteoarthritis-associated changes in phenotype of human chondrocytes

ABSTRACT Metabolic syndrome is a risk factor for osteoarthritis. Elevated leptin levels have been implicated as a potential cause of this association. Previous studies have shown that supra-physiological leptin concentrations can induce osteoarthritis-like changes in chondrocyte phenotype. Here, we tested the effects of leptin in the concentration range found in synovial fluid on chondrocyte phenotype. Chondrocytes isolated from macroscopically normal regions of cartilage within osteoarthritic joints from patients undergoing knee arthroplasty, all with body mass index >30 kg/m2 were treated with 2-40 ng/ml leptin for 24 h. Chondrocyte phenotype marker expression was measured by RT-qPCR and western blot. The role of HES1 in mediating the effects of leptin was determined by gene knockdown using RNAi and over-expression using adenoviral-mediated gene delivery. Treatment of chondrocytes with 20 or 40 ng/ml leptin resulted in decreased SOX9 levels and decreased levels of the SOX9-target genes COL2A1 and ACAN. Levels of HES1 were lower and ADAMTS5 higher in chondrocytes treated with 20 or 40 ng/ml leptin. HES1 knockdown resulted in increased ADAMTS5 expression whereas over-expression of HES1 prevented the leptin-induced increase in ADAMTS5. An increase in MMP13 expression was only evident in chondrocytes treated with 40 ng/ml leptin and was not mediated by HES1 activity. High concentrations of leptin can cause changes in chondrocyte phenotype consistent with those seen in osteoarthritis. Synovial fluid leptin concentrations of this level are typically observed in patients with metabolic syndrome and/or women, suggesting elevated leptin levels may form part of the multifactorial network that leads to osteoarthritis development in these patients.

Systemic Circulating Leptin – Aiding New Dimension of Immune-Related Skin Carcinogenesis and Lipid Metabolism

AIM: The link between the development of melanoma skin cancer and obesity is gaining recently an increased attention. A plethora of immune-related factors sustain a chronic inflammatory state modulated by the metabolic imbalance, the main examples being tumor necrosis factor alpha, interleukin 6, monocyte chemoattractant protein (MCP1), and several adipokines. Among the adipokines leptin (LEP) is steadily increasing interests as it involved in modulating different signaling pathways (e.g., JAK2/STAT3 and MAPK cascade/FOS) and immune cells fate by promoting the switch of memory cells to T helper-1 cell response, increases CD4+CD25- T-cell proliferation, and reduces autophagy during T-cell receptor stimulation. Our work investigates in a pilot study, using protein microarray technology, the LEP circulatory levels in melanoma patients in comparison to other cytokines and chemokines already reported as significantly involved in melanoma initiation and progression. METHODS: Serum from melanoma cases and pool of serum from healthy volunteers were analyzed by an antibody array platform for a 42-cytokine profile. RESULTS: The investigation of cytokines, chemokines, and growth factors has shown that all the proinflammatory circulating molecules are elevated in the melanoma patient’s serum. Inflammatory cytokines were found elevated and were correlated to the more advanced stage of the investigated patient (M2). The highest circulatory level was registered for LEP in both melanoma cases; moreover, in M1 patient, although the LEP level was completely comparable with the one found in M2, its IL-1 serum level was normal. In addition, there are ten analytes that show clear abnormal values and in patient M2 high LEP concentration is correlated with high IL-1, MCP-2, MCP-3, MCSF, and TARC serum concentrations. CONCLUSION: Leptin is pleiotropic adipocytokine involved in various diseases, including skin cancer and melanoma. As it is involved in favoring inflammation and further tumorigenesis, the development of effective leptin-based therapeutic approaches opens new possibilities of adjuvant therapy in skin cancers.

Maternal obesity is associated with a higher number of regulatory-T-cells in newborns without affecting suppression.

Maternal obesity (MO) is associated with a higher risk of immune-mediated diseases in the offspring and higher leptin levels in cord blood (CB). This study evaluates the number and function of lymphocyte subtypes in CB related to MO and its relationship with leptin concentration and leptin receptor expression. Pregnant women with (n = 32) or without obesity (n = 41) were enrolled at delivery. Cord blood mononuclear cells were separated with Ficoll-Hypaque. B and CD4+, regulatory and effector Tcells were quantified by Flow Cytometry. Cord blood leptin concentration was measured by ELISA, and the leptin receptor (sLepR) on Treg cells was determined by Flow Cytometry. MO was associated with higher numbers of CD4+, Treg and effector Tcells in the CB of their offspring, without differences in the suppressive function of Tregs. Female offspring had a higher number of these cells and a higher cord leptin concentration. Tregs expressed higher levels of sLepR than effector Tcells, without differences between groups. MO is associated with changes in the newborn's immune profile, more evident in female newborns with higher leptin concentrations. More studies are needed to identify the mechanisms by which the high levels of cord leptin in the newborn of women with obesity could affect the offspring's immune system.

High estradiol levels during a long agonist IVF protocol are associated with decreased food intake, higher leptin concentrations, and lower levels of high-sensitivity C-reactive protein

PurposeTo study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol.MethodsFifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test.ResultsDuring the stimulation protocol, leptin concentrations elevated (P < 0.001), and energy intake decreased (P = 0.03), while estradiol levels increased (P < 0.001). GLP-1 levels unchanged (P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased.ConclusionNo increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.

Blood hormone concentrations as markers and predictors of porcine meat production and quality?

Context The applicability of hormones in the prediction of meat production in non-ruminant species has been poorly examined. Aims To examine the applicability of plasma concentrations of leptin, estradiol, progesterone and insulin-like growth-factor I (IGF-I) for characterisation and early prediction of the production and quality of meat in gilts. Methods Animals were compared at 150 days of age with below (‘low’) and above (‘high’) median hormone concentrations and their traits of meat production and quality at the age of 200 days. Key results Animals with a high leptin concentration in blood at the age of 150 days had higher slaughter and carcass weights and weight of ham, but a lower lean meat content at the age of 200 days, than did the gilts with a low leptin concentration. Animals with a high estradiol concentration had a higher carcass weight, weight of ham and backfat thickness and a lower electrical conductivity of musculus semimembranosus than did animals with a low estradiol concentration. High blood IGF-I concentration was associated with a higher slaughter weight, carcass weight and lean meat content. No significant differences between the animals with ‘high’ and ‘low’ progesterone concentration and meat characteristics have been found. Conclusions These observations confirm the involvement of leptin, IGF-I and estradiol in up-regulation of meat production in pigs. Furthermore, they suggest that leptin can be useful for characterisation and prediction of fat production, whereas IGF-I and estradiol (but not progesterone) could be both markers and predictors of porcine growth and meat production. Implications The blood concentrations of these hormones could help in characterisation and selection of pigs for meat production.

Hormonal indexes as predictors of porcine reproductive traits.

The aim of the present study was to examine the applicability of several hormonal indexes for early prediction of puberty and reproductive state in pigs. For this purpose, we have compared the level of hormones leptin, estradiol, progesterone, and IGF-I in the blood of gilts at 150 days of age and their indexes of puberty and ovarian state at the age of 200 days. The association between blood leptin, estradiol, progesterone, and IGF-I and indexes of future reproductive state has been demonstrated. High blood concentrations of leptin and IGF-I levels were associated with relatively low reproductive traits, while high levels of estradiol and progesterone were associated with future high reproductive indexes. These observations are the first demonstration of the applicability of these endocrine indexes for prediction of porcine reproductive traits.

High Post-Treatment Leptin Concentration as a Prognostic Biomarker of the High Risk of Luminal Breast Cancer Relapse: A Six-Year Comprehensive Study.

(1) Background: Nowadays, obesity is well-recognised as a significant risk factor for many chronic diseases, for example, hypertension, diabetes, atherosclerosis and cancer. This study is designed to investigate the prognostic value of the pre- and post-treatment serum levels of adiponectin and leptin in luminal A and B invasive breast cancer (IBrC) patients based on six-years follow-up. (2) Methods: Among 70 patients who underwent breast surgery, 35 were Stage I and 35 were Stage II. The concentrations of pre- and post-treatment adiponectin and leptin were evaluated with a specific ELISA kit. The median follow-up was 68.5 months (inter-quartile range (IQR) = 59-72 months) with a recurrence rate of 15.71%. (3) Results: Generally, concentrations of leptin and adiponectin increased after adjuvant therapy. Follow-up showed a significantly higher incidence of disease relapse in IBrC patients with a high post-treatment concentration of leptin (25.71% vs. 5.71% of cases with a low post-treatment concentration of leptin). A post-treatment leptin concentration of 26.88 ng/mL with a specificity of 64.9% and a sensitivity of 88.9% was determined as the best cut-off value to distinguish patients with disease recurrence from those without disease relapse. (4) Conclusions: Our results demonstrated that only the post-treatment serum leptin concentration may be of value as a prognostic indicator and could contribute to predicting a future outcome for patients with early-stage IBrC.