Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model.

BACKGROUND: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. METHODS: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. RESULTS: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. CONCLUSIONS: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Novel perspectives on leptin in osteoarthritis: Focus on aging.

Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration, subchondral sclerosis, synovitis, and osteophyte formation. OA is associated with disability and impaired quality of life, particularly among the elderly. Leptin, a 16-kD non-glycosylated protein encoded by the obese gene, is produced on a systemic and local basis in adipose tissue and the infrapatellar fat pad located in the knee. The metabolic mechanisms employed by leptin in OA development have been widely studied, with attention being paid to aging as a corroborative risk factor for OA. Hence, in this review, we have attempted to establish a potential link between leptin and OA, by focusing on aging-associated mechanisms and proposing leptin as a potential diagnostic and therapeutic target in aging-related mechanisms of OA that may provide fruitful guidance and emphasis for future research.

Effects of a Paleolithic diet compared to a diabetes diet on leptin binding inhibition in secondary analysis of a randomised cross-over study.

BACKGROUND: Beneficial effects from practising a Paleolithic diet as compared to a diabetes diet on weight, waist circumference, satiety, leptin, HbA1c and glucose control in randomised controlled trial participants with type 2 diabetes could be due to lower leptin resistance. Support for this hypothesis comes from an in vitro experiment that showed that digested wheat gluten, which is excluded from a Paleolithic diet, inhibits leptin from binding to its receptor, thus indicating a possible dietary cause of leptin resistance. However, the clinical relevance of the latter finding is unclear since removal of enzyme activity from the gluten digest by heat treatment also abolished leptin binding inhibition. Assessment of leptin binding inhibition in vivo is possible by comparison of total leptin levels with those of 'biologically active' leptin bound to its receptor (bioLep). OBJECTIVES: To assess the effects of a Paleolithic diet compared to a diabetes diet on leptin binding inhibition and to replicate our in vitro study. METHODS: BioLep and total leptin levels were measured in secondary analysis of fasting plasma samples from our open label random order three plus three-month long cross-over trial performed in 2005-2007, that compared a Paleolithic diet with a diabetes diet in participants with type 2 diabetes without insulin treatment (per protocol). BioLep was also measured in vitro for known recombinant leptin concentrations incubated with a series of concentrations of 10 kDa spin-filtered digested wheat gluten, with or without prior heat treatment, at 100ºC for 30 min and centrifugation. RESULTS: There was no difference between diets when comparing differences between bioLep and total leptin levels and their ratio in the 13 participants, three women and 10 men, aged 52-74 years with a mean BMI of 30 kg/m2 and a mean diabetes duration of eight years. We found no carry-over or period effect for bioLep and total leptin. In vitro, wheat gluten digest inhibited leptin binding in a dose-dependent manner but not after heat treatment. CONCLUSIONS: We found no leptin binding inhibition after the Paleolithic or diabetes diet, possibly due to its abolishment from cooking-related heat treatment of wheat gluten. TRIAL REGISTRATION: Registered on 14/02/2007 at ClinicalTrials.gov Identifier: NCT00435240.

Investigating the effect of radiofrequency electromagnetic field exposure on molecular pathways related to insulin resistance and adipogenesis in zebrafish embryos - A pilot study without quantitative exposure metrics.

In recent years, obesity has become a global problem in children and adolescents, in parallel with the rapid increase in the use of information and communication technology. Recognizing the embryonic causes of obesity may help prevent adverse adult health outcomes. In our study, we hypothesized that radiofrequency-electromagnetic field (RF-EMF) exposure during embryogenesis would affect the molecular mechanisms related to adipogenesis and insulin resistance in zebrafish. To achieve this, we set up a system that emits RF-EMF in the 900 MHz band and subjected zebrafish embryos to its RF-EMF. We created two groups in which we exposed 30 min (EMF-30) and 60 min (EMF-60) per day, and a control group that was not exposed to RF-EMF. We ended the exposure at 96 hpf and analyzed the expression of lepa, ins, and pparg that are involved in the regulation of glucose and lipid metabolism. In addition, we analyzed oxidative stress parameters, embryonic development, and locomotor activity. We found decreased mRNA transcript abundance of lepa, ins, pparg, and activities of superoxide dismutase and acetylcholine esterase, along with increased lipid peroxidation (LPO), nitric oxide (NO), and glutathione S-transferase (GST). Locomotor activity increased in the EMF-30 group and decreased in the EMF-60 group. Our results showed that exposure to RF-EMF during the embryonic period disrupted the molecular pathways related to insulin resistance and adipogenesis in zebrafish. However, due to limited available resources, we were not able to appropriately quantify the actual RF exposure strength of the samples. Hence the results reported here should only be seen as preliminary, and further studies employing high quality exposure apparatus and dosimetry should be carried out in future.

History and future of leptin: Discovery, regulation and signaling.

The cloning of leptin 30 years ago in 1994 was an important milestone in obesity research. Prior to the discovery of leptin, obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause severe obesity, and it is now recognized that obesity is caused mostly by a dysregulation of central neuronal circuits. Since the discovery of the leptin-deficient obese mouse (ob/ob) the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, we have learned much about leptin and its action in the central nervous system. The first hope that leptin would cure obesity was quickly dampened because humans with obesity have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint to understand how neuronal circuits control energy homeostasis. Our expanding understanding of leptin function, interconnection of leptin signaling with other systems and impact on distinct physiological functions continues to guide and improve the development of safe and effective interventions to treat metabolic illnesses. This review highlights past concepts and current emerging concepts of the hormone leptin, leptin receptor signaling pathways and central targets to mediate distinct physiological functions.

Clinical and biochemical responses to treatment of uncomplicated severe acute malnutrition: a multicenter observational cohort from the OptiDiag study.

BACKGROUND: Severe acute malnutrition (SAM) can be diagnosed using weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC). Although some favor using MUAC alone, valuing its presumed ability to identify children at greatest need for nutritional care, the functional severity and physiological responses to treatment in children with varying deficits in WHZ and MUAC remain inadequately characterized. OBJECTIVE: We aimed to compare clinical and biochemical responses to treatment in children with 1) both low MUAC and low WHZ, 2) low MUAC-only, and 3) low WHZ-only. METHODS: A multicenter, observational cohort study was conducted in children aged 6-59 mo with nonedematous, uncomplicated SAM in Bangladesh, Burkina Faso, and Liberia. Anthropometric measurements and critical indicators were collected 3 times during treatment; metrics included clinical status, nutritional status, viability, and serum leptin, a biomarker of mortality risk in SAM. RESULTS: Children with combined MUAC and WHZ deficits had greater increases in leptin levels during treatment than those with low MUAC alone, showing a 34.4% greater increase on the second visit (95% confidence interval [CI]: 7.6%, 43.6%; P = 0.02) and a 34.3% greater increase on the third visit (95% CI: 13.2%, 50.3%; P = 0.01). Similarly, weight gain velocity was higher by 1.56 g/kg/d in the combined deficit group (95% CI: 0.38, 2.75; P = 0.03) compared with children with low MUAC-only. Children with combined deficits had higher rates of iron deficiency and wasting while those with low WHZ alone and combined deficits had higher rates of tachypnea and pneumonia during treatment. CONCLUSIONS: Given the comparable treatment responses of children with low WHZ alone and those with low MUAC alone, and the greater vulnerability at admission and during treatment in those with combined deficits, our findings support retaining WHZ as an independent diagnostic and admission criterion of SAM, alongside MUAC. This trial was registered at www. CLINICALTRIALS: gov/study/NCT03400930 as NCT03400930.

Appetite hormones, neuropsychological function and methylphenidate use in children with attention-deficit/hyperactivity disorder.

Appetite hormones may play a significant role in neuronal excitability and synaptic plasticity and may also affect brain function development. This study aimed to explore the role of appetite hormones in attention deficit/hyperactivity disorder (ADHD), including aspects of pathophysiology, pharmacotherapy, and side effects. We recruited 119 patients with ADHD who were undergoing methylphenidate treatment (ADHD+MPH), 77 unmedicated ADHD patients (ADHD-MPH), and 87 healthy controls. Blood samples were collected from all participants to examine serum levels of orexin A, ghrelin, leptin, and adiponectin. Behavioral symptoms were assessed using the Swanson, Nolan, and Pelham Rating Scale, and visual and auditory attention were evaluated using computerized neuropsychological tests. The side effects of methylphenidate treatment were measured using Barkley's Side Effects Rating Scale. Orexin levels in the control group were significantly higher than in the ADHD-MPH (p=0.037) and ADHD+MPH (p<0.001) groups; additionally, orexin levels in the ADHD-MPH group were significantly higher than in the ADHD+MPH group (p=0.032). Leptin levels in both the ADHD+MPH (p=0.011) and ADHD-MPH (p=0.011) groups were significantly lower than in the control group. Ghrelin levels were positively associated with auditory attention across all ADHD groups (p=0.015). Furthermore, ghrelin levels were positively correlated with methylphenidate dosage (p=0.024), and negatively correlated with methylphenidate side effects (p=0.044) in the ADHD+MPH group. These findings provide further insight into the relationships between appetite hormones, pharmacotherapy, and ADHD. Orexin A and leptin are associated with the etiology of ADHD, while orexin A and ghrelin play important roles in attention deficits and methylphenidate usage in ADHD.

Negative feedback control of hypothalamic feeding circuits by the taste of food.

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here, we show that hunger-promoting agouti-related peptide (AgRP) neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin-receptor-expressing neurons in the dorsomedial hypothalamus (DMHLepR) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption.

Predictors of weight and waist gain in US South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.

Background: Weight and waist gain are significant concerns in adulthood. Both weight and waist gain are particularly important among South Asians, known to have an increased risk of developing chronic cardiometabolic complications at any body mass index compared to other racial and ethnic groups. The aim of this study was to investigate factors predicting weight and waist gain in a longitudinal cohort of South Asians living in the US (United States). Methods: This was a prospective analysis using data from exam 1 (2010-2013) and exam 2 (2015-2018) of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, a prospective cohort study of South Asians (recruited from San Francisco and Chicago), with a mean 4.8 years of follow-up. Results: Of 634 participants studied (42.7 % women, mean age 55 years, BMI 25.7 kg/m2, weight 70.4 kg at exam 1), 34.7 % had gained ≥5 % weight and 32.3 % gained ≥5 % waist at exam 2. In the adjusted models, older age, higher number of years of US residence, and having diabetes were associated with lower odds of weight gain; being female and having higher adiponectin were associated with higher odds of weight gain. Being female and being employed full/part time or being retired predicted lower likelihood of waist gain. Being single, separated/divorced, having a higher leptin and a higher C-reactive protein level predicted higher likelihood of waist gain. Conclusions: The current study identified several social, demographic, and clinical factors that can serve as targets for obesity interventions among US South Asians. In addition, this study also raises hypotheses about associations of adipokine levels with weight and waist gain.

Hypomethylated leptin receptor reduces cerebral ischaemia-reperfusion injury by activating the JAK2/STAT3 signalling pathway.

OBJECTIVE: To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR). METHODS: The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia-reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels. RESULTS: The optimal leptin concentration for exerting neuroprotective effects against ischaemia-reperfusion injury in PC12 cells was 200 ng/ml in vitro, but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used. CONCLUSION: Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2/STAT3 and apoptotic signalling pathways.

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.

INTRODUCTION: Neuropeptide 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 METHODS: In 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. RESULTS: Leptin 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). CONCLUSION: Assessment 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.

The impact of consuming different types of high-caloric fat diet on the metabolic status, liver, and aortic integrity in rats.

Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson's trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.

Carotid body interoception in health and disease.

Interoception entails perceiving or being aware of the internal state of the body, playing a pivotal role in regulating processes such as heartbeat, digestion, glucose metabolism, and respiration. The carotid body (CB) serves as an interoceptive organ, transmitting information to the brain via its sensitive nerve, the carotid sinus nerve, to maintain homeostasis. While traditionally known for sensing oxygen, carbon dioxide, and pH levels, the CB is now recognized to possess additional interoceptive properties, detecting various mediators involved in blood pressure regulation, inflammation, and glucose homeostasis, among other physiological functions. Furthermore, in the last decades CB dysfunction has been linked to diseases like sleep apnea, essential hypertension, and diabetes. In this review manuscript, we make a concise overview of the traditional interoceptive functions of the CB, acting as a sensor for oxygen levels, carbon dioxide levels, and pH, and introduce the novel interoceptive properties of the CB related to vascular, glucose and energy regulation. Additionally, we revise the contribution of the CB to the onset and progression of metabolic diseases, delving into the potential dysfunction of its interoceptive metabolic functions as a contributing factor to pathophysiology. Finally, we postulate the use of therapeutic interventions targeting the metabolic interoceptive properties of the CB as a potential avenue for addressing metabolic diseases.

Impact of Resistance and Endurance Training on Ghrelin and Plasma Leptin Levels in Overweight and Obese Subjects.

Exercise training is a valuable tool for improving body weight and composition in overweight or obese adults, which leads to a negative energy balance. It is relevant to consider whether exercise can help people lose weight or prevent weight gain because any energy expended in exercise increases the severity of hunger and promotes food consumption. Over the past decade, the identification of the circulating peptide ghrelin, which alerts the brain to the body's nutritional state, has significantly expanded our understanding of this homeostatic mechanism that controls appetite and body weight. To shed more light on this issue, we decided to investigate the effects of resistance and endurance training on plasma ghrelin and leptin levels. In addition, we sought to understand the mechanisms by which acute and chronic exercise can regulate hunger. This review analyzes studies published in the last fifteen years that focused on changes suffered by ghrelin, leptin, or both after physical exercise in overweight or obese individuals. Most studies have shown a decrease in leptin levels and an increase in ghrelin levels in these cases. Exercise regimens that support weight maintenance need further investigation.

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age.

INTRODUCTION: We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults. METHODS: We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols. RESULTS: Higher sOB-R was associated with lower fractional anisotropy (FA, ß = -0.114 ± 0.02, p < 0.001), and higher free water (FW, ß = 0.091 ± 0.022, p < 0.001) and peak-width skeletonized mean diffusivity (PSMD, ß = 0.078 ± 0.021, p < 0.001). Correspondingly, higher FLI was associated with higher FA (ß = 0.115 ± 0.027, p < 0.001) and lower FW (ß = -0.096 ± 0.029, p = 0.001) and PSMD (ß = -0.085 ± 0.028, p = 0.002). DISCUSSION: Higher leptin bioavailability was associated with better white matter (WM) integrity in healthy middle-aged adults, supporting the putative neuroprotective role of leptin in late-life dementia risk. HIGHLIGHTS: Higher leptin bioavailability was related to better preservation of white matter microstructure. Higher leptin bioavailability during midlife might confer protection against dementia. Potential benefits might be even stronger for individuals with visceral obesity. DTI measures might be sensitive surrogate markers of subclinical neuropathology.

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.

Changes in Circulating Adipokine Levels in COVID-19 Patients.

Objective: The COVID-19 pandemic has posed significant global health challenges. Despite extensive research efforts, the inflammatory response triggered by SARS-CoV-2 remains to be further explored and understood. Our study aims to examine the changes in serum concentrations of pro-inflammatory adipokines-visfatin and leptin-in COVID-19 patients in relation to a healthy control group. Patients/Materials/Subjects and Methods: The study consisted of forty COVID-19 patients and twenty-four healthy patients in the control group. Two serum samples were collected: upon admission and on the seventh day of hospitalization. Concentrations of visfatin and leptin in the serum, alongside routine biochemical parameters, were measured using enzyme immunoassay or enzyme-linked immunosorbent assay kits. The Shapiro-Wilk test was used to assess normality. Differences between independent groups were compared using the Mann-Whitney U test and Kruskal-Wallis ANOVA. Correlations were evaluated with Spearman's rank correlation coefficient. Results: Our findings revealed significantly lower visfatin levels in COVID-19 patients compared to the control group upon admission (4.29 ng/mL, (3.0-6.88 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p < 0.001 for visfatin 1 and 52.05 ng/mL, (31.2-69.66 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p = 0.048 for visfatin 2). The visfatin level of COVID-19 patients returned to the normal levels, established in the control group. However, there was no significant difference in leptin levels between the two groups (p = 0.270 for leptin 1 and p = 0.129 for leptin 2). There was a positive correlation between BMI and leptin concentration (r = 0.66 and p = 0.00). Moreover, it was discovered that COVID-19 independently reduces visfatin levels during the first day of illness. Conclusions: The results of our research suggest that the onset of COVID-19 infection is correlated to visfatin levels. Association with leptin levels remains inconclusive. Further research is imperative to elucidate the intricate role of visfatin and leptin in SARS-CoV-2 infection and their potential as biomarkers for COVID-19 severity and prognosis.

Resistin and In-Hospital Mortality in Patients with Acute Ischemic Stroke: A Prospective Study.

Background/Objectives: Understanding the prognostic factors of acute ischemic stroke (AIS) is essential for improving patient outcomes. The aim of this study was to establish the predictive role of plasmatic resistin and leptin on short-term mortality in adult patients with a first episode of AIS. Methods: This study enrolled 277 patients who were consecutively hospitalized for AIS. Demographic data, cardiovascular risk, comorbidities, and laboratory tests were collected. Death was noted if it occurred during hospitalization. Results: Death was recorded in 33 (11.9%) patients. Conducting multivariate analysis, the following variables were independent variables associated with in-hospital mortality: a resistin value of >11 ng/mL (OR 10.81 (95%CI 2.31;50.57), p = 0.002), a lesion volume of >18.8 mL (OR 4.87 (95%CI 1.87;12.67), p = 0.001), a NIHSS score of >7 (OR 5.88 (95%CI 2.01;17.16), p = 0.001), and the presence of IHD (OR 4.33 (95%CI 1.66;11.27), p = 0.003). This study has some limitations: single-center design (which may affect the generalizability of the results) and the potential impact of the COVID-19 pandemic on patient outcomes. Conclusions: This study demonstrated that resistin is a significant predictor of in-hospital mortality in AIS patients. Other established factors, such as a high NIHSS score, large lesion volume, and the presence of IHD, were reaffirmed as important predictors.

Correlation of Adiponectin and Leptin with Anthropometrics and Behavioral and Physical Performance in Overweight and Obese Chinese College Students.

The aim of this study is to assess the relationship of leptin (LEP) and adiponectin (ADPN) with other circulating fat markers, physical capacity, behaviors, and anthropometric indices in a population of overweight and obese Chinese university students. LEP and ADPN levels, as well as behavioral, anthropometric, biochemical, and performance characteristics, were measured. METHOD: A total of 17 anthropometric parameters, 8 questionnaires (investigating quality of life, sleep, eating, perceived functioning, stress, and depression), 9 biochemical parameters, and 12 functional parameters were investigated. RESULTS: In contrast to previous studies, our work found an unusually strong relationship between LEP and ADPN (r = 0.961, p = 0.000) that can be related to ethnicity. We also found that LEP and ADPN were associated with stress and bodily pain. A total of 12 anthropometric measures were also associated with LEP/ADNP levels. Moreover, LEP and ADPN were found to be related to lower limb, hand, and abdominal strength; blood pressure; and basic metabolism. However, we did not find associations with sleep; eating habits; or cardiovascular fitness, which was measured in the form of resting heart rate and VO2max. CONCLUSION: This study reveals new relationships of LEP and ADPN with selected anthropometric and behavioral parameters in obese Chinese college students.

Interleukin-1ß Signaling Contributes to Cell Cycle Arrest and Apoptotic Cell Death by Leptin via Modulation of AKT and p38MAPK in Hepatocytes.

Leptin, an adipose tissue-derived hormone, has exhibited the potent hepatotoxic effects. However, the underlying molecular mechanisms are not fully understood. In this study, we have elucidated the mechanisms by which leptin exerts cytotoxic effects in hepatocytes, particularly focusing on the role of interleukin-1ß (IL-1ß) signaling. Leptin significantly induced maturation and secretion of IL-1ß in cultured rat hepatocytes. Interestingly, inhibition of IL-1ß signaling by pretreatment with an IL-1 receptor antagonist (IL-1Ra) or gene silencing of type I IL-1 receptor (IL-1R1) markedly abrogated leptin-induced cell cycle arrest. The critical role of IL-1ß signaling in leptin-induced cell cycle arrest is mediated via upregulation of p16, which acts as an inhibitor of cyclin-dependent kinase. In addition, leptin-induced apoptotic cell death was relieved by inhibition of IL-1ß signaling, as determined by annexin V/7-AAD binding assay. Mechanistically, IL-1ß signaling contributes to apoptotic cell death and cell cycle arrest by suppressing AKT and activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Involvement of IL-1ß signaling in cytotoxic effect of leptin was further confirmed in vivo using hepatocyte specific IL-1R1 knock out (IL-1R1 KO) mice. Essentially similar results were obtained in vivo, where leptin administration caused the upregulation of apoptotic markers, dephosphorylation of AKT, and p38MAPK activation were observed in wild type mice liver without significant effects in the livers of IL-1R1 KO mice. Taken together, these results demonstrate that IL-1ß signaling critically contributes to leptin-induced cell cycle arrest and apoptosis, at least in part, by modulating p38MAPK and AKT signaling pathways.