Leptin Expression Research Articles

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Aspalathus linearis-a plant widely consumed as Rooibos tea-are increasingly being investigated for their positive effects on various health issues including inflammation. The aim of our study was to examine the effect of Rooibos extract on obesity and the associated low-grade chronic inflammatory state by testing antioxidant activity, cytokine secretions, macrophage polarization and the differentiation of human adipocytes through the development of adipospheroids. Rooibos extract significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFN-γ, IL-12, IL-2 and IL-17a) in human leukocytes. Additionally, Rooibos extract down-regulated LPS-induced macrophage M1 polarization, shown by a significant decrease in the expression of pro-inflammatory cytokines: TNFα, IL-8, IL-6, IL-1β and CXCL10. In addition, Rooibos inhibited intracellular lipid accumulation and reduced adipogenesis by decreasing the expression of PPARγ, Ap2 and HSL in adipospheroids. A significant decrease in leptin expression was noted and this, more interestingly, was accompanied by a significant increase in adiponectin expression. Using a co-culture system between macrophages and adipocytes, Rooibos extract significantly decreased the expression of all studied pro-inflammatory cytokines and particularly leptin, and increased adiponectin expression. Thus, adding Rooibos tea to the daily diet is likely to prevent the development of obesity associated with chronic low-level inflammation.

SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression

Adipose tissue modulates energy homeostasis by secreting leptin, but little is known about the factors governing leptin production. We show that succinate, long perceived as a mediator of immune response and lipolysis, controls leptin expression via its receptor SUCNR1. Adipocyte-specific deletion of Sucnr1 influences metabolic health according to nutritional status. Adipocyte Sucnr1 deficiency impairs leptin response to feeding, whereas oral succinate mimics nutrient-related leptin dynamics via SUCNR1. SUCNR1 activation controls leptin expression via the circadian clock in an AMPK/JNK-C/EBPα-dependent manner. Although the anti-lipolytic role of SUCNR1 prevails in obesity, its function as a regulator of leptin signaling contributes to the metabolically favorable phenotype in adipocyte-specific Sucnr1 knockout mice under standard dietary conditions. Obesity-associated hyperleptinemia in humans is linked to SUCNR1 overexpression in adipocytes, which emerges as the major predictor of adipose tissue leptin expression. Our study establishes the succinate/SUCNR1 axis as a metabolite-sensing pathway mediating nutrient-related leptin dynamics to control whole-body homeostasis.

Association of Immunohistochemistry Leptin Expression with Plasma ELISA Leptin Levels in Invasive Breast Ductal Carcinoma: A Cross-Sectional Study

Association of Immunohistochemistry Leptin Expression with Plasma ELISA Leptin Levels in Invasive Breast Ductal Carcinoma: A Cross-Sectional Study

Leptin and leptin receptor expression as biomarkers for breast cancer: a retrospective study

BackgroundEffective screening and treatment have reduced the number of women dying from breast cancer (BC). However, the long-term sequelae of BC treatment and psychosocial factors seriously affect the life quality of BC patients and survivors. Therefore, the discovery and application of targeted biomarkers to improve the functional outcome and life quality of BC patients is necessary.AimsTo explore the impact of leptin (LEP)/ leptin receptor (LEPR) expression on occurrence and survival of BC.MethodsTotally 132 primary BC and 66 non-BC patients who underwent surgery in department of breast surgery in Shanxi Cancer Hospital from January to October in 2009 were enrolled in this retrospective study. LEP and LEPR were examined in BC tissues, benign breast tissues, para-carcinoma tissues using immunohistochemical staining. Kaplan–Meier curve was generated to test survival time.ResultsThe high level expression of LEP and LEPR in BC tissues were significantly higher than that in benign breast tissues and in para-carcinoma tissues (all P < 0.05). The LEP expression in patients with lymph node metastases was significantly higher than that in patients without lymph nodes metastases (P = 0.002). LEPR expression was correlated with higher Ki-67 rate (P = 0.002). LEP and LEPR both had no impact on survival (all P > 0.05).ConclusionsHigh LEP/LEPR expression were risk factors for occurrence of BC, but without impact on survival.

Timosaponin AIII attenuates precocious puberty in mice through downregulating the hypothalamic-pituitary-gonadal axis.

Precocious puberty (PP) has increasingly become a social concern. This study aimed to investigate the effect of timosaponin AIII (TAIII) on the precocious puberty and its possible mechanisms in mice. Four groups of mice consisting of controls that received saline or TAIII, a model that received leptin to induce precocious puberty (PP), and leptin+TAIII (the leptin model treated with TAIII) were used to determine the effect of TAIII on PP. Pathological and cytological examinations were conducted to investigate the signs and onset of PP and the development of reproductive organs. The level of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were determined using enzyme-linked immunosorbent assay (ELISA). The expression of genes related to the hypothalamic-pituitary-gonadal axis (HPGA) was assessed using qRT-PCR and Western blotting. Bone mineral density (BMD) was determined using high resolution peripheral quantitative computed tomography. In mice treated with leptin, earlier vaginal opening and estrus were observed, as well as the increased ovarian and uterine weight, total uterine cross-sectional size, number of corpora lutea, and elevated serum sex hormone levels and HPGA expression. On the other hand, TAIII treatment delayed the vaginal opening and vaginal estrus to 32.1 and 37.5 days after birth, and delayed the development of reproductive organs, leading to significantly smaller uterus and ovary size, less corpora lutea and low BMD (P<0.05). In addition, the serum levels of LH, FSH and E2 were significantly reduced (P<0.05) and so was the expression of HPGA and leptin genes (P<0.05). Our experimental data demonstrated that TAIII has activity against leptin-induced PP activity and may attenuate PP by reducing reproductive hormones and deactivating the hypothalamic-pituitary-gonadal axis through downregulating leptin expression.

Lipoxin A4 methyl ester attenuated ketamine-induced neurotoxicity in SH-SY5Y cells via regulating leptin pathway

Ketamine, the widely used intravenous anesthetic, has been reported to cause neurotoxicity and disturbs normal neurogenesis. However, the efficacy of current treatment strategies targeting ketamine's neurotoxicity remains limited. Lipoxin A4 methyl ester (LXA4 ME) is relatively stable lipoxin analog, which serves an important role in protecting against early brain injury. The purpose of this study was to investigate the protective effect of LXA4 ME on ketamine-caused cytotoxicity in SH-SY5Y cells, as well as the underlying mechanisms. Cell viability, apoptosis and endoplasmic reticulum stress (ER stress) were detected by adopting experimental techniques including CCK-8 assay, flow cytometry, western blotting and transmission electron microscope. Furthermore, examining the expression of leptin and its receptor (LepRb), we also measured the levels of activation of the leptin signaling pathway. Our results showed that LXA4 ME intervention promoted the cell viability, inhibited cell apoptosis, and reduced the expression of ER stress related protein and morphological changes induced by ketamine. In addition, inhibition of leptin signaling pathway caused by ketamine could be reversed by LXA4 ME. However, as the specific inhibitor of leptin pathway, leptin antagonist triple mutant human recombinant (leptin tA) attenuated the cytoprotective effect of LXA4 ME against ketamine-induced neurotoxicity. In conclusion, our findings demonstrated LXA4 ME could exert a neuroprotective effect on ketamine-induced neuronal injury via activation of the leptin signaling pathway.

Effect of customised supplement on haemato-biochemical profile, serum minerals, metabolic hormones, antioxidant capacity and gene expression in crossbred calves

Present experiment examined the supplementary effect of a tailor-made supplement to farmers’-based diet in crossbred calves. Male crossbred calves (15) were randomly allocated in 3 dietary treatments consisting of 5 calves in each. The dietary treatments were: Control- cereal straw-based diet with concentrate mixture as per the farmers’ practices; CS (customised supplement)- control diet with additional customised supplement @ 0.25% of BW; SD-standard diet. Serum glucose was higher in SD than control, however, CS had an intermediate response. The serum macro (Ca and i-P) and trace (Zn, Cu, Fe and Mn) minerals were higher in SD and CS than control. The serum T3 and T4 hormones were significantly higher in SD and CS than control group. The serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were significantly higher in SD than control groups, however, SD had an intermediate position. The total antioxidant capacity (TAOC) was significantly higher in SD and CS than control group. The relative mRNA expression of cytokines, viz. IL-2 and IL-4 was significantly higher in SD and CS than control group. The relative mRNA expression of leptin (LEP) was significantly higher and ghrelin (GHRL) was significantly lower in SD than control group, however, CS had a transitional position. Thus, it can be concluded that supplementation of the customised supplement (@ 0.25% BW) to farmers’-based diet significantly improved the serum glucose concentration, metabolic hormone profile, antioxidant capacity and relative mRNA expression of cytokines and genes involved in energy metabolism in crossbred calves.

Abstract P5-14-01: Transcriptomic insights into lobular breast cancer biology: a retrospective analysis of the MINDACT clinical trial

Abstract Background: Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer after invasive breast cancer of no special type (NST). In this retrospective analysis of the MINDACT trial, we aimed at identifying/refining the transcriptomic differences between: 1) estrogen receptor positive/HER2-negative (ER+/HER2-) ILC versus ER+/HER2- NST, 2) classic and non-classic ER+/HER2- ILC, and, 3) recurring and non-recurring ER+/HER2- ILC in the subgroup of patients with a low clinical and low genomic (cL/gL) risk (as defined by a modified version of Adjuvant Online! and the 70-gene signature). Patients and methods: Central pathology review was performed for histological subtype, grade and Ki67 (G.V.) for 5929/6693 (88.6%) of the patients included in the MINDACT trial (NCT00433589). Analysis of transcriptomic data adjusted for age and grade was performed using the R/Bioconductor package ‘limma’ to identify differentially expressed genes (DEGs). DEGs having absolute log-fold change (logFC)≥ 0.2 and FDR-adjusted p-value (q-value) &amp;lt; 0.05 were considered. Gene set enrichment analyses (GSEA) of MSigDB hallmark gene sets were performed. Adjusted Cox regression models were used to evaluate the association of these hallmarks with disease free survival (DFS) and distant recurrence free survival (DRFS). Results: After central pathological review, 464 patients with ER+/HER2- ILC and 3798 patients with ER+/HER2- NST were identified. Patients with ILC were significantly older at diagnosis, had larger tumors, less axillary nodal involvement, more grade 2 tumors than patients with NST. At the transcriptomic level, we observed a high number of DEGs between these 2 subgroups, confirming their distinct phenotype. CDH1, the gene coding for E-cadherin, was as expected the most highly overexpressed gene in NST versus ILC. We further observed an increased expression of leptin (LEP), leptin receptor (LEPR), lipoprotein lipase (LPL), and the fatty acid transporter CD36 in ILC. This could suggest that ILC relied on increased lipid uptake thanks to the increased contact of ILC tumor cells with the adipocytes. IGF1 was also overexpressed in ILC versus NST, as a potential consequence of high LEP and high LEPR expression. Differences were also evident with regard to the extracellular matrix (ECM), with many collagens, matrix metalloproteinases (MMPs) and other key enzymes (e.g. LOXL1) being differentially expressed. We confirmed a decreased ER-signaling and increased PI3K/Akt signaling in ILC versus NST. Out of the 464 ER+/HER2- ILC tumors, 253 (55%) were classic ILC and 211 (45%) non-classic ILC. There were more grade 3 tumors, more highly proliferative tumors and more nodal involvement in patients with non-classic versus classic ILC. At the transcriptomic level, differences were subtler than the differences seen above. Still, a significant enrichment of the hallmarks related to cell cycle in the non-classic ILC, and of the hallmarks related to epithelial-to-mesenchymal transition, hypoxia, adipogenesis and IL6/JAK/STAT3 signaling in classic ILC was observed. Finally, 216/464 patients with ER+/HER2- ILC (47%) were assigned to the cL/gL risk group and did not receive chemotherapy. 28/216 of these patients (13%) relapsed (DFS, median FU: 8.7 years). Enrichment of hallmarks related to apoptosis, inflammatory response, hypoxia and oncogenic signaling (PI3K/Akt, Ras, c-Myc) was associated with worse survival. Conclusion: This represents, to the best of our knowledge, the largest set of gene expression data for patients with ILC, issued from a clinical trial where histology was reviewed centrally. These results could be used to personalize treatment for patients with ILC. This project is funded by the Breast Cancer Research Foundation. Citation Format: Christine Desmedt, Ha-Linh Nguyen, François Richard, Sabine Linn, Otto Metzger, Coralie Poncet, Jelle Wesseling, Florentine Hilbers, Kim Aalders, Mauro Delorenzi, Suzette Delaloge, Jean-Yves Pierga, Etienne Brain, Suzan Vrijaldenhoven, Peter A Neijenhuis, Karen Van Baelen, Marion Maetens, Emiel Rutgers, Martine Piccart, Laura Van ’t Veer, Giuseppe Viale, Fatima Cardoso. Transcriptomic insights into lobular breast cancer biology: a retrospective analysis of the MINDACT clinical trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-01.

Protective effect of Anoectochilus burmannicus extracts and its active compound, kinsenoside on adipocyte differentiation induced by benzyl butyl phthalate and bisphenol A

Benzyl butyl phthalate (BBP) and bisphenol-A (BPA) are obesogens that have been reported to be associated with obesity. Inhibition of their adipogenic activity could decrease the risk of obesity-related metabolic disorders. This study hypothesized that Anoectochilus burmannicus ethanolic extract (ABE) which has been previously reported its anti-inflammation property and its known active compound, kinsenoside (Kin) abrogate BBP- and BPA-induced adipogenesis. ABE and Kin markedly suppress both BBP- and BPA-stimulated adipogenesis with different modulations on adipogenic-gene expression including C/EBPα, PPARγ, adiponectin, and leptin in 3T3-L1. BBP induced C/EBPα, adiponectin, and leptin mRNA expressions and slightly increased PPARγ mRNA level, whereas BPA markedly induced PPARγ and adiponectin mRNA levels. ABE significantly decreased the expression of C/EBPα and leptin, but not PPARγ and adiponectin in the BBP-treated cells. In the BPA-treated cells, ABE significantly decreased the mRNA expression of C/EBPα and PPARγ, but not adiponectin and leptin. Interestingly, Kin significantly overcame BBP- and BPA-induced C/EBPα, PPARγ, adiponectin, and leptin expressions. This study first provides evidence to support the health benefits of this plant, especially for people exposed to obesogens. Besides, this finding would encourage the conservation and culture of this orchid for development as an economic plant and healthy food.

Soy Lecithin in High-Fat Diets Exerts Dual Effects on Adipose Tissue Versus Ileum.

Lipopolysaccharides and their transporters, LBP and sCD14, are involved in systemic inflammation following a high-fat diet. Natural emulsifiers such as soy lecithin, rich in soybean polar lipids (SPL), are often used by the food industry but little is known about effects of associating SPL with different oils. Thus, this study investigates the effects of 4 weeks feeding of palm (P) or rapeseed (R) oil-enriched diets with or without SPL in mice, on white adipose tissue (WAT) inflammation, on ileum permeability, and on microbiota composition. When SPL are associated with rapeseed oil, a greater gene expression of leptin and inflammation in WAT is observed compared to P-SPL. In ileum, R-SPL group results in a lower expression of TLR4, IAP that detoxify bacterial LPS and tight junction proteins than R group. In turn, the gene expression of Reg3β and Reg3γ, which have antimicrobial activity, is higher in ileum of R-SPL group than in R group. SPL in rapeseed oil increases specific bacterial species belonging to Lachnospiraceae, Alistipes, and Bacteroidales. The incorporation of SPL in a diet with rapeseed oil exerts differential effect on WAT and ileum, with respectively an inflammation of WAT and an antimicrobial activity in ileum, associated with specific microbiota changes.

Reproductive phase-dependent and sexually dimorphic expression of leptin and its receptor in different parts of brain of spotted snakehead Channa punctata.

The reproductive phase-wise leptin (lep) and its receptor (lepr) expression in different parts of the brain of adult male and female spotted snakehead Channa punctata reveals sexual dimorphism in the brain leptin system. In anterior, middle and posterior parts of the brain of males, a maximum lep was observed in resting, spawning and postspawning reproductive phases, respectively. In females, a high level of lep was seen during the preparatory phase in the anterior brain, preparatory and postspawning phases in the middle brain and resting and postspawning phases in the posterior brain. Nonetheless, the transcript level of lepr was recorded highest during the spawning phase, irrespective of sex and region of the brain. Regardless of the reproductive state of fishes, lep and lepr were seen considerably high in middle and posterior parts of male brain than that of female, implying the involvement of factors other than sex steroids for sex-related variation in the leptin system in these regions of the brain. Nonetheless, no sex difference was evidenced in the expression of either ligand or its receptor in the anterior brain. In summary, the presence of lep and lepr in different regions of the brain and variation in their expression depending on sex and reproductive phases raise the possibility of pivotal actions of leptin in influencing neuronal circuitry and thereby reproductive functions.

Localization of FGF21 Protein and Lipid Metabolism-Related Genes in Camels

With the ability to survive under drought and chronic hunger, camels display a unique regulation characteristic of lipid metabolism. Fibroblast growth factor (FGF) 21 is a peptide hormone that regulates metabolic pathways, especially lipid metabolism, which was considered as a promising therapeutic target for metabolic diseases. To understand the FGF21 expression pattern and its potential relationship with lipid metabolism in camels, this study investigated the distribution and expression of FGF21, receptor FGFR1, and two lipid metabolism markers, leptin and hormone-sensitive lipase (HSL), using an immunohistochemistry (IHC) assay. The results showed that FGF21 was widely expressed in camel central nerve tissue and peripheral organs but absent in lung and gametogenic tissue, including the testis, epididymis, and ovary. In striated muscle, FGF21 is only present at the fiber junction. FGFR1 is expressed in almost all tissues and cells, indicating that all tissues are responsive to FGF21 and other FGF-mediated signals. Leptin and HSL are mainly located in metabolic and energy-consuming organs. In the CNS, leptin and HSL showed a similar expression pattern with FGFR1. In addition, leptin expression is extremely high in the bronchial epithelium, which may be due to its role in the immune responses of respiratory mucosa, in addition to fat stores and energy balance. This study found that FGF21 showed active expression in the nervous system of camels, which may be related to the adaptability of camels to arid environments and the specific regulation of lipid metabolism. This study showed a special FGF21-mediated fat conversion pattern in camels and provides a reference for developing a potential therapeutic method for fat metabolism disease.

Pediococcus pentosaceus PR-1 modulates high-fat-died-induced alterations in gut microbiota, inflammation, and lipid metabolism in zebrafish.

Obesity is a health issue worldwide. This study aimed to evaluate the beneficial effects of Pediococcus pentococcus PR-1 on the modulating of gut microbiota, inflammation and lipid metabolism in high-fat-diet (HFD)-fed zebrafish. Adult zebrafish were fed a commercial (C), high fat (H, 25% fat), probiotic (P, 106 CFU/g), or high fat with probiotic (HP) diets twice daily for 5 weeks. Gut microbiota were analysed using 16S rRNA gene sequencing. Gene expressions of intestinal cytokine, intestinal TJ protein, and liver lipid metabolism were analysed by quantitative real-time polymerase chain reaction. Biochemical and histological analysis were also performed. P. pentosaceus PR-1 reduced body weight and BMI, indicating its anti-obesity effect. The 16S rRNA sequencing results showed HFD induced a distinct gut microbiota structure from C group, which was restored by probiotic. P. pentosaceus PR-1 improved gut health by decreasing the abundance of Ralstonia and Aeromonas which were increased induced by HFD. Moreover, probiotic restored abundance of Fusobacteria, Cetobacterium and Plesiomonas, which were decreased in HFD-fed zebrafish. The results of quantitative real-time polymerase chain reaction showed probiotic suppressed HFD-induced inflammation by decreasing the expressions of IL-1b and IL-6. Levels of hepatic TNF-α, IL-1ß, and IL-6 were reduced by probiotic in HFD-fed zebrafish. Probiotic also ameliorated gut barrier function by increasing the expressions of occludin, Claudin-1, and ZO-1. Probiotic exerted anti-adipogenic activity through regulating the expressions of SREBP1, FAS and LEPTIN. Levels of hepatic triglyceride, total cholesterol, low density lipoprotein were also reduced by probiotic. Histological analysis showed probiotic alleviated liver steatosis and injury induced by HFD. P. pentosaceus PR-1 might be useful as a dietary health supplement, especially for reducing obesity.

Fermented jellyfish (Rhopilema esculentum) collagen enhances antioxidant activity and cartilage protection on surgically induced osteoarthritis in obese rats.

Collagen has been considered a key treatment option in preventing damage to the articular cartilage over time and supporting the healing process, following the onset of osteoarthritis (OA). This study aimed to investigate the effect of collagen fermented from jellyfish (FJC) by Bacillus subtilis natto on anterior cruciate ligament transection with medial meniscectomy (ACLT + MMx)-induced knee OA in high-fat diet (HFD)-induced obesity in rats. The male Sprague-Dawley rats were fed an HFD for 6weeks before ACLT + MMx surgery, after which they were administered a daily oral gavage of saline (control, OA, and OBOA), either with FJC (20mg/kg, 40mg/kg, and 100mg/kg body weight) or glucosamine sulfate as a positive control (GS; 200mg/kg body weight) for 6weeks. Treatment with FJC decreased the fat weight, triglyceride, and total cholesterol levels in obese rats. Additionally, FJC downregulated the expression of some proinflammatory cytokines, including tumor necrosis factor-α, cyclooxygenase-2, and nitric oxide; suppressed leptin and adiponectin expression; and attenuated cartilage degradation. It also decreased the activities of matrix metalloproteinase (MMP)-1 and MMP-3. These results demonstrated that FJC showed a protective effect on articular cartilage and also suppressed the degradation of cartilage in an animal OA model, suggesting its potential efficacy as a promising candidate for OA treatment.

Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model.

Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface. To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites. BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α, Scf, and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua in vitro. While hypoxic conditions in vitro did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR. In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.

Leptin plays a role in the multiplication of and inflammation in ovarian granulosa cells in polycystic ovary syndrome through the JAK1/STAT3 pathway

ObjectivesThe authors determined the level of Expression of Leptin (LEP) in Polycystic Ovary Syndrome (PCOS) patients with or without obesity and in GCs treated with insulin. MethodsLEP expression was first assessed in ovary cortex specimens collected from women with PCOS with or without obesity as well as from healthy controls. Ovarian Granulosa Cells (OGCs) induced by insulin extracted from a mouse model were used in further functional research. ResultsReal-time PCR and western blotting indicated that LEP expression was upregulated in GCs induced by insulin, in comparison with that in GCs not induced by insulin. Furthermore, the knockdown of LEP resulted in a reduction in growth and multiplication and an increase in apoptosis and inflammation in GCs induced by insulin. Next, the authors evaluated the effect of LEP on three key pathways of inflammation (MAPK, NF-kB, and JAK1/STAT3); results showed that the JAK1/STAT3 pathway was induced by LEP knockdown, as evidenced by the upregulation of phosphor-JAK1, phosphor-STAT3, and nuclear STAT3 expression. Administration of curcumin, a specific inhibitor of STAT3, counteracted the effect of LEP knockdown on cell inflammation and apoptosis. ConclusionThe present data suggest that upregulation of LEP expression in the PCOS granulosa cell model is essential for reducing apoptosis and inflammation by modulating the JAK1/STAT3 pathway axis.

Nine kinds of novel cytokines identified in children with lead exposure

Lead (Pb) is a neurotoxic heavy metal element with many recognized adverse health side effects, and its main target of lead toxicity is the central nervous system. The mechanism of lead toxicity is still uncertain. However, there are few studies investigated the cytokines changes caused by lead exposure in children. The BLLs was quantified using flame atomic absorption spectroscopy. The novel cytokines were detected by RayBio@ Human Cytokine Antibody Array. A total of 4 children with elevated blood lead levels (BLLs) and 4 children with low BLLs were chosen in the study. Volcano plot analysis was performed to identify significant proteins, with the criteria: P value &lt;0.05 and log2 fold change &gt;1. The mean BLLs of children with elevated BLLs (5.675±1.018 μg/dL) has significant difference compared with those with low BLLs (1.975±0.3966 μg/dL) (P=0.0148, t=3.385). And 9 kinds of novel cytokines were identified. The expression of IL-6, IL-8 and IL-17 was significantly up-regulated, while the expression of BDNF, BMP-4, IGF-1, IL-7, IL-10 and Leptin was significantly down-regulated.

Correlations of Omentin-1 and Leptin with Bone Metabolism and Plasma Glucose Upon Type 2 Diabetes Mellitus and Osteoporosis.

The goal was to investigate the correlations of peripheral blood Omentin-1 and leptin (LEP) levels with bone metabolism and plasma glucose in patients with type 2 diabetes mellitus (T2DM) complicated with oste-oporosis (OP). One hundred patients with T2DM admitted from September 2019 to September 2021 were divided into group A (n = 36, OP with T-score ≤ -2.5), group B (n = 50, osteopenia with T-score between -1 and -2.5), and group C (n = 14, non-OP with T-score > -1) according to the values of bone mineral density (BMD). Thirty healthy adults physically examined in the same period were selected as group D. The levels of peripheral blood Omentin-1 and LEP, bone metabolism, and plasma glucose were compared among the four groups. The correlations of peripheral blood Omentin-1 and LEP levels with bone metabolism and plasma glucose were explored by Pearson's analysis. In group A, the levels of Omentin-1 and LEP in peripheral blood were lowest, the serum levels of beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) and osteocalcin (OCN) were highest, the serum level of total N-terminal propeptide of type I procollagen (tPINP) was lowest, and the levels of fasting plasma glucose (FPG), 2-hours postprandial plasma glucose (2hPG) and glycosylated hemoglobin A1c (HbA1c) were highest, se-quentially followed by those of group B, group C, and group D (p < 0.05). Omentin-1 and LEP in peripheral blood were negatively correlated with β-CTX, OCN, 2hPG, and HbA1c and positively correlated with tPINP and FPG (p < 0.05). The expressions of Omentin-1 and LEP in peripheral blood have correlations with bone metabolism and plasma glucose in patients with T2DM complicated with OP.

Correlation between LRG1 and Adipokines in Psoriasis

Background and Objective. Patients with psoriasis may exhibit abnormal changes in serum adipokine levels, which are often related to disease severity of the disease. Leucine‐rich alpha‐2‐glycoprotein 1 (LRG1) is an acute‐phase inflammatory protein that may be linked to adipokines in psoriasis. In this study, we evaluated the differences in the expression of adipokines and LRG1 between patients with psoriasis and healthy individuals, analyzed the correlation between the expression of LRG1 and adipokines, and explored their relationship with psoriatic lesions. Methods. In this cross‐sectional study, patients with psoriasis (n = 54) and healthy controls (n = 26) were enrolled, and their clinical characteristics were recorded. Fasting venous blood samples were collected from each participant. The serum concentrations of leptin, resistin, adiponectin, and LRG1 in each sample were measured using the enzyme‐linked immunosorbent assay. Results. The study included 54 patients with psoriasis vulgaris and 26 healthy controls. The serum levels of LRG1, leptin, and resistin were significantly higher in patients with psoriasis than in healthy controls. Conversely, adiponectin levels were significantly lower in patients with psoriasis. The study showed that LRG1 expression was positively correlated with leptin and resistin expression but negatively correlated with adiponectin expression. Interestingly, only leptin, resistin, and LRG1 expression showed a linear correlation with the Psoriasis Area and Severity Index (PASI). When we categorized patients with psoriasis based on their LRG1 levels, we observed that the group with high LRG1 levels showed a higher PASI. Conclusions. We observed a significant correlation between LRG1 and adipokine expression in patients with psoriasis. In addition, the expression levels of LRG1, leptin, and resistin were observed to be correlated with the severity of psoriasis. We believe that the occurrence and development of psoriasis are collectively influenced by LRG1 and leptin/resistin expression.

The Effect of Supplementation with β-Hydroxy-β-Methylbutyric Acid (HMB) to Pregnant Sows on the Mucosal Structure, Immunolocalization of Intestinal Barrier Proteins, VIP and Leptin in the Large Intestine in their Offspring

Abstract The large intestine epithelium plays an important role in water absorption and participates in fluid, acid-base and electrolyte balance, and the removal of waste products. The large intestine is rich in microorganism-presented enzyme activity. Apart from energy supply, the colon also participates in the synthesis of trophic factors and the modulation of the immune system and the systemic inflammatory response. The current study investigated the effects of dietary HMB administration to pregnant sows on the postnatal development of the colon in their offspring, at weaning. From the 70th to the 90th day of gestation, sows received either a basal diet (n = 12) or the basal diet supplemented with HMB (n = 12) at a dose of 0.2 g/kg of body weight/day. Maternal HMB treatment increased serum IgG and glucose concentrations and decreased serum urea concentration in the piglets. Basal histomorphometric analysis of offspring large intestines showed that prenatal HMB treatment led to a reduction in the thickness of the mucosa, submucosa and both types of myenterons, as well as reduced crypt thickness. The immunoreaction performed to mark T0 lymphocytes and total T lymphocytes in the colon wall showed that prenatal HMB treatment decreased the number of both types of lymphocytes. Greater expression for cadherin was found in the colon of piglets delivered by the HMB-treated sows. The expression of both tight junction proteins (occludin and claudin-3), as well as that of leptin, was stronger in the HMB-treated group. Vasoactive intestinal peptide (VIP) expression was stronger in the submucosal plexuses in the HMB maternal treated piglets, while no changes were observed in the myenteric plexuses. The results obtained indicate that the administration of HMB to pregnant sows significantly influenced the expression of leptin, VIP and some proteins of the intestinal barrier in their offspring, with less influence on large intestine basal morphology.