Lower Leptin Concentrations Research Articles

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.

SAT089 Natural History Of Generalized Lipodystrophy Following Early Vs. Late Metreleptin Treatment

Abstract Disclosure: M. Brush: None. M. Lightbourne: None. S. Auh: None. R.J. Brown: None. Generalized lipodystrophy (GLD) is characterized by near total loss of subcutaneous fat resulting in low leptin concentrations. Patients with GLD exhibit metabolic abnormalities such as severe insulin resistance, diabetes mellitus, hypertriglyceridemia, proteinuria, and non-alcoholic fatty liver disease (NAFLD), that are progressive over time. Leptin replacement therapy using metreleptin is effective in improving these metabolic abnormalities. It is unknown if starting metreleptin therapy early versus late in the clinical course will change the natural history of this disease. We hypothesize that starting metreleptin early versus late will lead to better long-term control of diabetes, hypertriglyceridemia, and proteinuric nephropathy. This is a single-center retrospective analysis of subjects with congenital and acquired generalized lipodystrophy (n=67). Fasting serum insulin, glucose, lipids, HbA1c (A1c), and 24 hr urine protein excretion, and insulin and c-peptide areas under the cover (AUC) from oral glucose tolerance tests were assessed at baseline, after 6 months of metreleptin, and at 12 month intervals thereafter. For each outcome parameter, subjects were divided into early and late treatment groups. For A1c, early treatment was defined as <7%. For all other parameters, early treatment was defined as being < the upper limit of normal for that parameter. The effect of early vs late treatment for each parameter was analyzed using linear mixed models adjusted for age and genetics, and excluding baseline metabolic parameters. Follow-up diabetes control was better with early metreleptin treatment as assessed by both glucose and A1c. Fasting glucose was 47 mg/dl lower during follow-up with early (<100 mg/dL) vs. late (≥ 100 mg/dL) treatment (p=0.0038) and A1c was 1.37% lower with early (<7%) vs late (≥7%) treatment (p=0.0015). At baseline, the early group defined by A1c had higher insulin secretion based on 48.3% higher c-peptide AUC (p=0.0185) and 161% higher insulin AUC (p=0.0029). At follow-up, the early group maintained a 37.8% higher c-peptide (p<0.0001) and 80.4% higher insulin AUC (p<0.0001). Urine protein excretion was 366 mg/24hr lower during follow-up in the early group (<300 mg/24hr) compared to the late group (≥300 mg/24hr) (P=0.0031). Triglycerides were 96 mg/dL lower during follow-up between the early (<150 mg/dL) vs late (≥150) groups (p=0.0116). In conclusion, patients with generalized lipodystrophy treated with metreleptin prior to the onset of clinically significant metabolic disease showed better age-adjusted metabolic control over time for diabetes, hypertriglyceridemia, and proteinuria. Lower insulin and C-peptide secretion in the late treatment group suggest that worse diabetes control after metreleptin in this group may be attributable to irreversible loss of beta cell function prior to metreleptin. Presentation: Saturday, June 17, 2023

Restrição de Crescimento Intrauterino e os fatores de risco associados no Brasil

Introduction: Intrauterine Growth Restriction is defined as the inability of the fetus to reach its growth potential and can be caused by maternal, placental and fetal factors. Objective: The study aims to make a major social contribution, in order to help the health sectors develop actions aimed at improving the quality of life of pregnant women, promoting changes in behaviors that are harmful to the fetus and thus contributing to reducing infant morbidity and mortality. Methodology: A bibliographic survey was carried out in the Scielo, PubMed and VHL databases, between 2010-2020, with the descriptors and their combinations in Portuguese and English, using the Boolean operators: "fetal growth retardation" OR "intrauterine growth retardation" OR "intrauterine growth restriction" AND "risk factors" AND "intrauterine growth restriction" AND "Brazil". After applying inclusion and exclusion criteria, 10 articles were selected. Results: Analysis of the articles showed that Intrauterine Growth Restriction is strictly related to five themes: evolution in prenatal treatment; socioeconomic factor; low birth weight; fetal mortality and serum leptin concentration, eclampsia and HIV. Conclusion: The analyses available on the main categories related to IUGR showed that lack of prenatal care, poor socioeconomic situation, low leptin concentration during pregnancy, pre-eclampsia and viral infections such as HIV are risk factors for IUGR in Brazil.

Intermittent vs. continuous swimming training on adipokines and pro-inflammatory cytokines in metabolic syndrome experimental model.

In this study, metabolic syndrome-affected ratswere studied to examine how intermittent and continuous swimming training influenced adipokines and pro-inflammatory cytokines. Forty-eight male Wistar rats were randomized inthis experimental study into four groups (n=8), including normal control (NC), metabolic syndrome (MS), continuous swimming training with metabolic syndrome (CT-MS: load 0-3% body mass, 5d/wk, for 8weeks), and intermittent swimming training with metabolic syndrome (IT-MS: load 5-16% body mass, 5d/wk, for 8weeks). The serum levels of metrnl, adipolin, irisin, leptin, TNF-α, and IL-6 were measured using the ELISA test. The IT-MS and NC groups exhibited significantly lower leptin concentrations than the CT-MS group (p=0.001). The irisin, meteorin, and adipolin serum levels increased significantly in CT-MS and IT relative to the NC and CT-MS groups (p=0.001), with the changes being more pronounced in the IT group (p=0.05). TNF-α and IL-6 were inclined in the CT-MS group compared with the other three groups (p=0.001), while IL-6 was increased in the IT group (p=0.024). Intermittent swimming is more effective thancontinuous swimming training in improving adipokines in rats with metabolic syndrome.

Breast milk leptin concentrations and infant anthropometric indicators in SGA versus non-SGA breastfed infants born at term

Leptin concentrations in breast milk can influence metabolic programming during the first months of life. Small for gestational age (SGA) newborns show a peculiar growth pattern after birth, which can lead to adulthood diseases. This study aims to assess an association between leptin concentration in mature breast milk and the infant anthropometric indicators of the SGA and the non-SGA groups, in addition, to comparing the hormone level between these groups. A longitudinal study was performed with mother-infant pairs. The maternal sociodemographic information was collected in the first 48 h postpartum. Breast milk was collected at one month postpartum and leptin concentrations were obtained by immunoassays. The infant anthropometric measurements were collected at three and six months postpartum and included weight, height (to body mass index-BMI calculated), triceps skinfold (TSF), and subscapular skinfold (SSF). The BMI for age (BMI/A), TSF, and SSF were calculated by Z-score indicators. Data from 67 mother-infant pairs (n = 16 SGA and n = 51 non-SGA) were analyzed. In univariate analyses, the breast milk of the SGA group had lower leptin concentrations than the non-SGA group (p = 0.006), however, after adjustment, there was no difference between groups (p = 0.181). In the SGA group, there was a significant association between leptin concentrations and lower SSF at six months in infants, after adjustment (p = 0.003). In the non-SGA group, the breast milk leptin was associated with lower BMI/A at three and six months in infants, after adjustment (p = 0.002 and p = 0.010, respectively). The association between breast milk leptin concentrations with SSF in the SGA group and BMI/A in the non-SGA group suggests that leptin may be a modulating factor in infant growth in the first months of life.

Adolescent menstrual dysfunction as a marker of future disorders of women’s sexual and reproductive health

The literature review considers the health state in women of early reproductive age. This is related to the common factors of formation that arise in adolescence, and are clinically manifested in the reproductive age. Disorders of the reproductive system functioning in puberty often lead to infertility, obstetric complications and perinatal losses. Ghrelin is a factor in the pathogenesis of functional amenorrhea during weight loss. Its concentration has a negative correlation with body mass index and androgen levels in the female body. Excessive physical exertion is one of the causes of functional amenorrhea, because this pathology is associated with increased levels of β-endorphin and ghrelin, as well as extremely low concentrations of leptin. Recent researches have demonstrated the importance of hidden genetic reproductive polymorphisms in women with the above-mentioned risk factors for amenorrhea for the future impairment of fertility. That is why women without genetic polymorphisms are able to restore both menstrual and reproductive functions after eliminating the influence of risk factors. However, in patients with some types of genetic mutations, amenorrhea persists despite the normalization of body weight, disappearance of stress and/or reduction of physical exertion. Under conditions of war in Ukraine, there is an increase in the frequency of hypothalamic dysfunctions in women of active reproductive age with a decrease in body weight against the background of stress, head injuries, which gives the problem an extreme acuteness and urgency. An example of a clinical manifestation of functional gonadotropin insufficiency is a menstrual disorder with the formation of secondary amenorrhea in 35 % of cases. Stress-induced (psychogenic) amenorrhea is one of the most common causes of functional gonadotropin deficiency. Menstrual and sexual female dysfunction is a multifactorial disorder that impairs women’s fertility, leads to pregnancy loss, infertility, and abnormal gestation. Due to dysmetabolic disorders, violations of ovarian steroidogenesis with hypothalamic-pituitary imbalance, this problem becomes multidisciplinary.

РОЛЬ ЛЕПТИНА ПРИ РАЗЛИЧНОЙ ВОЗРАСТ-АССОЦИИРОВАННОЙ ПАТОЛОГИИ В СТАРЧЕСКОМ ВОЗРАСТЕ И У ДОЛГОЖИТЕЛЕЙ

Introduction. Leptin is an adipokine synthesized by adipose tissue. This substance is involved in the development of some age-related pathological conditions. Aim. Determination of leptin concentration and analysis of the relationship of this adipokine with obesity and other pathological conditions in elderly patients and centenarians. Material and methods. This work was a cross-sectional study. 110 very elderly patients and centenarians were enrolled in the study: 90 with coronary artery disease – in the study group, 20 without coronary artery disease– in the control group. The mean age of study patient was 88.5+4.5 years. The serum leptin concentration was determined by enzyme-linked immunosorbent assay. Normal leptin values for women were 2.6-11.1 ng/ml, for men – 2.0-5.6 ng/ml. Results and discussion. Elevated leptin levels were found in 58.2% of patients, decreased – in 16.4%, normal – in 25.4%. In patients with coronary artery disease the mean concentration of leptin reached 16.7 ng/ml, in patients without coronary artery disease– 15.3 ng/ml (p=0.6). In patients with chronic heart failure the probability of detecting low leptin levels increased by 3.2 times, compared with patients without heart failure (OR=3.2; 95% CI=1.1-9.9; p=0.03). In patients with obesity the mean leptin level was 28.5 ng/ml, while in patients without obesity – 12.2 ng/ml (p=0.00002). The significant correlation was found between the leptin concentration and body mass index (p<0.000001), as well as fat mass (p=0.000001). Higher leptin levels were observed in patients with diabetes mellitus (26.3 ng/ml vs 13.5 ng/ml in patients without diabetes mellitus, p=0.0003). In patients with low leptin concentration lower bone mineral density was registered (p=0.0003). Conclusion. The study results suggest frequent leptin pathology in very elderly patients and centenarians, both with and without coronary artery disease. Higher leptin levels are associated with various metabolic disorders. Lower leptin levels are typical for patients with chronic heart failure.

C-reactive protein partially mediates the inverse association between coffee consumption and risk of type 2 diabetes: The UK Biobank and the Rotterdam study cohorts

Coffee is among the most consumed beverages worldwide. Coffee consumption has been associated with lower risk of type 2 diabetes mellitus (T2D), but underlying mechanisms are not well understood. We aimed to study the role of classic and novel-T2D biomarkers with anti- or pro-inflammatory activity in the association between habitual coffee intake and T2D risk. Furthermore, we studied differences by coffee types and smoking status in this association. Using two large population-based cohorts, the UK-Biobank (UKB; n=145,368) and the Rotterdam Study (RS; n=7111), we investigated associations of habitual coffee consumption with incident T2D and repeated measures of insulin resistance (HOMA-IR), using Cox proportional hazards and mixed effect models, respectively. Additionally, we studied associations between coffee and subclinical inflammation biomarkers including C-reactive protein (CRP) and IL-13, and adipokines, such as adiponectin and leptin, using linear regression models. Next, we performed formal causal mediation analyses to investigate the role of coffee-associated biomarkers in the association of coffee with T2D. Finally, we evaluated effect modification by coffee type and smoking. All models were adjusted for sociodemographic, lifestyle and health-related factors. During a median follow-up of 13.9 (RS) and 7.4 (UKB) years, 843 and 2290 incident T2D cases occurred, respectively. A 1 cup/day increase in coffee consumption was associated with 4% lower T2D risk (RS, HR=0.96 [95%CI 0.92; 0.99], p=0.045; UKB, HR=0.96 [0.94; 0.98], p<0.001), with lower HOMA-IR (RS, log-transformed β=-0.017 [-0.024;-0.010], p<0.001), and with lower CRP (RS, log-transformed β=-0.014 [-0.022;-0.005], p=0.002; UKB, β=-0.011 [-0.012;-0.009], p<0.001). We also observed associations of higher coffee consumption with higher serum adiponectin and IL-13 concentrations, and with lower leptin concentrations. Coffee-related CRP levels partially mediated the inverse association of coffee intake with T2D incidence (average mediation effect RS β=0.105 (0.014; 0.240), p=0.016; UKB β=6.484 (4.265; 9.339), p<0.001), with a proportion mediated by CRP from 3.7% [-0.012%; 24.4%] (RS) to 9.8% [5,7%; 25.8%] (UKB). No mediation effect was observed for the other biomarkers. Coffee-T2D and coffee-CRP associations were generally stronger among consumers of ground (filtered or espresso) coffee and among never and former smokers. Lower subclinical inflammation may partially mediate the beneficial association between coffee consumption and lower T2D risk. Consumers of ground coffee and non-smokers may benefit the most. KEYWORDS (MESH TERMS): coffee consumptions; diabetes mellitus, type 2; inflammation; adipokines; biomarkers; mediation analysis; follow-up studies.

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.

Blood Profile, Hormones, and Telomere Responses: Potential Biomarkers in Horses Exhibiting Abnormal Oral Behavior

The high prevalence of abnormal oral behavior (AOB) in working horses has been linked to management issues and the pathophysiology of this behavior remains unclear. Therefore, this study aims to elucidate the blood profile, hormones, and telomere length responses between low and high levels of AOB among different horse working groups. A total of 207 healthy horses from various breeds were initially selected from four working groups (leisure riding, equestrian, endurance, and patrolling) and observed for the time spent on AOB. Then, six horses each with higher and lower AOB than the population means were randomly selected from each of the working groups and categorized as high and low AOB horses, respectively. Blood samples were collected for hematology, biochemistry, cortisol, ghrelin, leptin, and relative telomere length analyzes. High AOB horses notably had higher values of glucose, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatine kinase (CK) compared to low AOB horses. High AOB horses also recorded higher plasma cortisol and ghrelin, but lower leptin concentrations. Among working groups, both endurance and patrolling horses presented the highest values in sodium, potassium, chloride, phosphate, ALT, and CK. While patrolling horses had the lowest levels of urea, ALP, and albumin levels, equestrian and leisure horses recorded the highest and lowest plasma cortisol and leptin concentrations, respectively. Finally, the telomere length of endurance and patrolling horses were significantly greater than leisure and equestrian horses. The present findings suggest that AOB horses had distinctive physiological characteristics that could be linked to improper diet and a demanding workload, while ghrelin and leptin hormones could be potential biomarkers for this behavior.

Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation

Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types critical for labour onset. Macrophages secrete reactive oxygen species/pro-inflammatory cytokines, responsible for myometrial differentiation while myocytes control uterine contractions. In this study, we assessed the effect of leptin on myometrial contraction and differentiation using our validated co-culture model of human primary macrophages and myocytes. We demonstrated that leptin had a different effect on myocytes and macrophages depending on the dose. A low leptin concentration induced a tocolytic effect by preventing myocytes’ contraction, differentiation, and macrophage-induced ROS production. Additionally, leptin led to an increase in HLA-G expression, suggesting that the tocolytic effect of leptin may be driven by HLA-G, a tolerogenic molecule. Finally, we observed that recombinant HLA-G also prevented LPS-induced ROS production by macrophages. Altogether, these data provide a putative molecular mechanism by which leptin may induce immune tolerance and therefore interfere with labour-associated mechanisms. Therefore, HLA-G represents a potential innovative therapeutic target in the pharmacological management of preterm labour.

Serum leptin concentration is associated with the attainment of clinical outcomes in patients with axial spondyloarthritis treated with TNF inhibitors.

To analyse the influence of adipokines on attaining the clinical outcomes in patients with axial spondyloarthritis (axSpA) treated with TNF inhibitors (TNFi), and then, to investigate the association of patients' characteristics and adipokine concentrations. This was a longitudinal study including 110 patients with axSpA who were initiated at TNFi and were followed-up for 6 months (m). Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline and at 6 m of treatment. Clinical outcomes at 6 m of treatment were defined as remission (ASDAS <1.3) and the attainment of low disease activity (LDA; ASDAS<2.1). Leptin and adiponectin concentrations were measured in serum samples collected at baseline and after 6 m. Both leptin and adiponectin were constitutively elevated in female axSpA patients. At time of TNFi initiation, leptin concentrations were higher in patients with high body mass index (overweight or obese). On the contrary, adiponectin was higher in normalweight patients. After 6 m of TNFi treatment, 24% of patients attained remission. They had significant lower leptin concentration at baseline compared with patients who did not attain remission. Furthermore, this difference remained significant after 6 m of treatment meaning that TNFi did not modify adipokine concentration. Similar results were found considering LDA as the clinical outcome, obtained in 48% of the patients. The present study showed that low leptin concentrations were associated with attaining clinical outcomes in axSpA patients treated with TNFi. In addition, since leptin secretion by white adipocytes is enhanced during obesity and considering that TNFi do not seem to modulate its expression, obese patients should be encouraged to decrease BMI to attain a successful therapy.

Pancreas deficiency modifies bone development in the ovine fetus near term.

Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.

Anorexia Nervosa and Osteoporosis

Patients with anorexia nervosa (AN) often experience low bone mineral density (BMD) and increased fracture risk, with low body weight and decreased gonadal function being the strongest predictors of the observed bone mineral deficit and fractures. Other metabolic disturbances have also been linked to bone loss in this group of patients, including growth hormone resistance, low insulin-like growth factor-1 (IGF-1) concentrations, low leptin concentrations, and hypercortisolemia. However, these correlations lack definitive evidence of causality. Weight restoration and resumption of menstrual function have the strongest impact on increasing BMD. Other potential treatment options include bisphosphonates and teriparatide, supported by data from small clinical trials, but these agents are not approved for the treatment of low BMD in adolescents or premenopausal women with AN.

Association of bone fracture type and degree of callus formation with leptin concentration in children with long bone fractures

Background/Aim. Recent studies indicate that adipokines have an important role in bone physiology and pathology. Recent data indicate that adipokine leptin functions as a regulator of bone growth at multiple levels, systemically and locally. So far, it has been shown that leptin influences bone volume and bone mineral density in a population with metabolic and/or hormonal abnormality. Data concerning leptin values in non-obese children with fractures are scarce. Methods. This study included 93 non-obese children with long bone fractures (LBF), 14 children with short bone fractures (SBF), and 19 healthy children. Leptin concentration was determined in two blood samples (day 0 and day 21) and analyzed according to gender, fracture type, anatomical localization of the fracture, fracture topography, callus formation, and the healing outcome. Results. Children with LBF demonstrated significantly increased leptin levels compared to the control group (both day 0/day 21). In the control group, girls had significantly more leptin than boys. Leptin value was significantly influenced by anatomical localization since boys and girls with humerus fracture and girls with femur fracture had the highest average leptin concentration in the initial sample. Boys with incomplete callus formation had the highest leptin concentration (both day 0 /day 21), significantly elevated compared to boys? samples in the control group, boys? samples with an intermediary and well-formed callus, and also increased compared to the initial samples of girls with incomplete callus. Better callus formation in girls was associated with an increment of leptin concentrations in the second over the initial sample. Girls with partially and satisfactorily formed callus had significantly increased leptin concentration in the second sample (day 21) compared to the boys? group. Conclusion. Leptin concentration was significantly increased (both samples) in children with LBF compared to children with SBF and corresponding controls. Leptin concentration was highly influenced by gender. High blood leptin concentrations in boys or low leptin concentrations in girls immediately upon fracture could be used to identify groups of children with incomplete callus formation.

Leptin regulates OPG and RANKL expression in Gingival Fibroblasts and Tissues of Chronic Periodontitis Patients.

Objective: Chronic periodontitis is a bone-destructive disease affecting periodontal support structures. Although leptin has a protective effect against periodontitis, the underlying mechanism remains unclear. Therefore, this study aimed to investigate the possible role of leptin by examining its relationship with OPG and RANKL in human gingival tissues obtained from patients with chronic periodontitis.Method: Twenty-two patients with chronic periodontitis were enrolled (10 with moderate periodontitis and 12 with severe periodontitis) in the experimental group, and 12 healthy individuals were enrolled in the control group. Gingival tissue samples were collected, and the protein levels and localization of leptin, OPG, and RANKL were studied using immunohistochemistry (IHC). The staining intensities of leptin, OPG, and RANKL were correlated with the periodontal clinical index. Moreover, real-time quantitative PCR (RT-qPCR) was used to determine OPG and RANKL mRNA levels in gingival fibroblasts stimulated with gradient concentrations of leptin protein in vitro.Result: Leptin, OPG, and RANKL were located in the cytoplasm of gingival epithelial cells and the connective tissue. Leptin was widely and significantly expressed in the control group, whereas it was lightly stained in the severe group. RANKL was lightly stained in the control group, whereas it was widely and significantly expressed in the severe group. The control and the moderate groups had similar OPG levels, which were significantly higher than that in the severe group. Leptin was positively correlated with OPG(r = 0.905, p < 0.01) and negatively correlated with RANKL (r = -0.635, p < 0.01). In vitro low concentrations of leptin led to an increased OPG/RANKL mRNA ratio, whereas the opposite effect was observed at high concentrations.Conclusion: Leptin can regulate OPG and RANKL expression in gingival fibroblasts and may thus play a role in the development of chronic periodontitis by modulating the OPG/RANKL ratio.

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.

Performance, carcass and meat quality of young bulls, steers and heifers slaughtered at a common body weight

Young bulls of lean continental cattle breeds raised on concentrates achieve high weight gains during fattening but may yield carcasses with low fat cover, which may have negative effects on meat quality. Fattening steers or heifers might be an alternative for these systems, but few studies have analysed in lean breeds the impact of castration of bulls at a similar BW or the performance of females. The aim of the trial was to characterise the growth, carcass and meat quality of bulls, steers and heifers of Pirenaica breed (lean beef breed) fed on concentrates and straw until a common body weight (475 kg). Bulls had greater weight gains than steers and heifers throughout the fattening period (P < 0.001). Bulls had greater plasma IGF-I concentration throughout the fattening period but lower leptin concentration from 400 kg onwards than steers and heifers when compared at the same BW. Regarding metabolites, the concentrations of glucose, beta‑hydroxy‑butyrate, urea and non-esterified fatty acids evolved differently in bulls, steers and heifers. At slaughter, steers and heifers had deposited more fat than bulls without other differences in carcass morphology. Regarding meat quality, meat of heifers had greater lightness and lower yellowness, chroma and hue value than that of bulls and steers. Meat shear force only tended to be different amongst sexes after 14 days of ageing (P < 0.10). Heifers had greater intramuscular fat content than steers and bulls. Total saturated fatty acids were similar amongst groups but monounsaturated fatty acids proportion was greatest in heifers, intermediate in steers and lowest in bulls. Polyunsaturated fatty acid proportion was greater in bulls than in steers and heifers. Only minor effects of sex were detected by the sensory panel, with more desirable flavours and higher tenderness in heifers. Therefore, despite the faster growth of entire bulls, fattening steers and especially heifers can lead to improved fat-related meat quality traits in lean breeds.

Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population

BackgroundOrganophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exposures with birth outcomes and cord blood adipokine and insulin concentrations.MethodsWe analyzed five OPE metabolites in urine samples collected at up to three visits during pregnancy from 90 women enrolled in the ORigins of Child Health And Resilience in Development (ORCHARD) pregnancy cohort in Baltimore, MD from 2017 to 2019. To quantify the variability of metabolite concentrations during pregnancy, we calculated intraclass correlation coefficients (ICCs) for each metabolite using mixed effects regression models. Using self-reported questionnaire data collected during gestation, we assessed possible sociodemographic and environmental/behavioral predictors of each OPE metabolite using generalized estimating equations to account for repeated exposure measures. We ascertained birth outcomes of 76 offspring from medical records, including weight-for-gestational age, length, ponderal index, and gestational age. In a subset of 37 infants, we measured cord blood concentrations of leptin, adiponectin, and insulin. To account for repeated exposure measures, we used linear structural equation models to assess the relations of standard deviation (SD) increases in prenatal OPE metabolite factor scores with continuous birth outcomes and cord blood biomarker concentrations.ResultsICCs ranged from 0.09 for isopropylphenyl-phenyl phosphate (ip-PPP) to 0.59 for bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We observed little consistency in environmental or behavioral predictors of OPE exposures, although concentrations were generally lower for samples collected in the afternoon compared to morning and winter compared to other seasons. In adjusted analyses, a SD increase in BDCIPP concentration was associated with a 0.06 g/cm3 (95% CI: 0.00, 0.12) greater ponderal index. A SD increase in BDCIPP was associated with a 0.37 (95% CI: − 0.62, − 0.13) SD lower insulin concentration and 0.24 (95% CI: − 0.39, − 0.08) SD lower leptin concentration. Other OPEs were not associated with infant outcomes.ConclusionsThese findings suggest some OPEs may be metabolic disruptors warranting investigation in larger studies.

The effect of aerobic exercise training on leptin and pulmonary function tests during weight loss in men with visceral obesity

Background and aims: It has recently been documented that obesity is a global problem in all age groups, so that it affects about 250 million people in the world, accounting for 7% of the world’s population. Adipose tissue has an important role in inducing lung dysfunction through production and secretion of adipokines such as leptin. The aim of this study was to investigate the effect of a period of aerobic training on lung function indices and serum leptin levels in obese men. Methods: A total of 23 untrained obese men in Arak were recruited voluntarily for the study and randomly assigned to obese aerobic training group (Ob-AT, n=12) (45.26±2.45 years, body mass index (BMI) of 31.81±0.77 kg/m2 ) and obese control group (Ob-Cnt, n=11) (47.03±3.36 years, BMI of 31.45±0.96 kg/m2). Another normal control group (No-Cnt, n = 9) was sampled from individuals with normal weight to compare at the base level (45.1±4.1 years, BMI of 24.63±0.45 kg/m2 ). The obese exercise group participated in 12 weeks of progressive aerobic training, 3 sessions a week, 1.5 hours per session. Body composition (CT scan), leptin levels and lung function were measured before and after exercise protocol. Results: The participants with normal weight had significantly lower leptin concentration (P=0.01) and a higher lung function (P=0.016) compared to the obese participants. Moreover, the results indicated that leptin and obesity had an inverse correlation with lung function indices (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1 ]) (P≤0.05). After the aerobic activity, obesity (BMI, WHR, body fat) and lung function indices (FVC and FEV1 ) significantly decreased in the obese aerobic training group compared to the obese control group (P≤0.05). In contrast, leptin concentration significantly decreased after the aerobic exercise protocol (P=0.018). Conclusion: We found that leptin level decreased after 12 weeks of aerobic exercise in obese men and this decrease was associated with the increased lung function and profound changes in body fat. The obtained data suggest that 12-week aerobic exercise causes alterations in leptin level that plays a key role in improving lung function.