LEP inhibits intramuscular adipogenesis through the AMPK signaling pathway in vitro.

Leptin can indirectly regulate fatty-acid metabolism and synthesis in muscle in vivo and directly in incubated muscle ex vivo. In addition, non-synonymous mutations in the bovine leptin gene (LEP) are associated with carcass intramuscular fat (IMF) content. However, the effects of LEP on lipid synthesis of adipocytes have not been clearly studied at the cellular level. Therefore, this study focused on bovine primary intramuscular preadipocytes to investigate the effects of LEP on the proliferation and differentiation of intramuscular preadipocytes, as well as its regulatory mechanism in lipid synthesis. The results showed that both the LEP and leptin receptor gene (LEPR) were highly expressed in IMF tissues, and their mRNA expression levels were positively correlated at different developmental stages of intramuscular preadipocytes. The overexpression of LEP inhibited the proliferation and differentiation of intramuscular preadipocytes, while interference with LEP had the opposite effect. Additionally, LEP significantly promoted the phosphorylation level of AMPKα by promoting the protein expression of CAMKK2. Meanwhile, rescue experiments showed that the increasing effect of AMPK inhibitors on the number of intramuscular preadipocytes was significantly weakened by the overexpression of LEP. Furthermore, the overexpression of LEP could weaken the promoting effect of AMPK inhibitor on triglyceride content and droplet accumulation, and prevent the upregulation of adipogenic protein expression (SREBF1, FABP4, FASN, and ACCα) caused by AMPK inhibitor. Taken together, LEP acted on the AMPK signaling pathway by regulating the protein expression of CAMKK2, thereby downregulating the expression of proliferation-related and adipogenic-related genes and proteins, ultimately reducing intramuscular adipogenesis.

Loss of the tumour suppressor LKB1/STK11 uncovers a leptin-mediated sensitivity mechanism to mitochondrial uncouplers for targeted cancer therapy.

Non-small cell lung cancer (NSCLC) constitutes one of the deadliest and most common malignancies. The LKB1/STK11 tumour suppressor is mutated in ∼ 30% of NSCLCs, typically lung adenocarcinomas (LUAD). We implemented zebrafish and human lung organoids as synergistic platforms to pre-clinically screen for metabolic compounds selectively targeting LKB1-deficient tumours. Interestingly, two kinase inhibitors, Piceatannol and Tyrphostin 23, appeared to exert synthetic lethality with LKB1 mutations. Although LKB1 loss alone accelerates energy expenditure, unexpectedly we find that it additionally alters regulation of the key energy homeostasis maintenance player leptin (LEP), further increasing the energetic burden and exposing a vulnerable point; acquired sensitivity to the identified compounds. We show that compound treatment stabilises Hypoxia-inducible factor 1-alpha (HIF1A) by antagonising Von Hippel-Lindau (VHL)-mediated HIF1A ubiquitination, driving LEP hyperactivation. Importantly, we demonstrate that sensitivity to piceatannol/tyrphostin 23 epistatically relies on a HIF1A-LEP-Uncoupling Protein 2 (UCP2) signaling axis lowering cellular energy beyond survival, in already challenged LKB1-deficient cells. Thus, we uncover a pivotal metabolic vulnerability of LKB1-deficient tumours, which may be therapeutically exploited using our identified compounds as mitochondrial uncouplers.

Assessing Mental Health Treatment Receipt Among Asian Adults with Limited English Proficiency Using an Intersectional Approach.

U.S. Asian adults and people with limited English proficiency (LEP) confront mental health treatment receipt disparities. At the intersection of racial and language injustice, Asian adults with LEP may face even greater disparity, but studies have not assessed this through explicitly intersectional approaches. Using 2019 and 2020 National Survey of Drug Use and Health data, we computed disparities in mental health treatment among those with mental illness comparing: Non-Hispanic (NH) Asian adults with LEP to NH White adults without LEP (joint disparity), NH Asian adults without LEP to NH White adults without LEP (referent race disparity), NH Asian adults with LEP to those without LEP (referent LEP disparity), and the joint disparity versus the sum of referent disparities (excess intersectional disparity). In age- and gender-adjusted analyses, excess intersectional disparity was 26.8% (95% CI=-29.8%-83.4%) of the joint disparity in 2019 and 63.0% (95% CI=29.1%-96.8%) in 2020. The 2019 joint disparity was 1.37 (95% CI=0.31-2.42) times that if the race-related disparity did not vary by LEP, and if LEP-related disparity did not vary by race; this figure was 2.70 (95% CI=0.23-5.17) in 2020. These findings highlight the necessity of considering the intersection of race and LEP in addressing mental health treatment disparities.

The serine protease 2 gene regulates lipid metabolism through the LEP/ampkα1/SREBP1 pathway in bovine mammary epithelial cells.

Molecular breeding has brought about significant transformations in the milk market and production system during the twenty-first century. The primary economic characteristic of dairy production pertains to milk fat content. Our previous transcriptome analyses revealed that serine protease 2 (PRSS2) is a candidate gene that could impact milk fat synthesis in bovine mammary epithelial cells (BMECs) of Chinese Holstein dairy cows. To elucidate the function of the PRSS2 gene in milk fat synthesis, we constructed vectors for PRSS2 overexpression and interference and assessed intracellular triglycerides (TGs), cholesterol (CHOL), and nonesterified fatty acid (NEFA) contents in BMECs. Fatty acid varieties and components were also quantified using gas chromatography‒mass spectrometry (GC‒MS) technology. The regulatory pathway mediated by PRSS2 was validated through qPCR, ELISA, and WB techniques. Based on our research findings, PRSS2 emerges as a pivotal gene that regulates the expression of associated genes, thereby making a substantial contribution to lipid metabolism via the leptin (LEP)/Adenylate-activated protein kinase, alpha 1 catalytic subunit (AMPKα1)/sterol regulatory element binding protein 1(SREBP1) pathway by inhibiting TGs and CHOL accumulation while potentially promoting NEFA synthesis in BMECs. Furthermore, the PRSS2 gene enhances intracellular medium- and long-chain fatty acid metabolism by modulating genes related to the LEP/AMPKα1/SREBP1 pathway, leading to increased contents of unsaturated fatty acids C17:1N7 and C22:4N6. This study provides a robust theoretical framework for further investigation into the underlying molecular mechanisms through which PRSS2 influences lipid metabolism in dairy cows.

History and Perspectives of Hyperradical, Laterally Extended Parametrectomy (LEP).

Cervical cancer has been and still is a major global health problem and a major treatment challenge for which surgical interventions have played a key role throughout the past century. In early stages (I/A2-II/B), where high-risk factors are not present, the efficacy of surgical and radiotherapy treatment has been considered equivalent with different (treatment modality specific) complications and quality of life consequences. Negative prognostic factors in early stages of the disease (pelvic lymph-node positivity) and in more advanced stages (parametrial and/or surgical margins' tumor involvement) forecast the deterioration of outlooks for good life expectancy. In these high-risk cases, when radio- or chemoradiotherapy is contraindicated, we investigated the potential role of a more radical surgical approach than the traditional radical hysterectomy. Twenty-five years ago, a hyperradical surgical procedure for the treatment of high-risk cervical cancer patients was introduced in Budapest. The procedure was named as laterally extended parametrectomy (LEP) in Budapest Hungary. The surgical intention was the complete removal of the fibro-fatty tissue content of the pelvis, which contains the lymphatic vessels, lymph nodes, and tumor-affected pelvic side wall structures. We initiated observational studies on the primary treatment in parametrium and/or lymph-node tumor-positive early-stage cases and on second-line surgical therapy of pelvic side wall recurrent tumors following radiotherapy. Promising results of our observational studies propose that prospective randomized trials are worth to be initiated to clarify the potential of this treatment modality in this poor prognosis cohort of patients.

A systematic review and narrative synthesis of health literacy interventions among Spanish speaking populations in the United States.

BACKGROUND: While many populations struggle with health literacy, those who speak Spanish preferentially or exclusively, including Hispanic, immigrant, or migrant populations, may face particular barriers, as they navigate a predominantly English-language healthcare system. This population also faces greater morbidity and mortality from treatable chronic diseases, such as hypertension and diabetes. The aim of this systematic review was to describe existing health literacy interventions for patients with a Spanish-language preference and present their effectiveness. METHODS: We carried out a systematic review where Web of Science, EMBASE, and PubMed were queried using MeSH terms to identify relevant literature. Included articles described patients with a Spanish-language preference participating in interventions to improve health literacy levels in the United States. Screening and data abstraction were conducted independently and in pairs. Risk of bias assessments were conducted using validated appraisal tools. RESULTS: A total of 2823 studies were identified, of which 62 met our eligibility criteria. The studies took place in a variety of community and clinical settings and used varied tools for measuring health literacy. Of the interventions, 28 consisted of in-person education and 27 implemented multimedia education, with 89% of studies in each category finding significant results. The remaining seven studies featured multimodal interventions, all of which achieved significant results. CONCLUSION: Successful strategies included the addition of liaison roles, such as promotores (Hispanic community health workers), and the use of multimedia fotonovelas (photo comics) with linguistic and cultural adaptations. In some cases, the external validity of the results was limited. Improving low health literacy in patients with a Spanish-language preference, a population with existing barriers to high quality of care, may help them better navigate health infrastructure and make informed decisions regarding their health. REGISTRATION: PROSPERO (available at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257655.t ).

Improving pain communication between limited English-speaking Hmong patients, medical interpreters, and health care providers in primary care: A pilot study.

This pilot study assessed the feasibility of implementing a pain assessment information visualization (InfoViz) tool to address cultural and language barriers among limited English proficiency (LEP) Hmong patients in primary care. We used a static group comparison design to collect data from 20 patient, interpreter, and provider triads under usual care (i.e., interpreter using verbal pain descriptions), followed by another 20 triads under the intervention (i.e., interpreter using verbal pain descriptions and the InfoViz tool). Feasibility outcomes included recruitment and retention rates, InfoViz tool completion, acceptability, and fidelity. We also assessed mutual understanding (MU) and pain electronic health record (EHR) documentation. Descriptive data were calculated and thematic analysis was conducted. Thirty-six LEP Hmong patients (n = 29 female, mean age = 59.03), 27 providers (n = 15 female), and four interpreters participated in this study. The patient recruitment rate was 18% while the retention rate was 81%. Interpreter recruitment rate was 80%, and 75% for retention rate. The intervention fidelity mean score was 83%. In the intervention condition, patient-provider MU of pain severity improved by 30%, coupled with a 28% increase in pain severity EHR documentation compared to usual care. While communication of pain quality did not improve, there was a higher mean number of pain descriptors (3.31 in the intervention vs. 1.79 in usual care) in EHR documentation. All participants had a positive experience with the tool, reporting it as valuable with 100% completeness of all tools. Findings revealed the tool was acceptable and feasible to use among LEP patients-interpreters-providers, providing support for an efficacy study.

Biopsychosocial factors associated with pain management in older adults with limited English proficiency.

Chronic pain is a prevalent issue among older adults, and effective communication plays a crucial role in accurately conveying the nature of their pain. However, older immigrant adults with limited English proficiency (LEP) encounter significant challenges in expressing the severity and type of pain they experience, creating additional obstacles in their interactions with healthcare providers. This study explored the experience of managing pain among 26 Farsi-speaking older adults with chronic pain. Semi-structured interviews were conducted and data were analyzed using grounded theory methodology. Using the biopsychosocial framework, three main categories of psychological, social, and biological factors arose from data. Depression, stress, sleep disturbances, lack of social support, health literacy, and misdiagnosis or underdiagnosis affected managing pain among older immigrants with LEP. Providing culturally and linguistically competent healthcare providers, particularly in states with a higher number of LEP immigrants, will help maximize the quality of care for patients with chronic pain.

Congenital leptin and leptin receptor deficiencies in nine new families: identification of six novel variants and review of literature.

Early childhood obesity is a real public health problem worldwide. Identifying the etiologies, especially treatable and preventable causes, can direct health professionals toward proper management. Measurement of serum leptin levels is helpful in the diagnosis of congenital leptin and leptin receptor deficiencies which are considered important rare causes of early childhood obesity. The main aim of this study was to investigate the frequency of LEP, LEPR, and MC4R gene variants among a cohort of Egyptian patients with severe early onset obesity. The current cross-sectional study included 30 children who developed obesity during the first year of life with BMI > 2SD (for age and sex). The studied patients were subjected to full medical history taking, anthropometric measurements, serum leptin and insulin assays, and genetic testing of LEP, LEPR and MC4R. Disease causing variants in LEP and LEPR were identified in 10/30 patients with a detection rate of 30%. Eight different homozygous variants (two pathogenic, three likely pathogenic, and three variants of uncertain significant) were identified in the two genes, including six previously unreported LEPR variants. Of them, a new frameshift variant in LEPR gene (c.1045delT, p.S349Lfs*22) was recurrent in two unrelated families and seems to have a founder effect in our population. In conclusion, we reported ten new patients with leptin and leptin receptor deficiencies and identified six novel LEPR variants expanding the mutational spectrum of this rare disorder. Furthermore, the diagnosis of these patients helped us in genetic counseling and patients' managements specially with the availability of drugs for LEP and LEPR deficiencies.

GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population.

Objective. Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population. Methods. The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL, LEP, and LEPR genes polymorphism (rs696217, rs7799039, rs1137100, rs1137101, rs1805094) was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones (leptin, ghrelin, adiponectin, resistin) were determined with commercially available kits using a Multiskan FC analyzer. Results. The study of the effect of genotypes of the GHRL (rs696217), LEP (rs7799039), and LEPR (rs1137100, rs1805094) polymorphisms on the level of metabolic hormones (leptin, ghrelin, adiponectin, resistin) in the blood of obese patients did not show reliably significant results. Thus, the presence of the LEPR genes (rs1137101) polymorphism in the Ukrainian population indicates an increased risk of the metabolic syndrome development regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG). Conclusions. We established a significant effect of the presence of the A allele and G allele of the LEPR gene polymorphism (rs1137101) on the level of leptin, ghrelin, adiponectin, and resistin in the serum of patients diagnosed with the metabolic syndrome in the Ukrainian population.

Genetic Association of LEP Gene Polymorphisms with Obesity in Moroccan Individuals: Case-Control Study and Updated Meta-analysis.

Obesity is a global epidemic disease representing the fifth leading cause of death in the world. It was shown that it is caused by the interaction between environmental factors and genes including leptin gene (LEP). This paper aimed to analyze the association between the LEP gene polymorphisms rs7799039 and rs11761556 with obesity in Moroccan individuals as well as to perform an update meta-analysis of this genetic association. Both polymorphisms were genotyped in 146 obesity patients and 104 controls using real-time PCR technique. The genetic association analysis and the comparison of quantitative parameters were carried out using the R language. Moreover, a meta-analysis including 20 genetic association studies was performed using Review Manager 5.3 software. No significant association was found between the polymorphisms rs7799039 and rs11761556 and the risk of obesity. The comparison of biochemical and clinical parameters between the genotypes of the rs7799039 polymorphism, showed a significant increased triglycerides levels in carriers of AA or GA genotypes (P value = 0.040). The meta-analysis showed no significant association between the rs7799039 polymorphism and obesity under all genetic models. In conclusion, the case-control study and meta-analysis demonstrated that the LEP gene polymorphisms rs7799039 and rs11761556 cannot be considered as genetic risk factors for obesity.

Spanish for Veterinarians Part 2: A Survey Gauging Student Perspectives on a Profession-Specific Language Learning Experience.

This article describes the distribution and results of a survey that was disseminated among students enrolled in Doctor of Veterinary Medicine (DVM) programs in the United States. It is a critical component to a substantial effort being undertaken at Colorado State University (CSU) to overhaul their current Spanish for Veterinarians offerings (outlined and discussed in Spanish for Veterinarians Part 1: An Approach to Weaving Spanish Language Education into DVM Curricula) into a cohesive Spanish language program that offers consistent synchronous exposure to the language and guided practice over several semesters of instruction. The information obtained in this survey informs on veterinary student interest in and availability to engage in Spanish coursework created specifically for the veterinary field, as well as students' previous Spanish language learning experience. Additionally, it investigates the reasons motivating students' desire to participate in a Spanish for Veterinarians program, and their expectations and perspectives about receiving credit and paying for enrollment. It also includes students' online learning preferences and overall suggestions for optimal engagement in a Spanish language learning experience offered during DVM School. The anonymous results indicated that most respondents had taken Spanish only in high school, followed by those with one or two college-level courses. Interest in learning Spanish for the veterinary field is high and most students are willing to dedicate 2 to 4 hours weekly to language learning. This information guides curricular design decisions for a new Spanish for Veterinarians program that is currently being developed at CSU.

Spanish for Veterinarians Part 1: An Approach to Weaving Spanish Language Education into DVM Curricula.

The authors describe the need for discipline-specific Spanish language training in veterinary programs and elaborate on student interest in veterinary Spanish offerings. They outline their interdisciplinary approach to field-specific Spanish curriculum development that evolved from a single third-year practicum offering into a 7-credit Spanish language program while summarizing curriculum content, assessments, and student feedback. The challenges and approaches to weaving the language program into a demanding veterinary curriculum are addressed and program limitations are discussed. The paper ends with an outline of exciting future directions currently underway that hold achieving the necessary level of Spanish language proficiency for successful communication about animal health and wellbeing as a primary goal. The intent of this publication is to shed light on unique aspects associated with designing and delivering a Spanish language program within veterinary education, including the importance of interdisciplinary collaboration with language teaching professionals for curriculum development and delivery.

Deleted genes associated with obesity in Mexican patients diagnosed with nonalcoholic fatty liver disease.

AIM: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic condition in which both lifestyle and genetic factors have a pathogenic role. The LEP gene encodes leptin, which regulates appetite, body weight, and several metabolic functions. Proopiomelanocortin (POMC), regulates food intake and energy balance. The aim of the study was to determine partial or complete deletions of genes associated with obesity in patients diagnosed with NAFLD. MATERIAL AND METHODS: Blood samples and DNA from 43 individuals diagnosed with NAFLD by ultrasonographic technique (Fibroscan) were obtained. The partial or complete deletions of genes were determined by MLPA (Multiplex Ligation-dependent Probe Amplification) using the SALSA probemix P220-B2 Obesity only on 43 individuals. Fifty blood samples from healthy individuals were included. RESULTS: Eleven out of 43 individuals analyzed by MLPA presented some deletion of the genes analyzed: six were female and five were male. The partial or complete deletion of the LEPR and POMC genes was observed in eight patients (18.6%), SIM1 in six patients (13.9%), GRIK2 and SH2B1 in two patients (4.7%), SEZGL2 in four patients (9.3%), and MCR4 in one patient (2.3%). CONCLUSION: Partial deletion was observed in LEPR, POMC, SIM1, GRIK2, SH2B1, SEZGL2, and MCR4 genes in 26% of the cases, and we suggest that these alterations probably has a potential relationship for the development of NAFLD.

An accessible, relational, inclusive, and actionable (ARIA) model of genetic counseling compared with usual care: Results of a randomized controlled trial.

PURPOSE: Effective approaches to communicate genomic information are needed to ensure equitable care. In a randomized controlled superiority trial, we tested a novel practice model that aims to make genetic counseling inclusive, by making the communication accessible, relational, and actionable (ARIA). METHODS: In total, 696 English- and Spanish-speaking patients aged 18 to 49 years, enriched for individuals from historically underserved backgrounds, were randomized in 1:1 ratio to ARIA or usual care. Primary outcomes were accuracy of recall, communication satisfaction, and perceived understanding. In total, 33 participants completed qualitative interviews. RESULTS: Recall and understanding were high for all participants. ARIA participants scored higher on the relationship scale of communication satisfaction (mean difference = 0.09, 95% CI = <0.01 to 0.17). Moderator analyses of communication satisfaction showed that those with lower health literacy reported less communication difficulty in ARIA and those using medical interpreters reported greater communication ease in ARIA. No significant difference was found on other primary and secondary outcomes. Qualitative data enhanced understanding of how and why ARIA can be effective. CONCLUSION: This study provides evidence that a genetic counseling intervention that focuses on specific communication skills to enhance relationship-building, patient engagement, and comprehension can be effective with all patients and may be especially valuable for patients of lower health literacy and Spanish-speakers who use a medical interpreter.

Preventive care use among Hispanic adults with limited comfort speaking English: An analysis of the Medical Expenditure Panel Survey data.

Language barriers have been associated with worse access to healthcare and poorer health outcomes. To assess differences in access to care and utilization of healthcare services between Hispanic adults and non-Hispanic white adults (NHW), we used the Medical Expenditure Panel Survey (2013-2016) to compare Hispanic adults who expressed limited comfort speaking in English (LCE) with Hispanic adults who were comfortable speaking in English (CE) and NHW adults. Hispanic adults with CE were less likely than NHW adults to have a usual source of care, use preventive services, including cervical cancer screening, and healthcare services. However, after adjustment breast and cervical cancer screening exceeded that of NHW adults. Hispanic adults with LCE fared substantially worse than their Hispanic counterparts with CE in having a usual source of care, use of preventive services, breast and colorectal cancer screening, and healthcare services. After adjustment, use of all cancer screening tests were similar. Eliminating disparities for Hispanic adults will require a multi-pronged approach to address access to healthcare and other social determinants of health, including poverty, employment discrimination, and educational inequities. The public health community can help improve health literacy, address barriers to care, and provide appropriate language assistance at point of care using culturally-competent means to promote greater utilization of preventive services, including demand for and delivery of cancer screenings.

Association of LEPR polymorphisms with egg production and growth performance in female Japanese quails.

This study aimed to screen intron 8 of the leptin receptor (LEPR) gene for polymorphisms in female Japanese quails. Two adjacent novel SNPs (A277G and A304G) were detected using PCR-SSCP and sequencing. These SNPs produced three haplotypes (AA/AA, AG/AG, and GG/GG) that were significantly (p ≤ 0.05) associated with growth and egg production traits. GG/GG haplotype-quails had significantly (p ≤ 0.05) lower egg production, feed intake, growth performance, lipid profile, serum levels of sex hormones (estradiol, progesterone, FSH, LH), and ovarian expressions of survivin, FSHR, and IGF1 than other quails. However, GG/GG quails had significantly (p ≤ 0.05) higher serum levels of LEP and mRNA levels of LEPR, LEP, and caspase 3 in the hypothalamus and ovaries. These higher levels of LEP/LEPR could not only reduce feed intake and body weight gain but also could induce apoptosis of ovarian cells (as indicated by lower survivin and IGF1 and higher caspase3 expression) which could inhibit the development of the follicles and the release of sex hormones with a subsequent decrease in egg production in GG/GG quails. Therefore, with these results, we suggest selecting Japanese quails with AA/AA and AG/AG haplotypes to improve the reproduction and growth performance of this flock.

Leptin Signaling in Obesity and Colorectal Cancer.

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin's relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.

Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD), for which obesity and genetics are known risk factors, is a chronic process that alters the structure and function of the intervertebral discs (IVD). Circulating leptin is positively correlated with body weight and is often measured to elucidate the pathogenesis of IVD degeneration. In this study, we examined the associations of LEP single nucleotide polymorphisms (SNPs) genetic and environmental effects with IVDD. A total of 303 Taiwanese patients with IVDD (mean age, 58.6 ± 12.7 years) undergoing cervical discectomy for neck pain or lumbar discectomy for back pain were enrolled. Commercially available enzyme-linked immunosorbent assay (ELISA) kits measured the circulating plasma leptin levels. TaqMan SNP genotyping assays genotyped the LEP SNPs rs2167270 and rs7799039. Leptin levels were significantly increased in obese individuals (p < 0.001) and non-obese or obese women (p < 0.001). In the dominant model, recoded minor alleles of rs2167270 and rs7799039 were associated with higher leptin levels in all individuals (p = 0.011, p = 0.012). Further, the association between these LEP SNPs and leptin levels was significant only in obese women (p = 0.025 and p = 0.008, respectively). There was an interaction effect between sex and obesity, particularly among obese women (interaction p = 0.04 and 0.02, respectively). Our findings demonstrate that these SNPs have sex-specific associations with BMI in IVDD patients, and that obesity and sex, particularly among obese women, may modify the LEP transcription effect.

Association of PRLR, IGF1, and LEP genes polymorphism with milk production and litter size in Egyptian Zaraibi goat.

Studying variation in genes responsible for physiological characters is important to enhance goat productive and reproductive efficiency. This study aimed to detect specific nucleotide polymorphisms in prolactin receptor (PRLR), insulin-like growth factor (IGF1), and leptin (LEP) genes and their correlation with milk production (MP) and litter size (LS) traits in Zaraibi goat. PCR-SSCP products of different patterns of each gene were sequenced and aligned to reveal two mutations (T > C) and (G > A) in 3'UTR of PRLR gene and registered on NCBI with accession numbers OM418863 for TT and OM418864 for CT, while (G > A) variation was registered as OM418861 for GG and OM418862 for AG in exon 10. TT, CT, AG, and GG genotypes were distributed in the studied animals with frequencies 0.43, 0.57, 0.65, and 0.35, respectively. While alleles C, T, A, and G frequencies were 0.28, 0.72, 0.32, and 0.68, respectively. CT and AG genotypes associated significantly (P < 0.05) with higher MP and LS, respectively. By studying the haplotypes of PRLR, C-A and T-A were associated with the highest and the lowest level of MP, respectively. For LS, T-A and C-G showed significant correlation with the highest and the lowest rate, respectively. Regarding IGF1 gene, two polymorphisms were detected; T74C at exon 4 which registered on NCBI as OM418860, and combined mutations as ins. G470, A531G, and T534C (PP genotype) at 5' flanking region that registered as OM418859. For LEP, only one polymorphism was found in intron 2 (G281A) which submitted to NCBI as OM418855. All detected polymorphisms have shown to be involved in regulating the MP or LS as reproductive traits in goat.