Search Results (405)

The increasing demand for food to meet the needs of the planet’s growing population requires, among other factors, greater and improved meat production. Meat quality is determined by key consumer-preferred traits, particularly tenderness, juiciness, and flavor. Recently, interest has grown in analyzing the genes associated with these phenotypic characteristics. Single-nucleotide polymorphisms (SNPs) are common genomic variations in cattle and represent the most widely used molecular markers. Research on SNP variation is now a major focus of genomic studies aimed at improving meat quality. Leptin levels reflect the amount of adipose tissue in meat, also known as marbling. Several SNPs in the leptin gene and its receptor have been linked to this meat quality trait. Similarly, SNPs in the calpain/calpastatin system play a significant role in postmortem muscle proteolysis and pork tenderness. This review examines these genetic variants as markers involved in the expression of phenotypic traits in meat products and explores their mechanisms of action. Additionally, it provides insights into the genetic variants associated with production-related characteristics. Full article

Xylosyltransferase-I (XT-I) plays a crucial role in skeletal development and cartilage integrity. An XT-I deficiency is linked to severe bone disorders, such as Desbuquois dysplasia type 2. While animal models have provided insights into XT-I’s role during skeletal development, its specific effects on adult bone homeostasis, particularly in human mesenchymal stem cell (hMSC) differentiation, remain unclear. This study investigates how XT-I deficiency impacts the differentiation of hMSCs into chondrocytes, osteoblasts, and adipocytes—key processes in bone formation and repair. The aim of this study was to elucidate for the first time the molecular mechanisms by which XT-I deficiency leads to impaired bone homeostasis. Using CRISPR-Cas9-mediated gene editing, we generated XYLT1 knockdown (KD) hMSCs to assess their differentiation potential. Our findings revealed significant disruption in the chondrogenic differentiation in KD hMSCs, characterized by the altered expression of regulatory factors and extracellular matrix components, suggesting premature chondrocyte hypertrophy. Despite the presence of perilipin-coated lipid droplets in the adipogenic pathway, the overall leptin mRNA and protein expression was reduced in KD hMSCs, indicating a compromised lipid metabolism. Conversely, osteogenic differentiation was largely unaffected, with KD and wild-type hMSCs exhibiting comparable mineralization processes, indicating that critical aspects of osteogenesis were preserved despite the XYLT1 deficiency. In summary, these results underscore XT-I’s pivotal role in regulating differentiation pathways within the bone marrow niche, influencing cellular functions critical for skeletal health. A deeper insight into bone biology may pave the way for the development of innovative therapeutic approaches to improve bone health and treat skeletal disorders. Full article

Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article

L-carnitine and Mildronate are substances that can significantly rearrange the energy metabolism of cells. This can potentially cause changes in the bacterial composition of the gut microbiome and affect testis functionality and male sexual health. Mice of the C57Bl/6 line were used. Sexual behavior was assessed using physiological tests, and gene expression patterns were assessed by qPCR. High-throughput sequencing of mouse fecal microbiota was performed. We showed that long-term administration of Mildronate has no significant effect on the intestinal microbiome, and there was a compensatory increase in the expression of genes involved in fatty acid and leptin metabolism. No impairment of sexual motivation in male mice was observed. Prolonged L-carnitine supplementation caused a decrease in alpha diversity of bacteria and a decrease in some groups of microorganisms that are components of a healthy gut microflora. A correlation was observed between the level of bacteria from Firmicutes phylum, indicators of sexual motivation of mice, and the dynamics of body weight gain. Our results may indicate that metabolic modulators can have a significant impact on the structure of the bacterial community of the gut microbiome, which may influence male sexual health through the gut–semen axis. Full article

Nero Siciliano (NS) is an autochthonous pig breed reared in northeastern Sicily; despite its high-quality meat products, NS is currently endangered. This study aimed to evaluate the genetic variability at nine loci within candidate genes for meat traits—Melanocortin 4 Receptor (MC4R), Ryanodine Receptor 1 (RYR1), Class 3 Phosphoinositide 3-Kinase (PIK3C3) and Leptin (LEP)—to provide useful information for preservation and exploitation of the NS pig breed. Distribution of the genetic variants was assessed in a representative sample of 87 pigs (18 boars and 69 sows) collected in nine farms located in the original breeding area. Genotypes have been determined using PCR-RFLP and Sanger sequencing. Alleles linked to different growth rates and back fat deposition showed high frequencies (MC4R c.175C—0.93; LEP g.3469T—0.91) in the whole sample. Deviations from Hardy–Weinberg equilibrium and different allele distribution in boars and sows were observed. The RYR1 g.1843T allele, associated with Malignant Hyperthermia and Pale Soft Exudative meat defect, was reported in seven heterozygote pigs (q = 0.04) with one farm exhibiting a frequency of 0.29. Our results suggest the need for continuous monitoring of the genetic variants in NS both to maintain high meat quality and eradicate the RYR1 g.1843T allele. Full article

Leptin-deficient (ob/ob) and leptin receptor (Lepr)-deficient db/db mice develop a mild form of osteoclast-rich osteopetrosis, most evident in long bone epiphyses, implying leptin is important for normal replacement of cartilage during skeletal maturation. However, it is unclear whether leptin acts as a permissive or regulatory factor and whether its actions are mediated via peripheral pathways. Here we show the osteopetrotic phenotype is not evident in ob/+ or db/+ mice, suggesting that leptin acts as a critical but permissive factor for skeletal maturation. The importance of leptin is further supported by our results showing that interventions known to increase bone resorption (mild cold stress, simulated microgravity, or particle-induced inflammation) did not advance skeletal maturation in ob/ob mice whereas long-duration hypothalamic leptin gene therapy was effective. Additionally, administration of leptin by subcutaneously implanted osmotic pumps (400 ng/h) for 2 weeks accelerated skeletal maturation in ob/ob mice. Because leptin has the potential to act on the skeleton through peripheral pathways, we interrogated osteoclast-lineage cells for the presence of Lepr and evaluated skeletal response to the introduction of bone marrow Lepr⁺ cells into db/db mice. We identified Lepr on marrow MCSFR⁺CD11b⁺ osteoclast precursors and on osteoclasts generated in vitro. We then adoptively transferred Lepr⁺ marrow cells from GFP mice or wildtype (WT) mice into Lepr^- db/db mice. Following engraftment, most MCSFR⁺ CD11b⁺ cells in marrow expressed GFP. Whereas db/db→db/db had minimal influence on epiphyseal cartilage, WT→db/db decreased cartilage. These findings suggest peripheral leptin signaling is required for normal osteoclast-dependent replacement of cartilage by bone during skeletal maturation. Full article

This overview explores the complex relationship between environmental factors, particularly obesity, and the timing of puberty, with a focus on how hormonal and genetic interactions are influenced by external conditions. Puberty (gonadarche) is characterised by the activation of the hypothalamic–pituitary–gonadal (HPG) axis. The onset and progression of puberty vary significantly among individuals, primarily due to genetic factors, with key genes like kisspeptin 1 (KISS1) and makorin ring finger protein 3 (MKRN3) playing a crucial role. Cohesively, this paper emphasises that environmental factors, particularly obesity and exposure to endocrine-disrupting chemicals (EDCs), have become significant influences on the timing of puberty. Childhood obesity has risen significantly in recent decades and the age of pubertal onset has declined over the same period. Obesity greatly disrupts hormone regulation in pre-pubertal children. Leptin accelerates the onset of puberty in girls but not in boys. The underlying mechanism is proposed to be the increase in Kiss1/GnRH signalling. On the contrary, excess leptin in boys suppresses testosterone production by increasing oestrogen conversion. Low adiponectin in obese girls may contribute to earlier puberty due to a reduced inhibition of Kiss1/GnRH signalling. Low adiponectin in boys is linked to delayed puberty due to its role in maintaining insulin sensitivity and testosterone production. Hyperinsulinemia influences pubertal timing through central and peripheral mechanisms. Insulin acting synergistically with leptin promotes the earlier onset of puberty in girls but not in boys. The effects of exposure to certain EDCs—mostly obesogenic chemicals that mimic the action of natural hormones—on the timing of puberty remain unclear; hence, further research on this topic is needed. Addressing and preventing obesity in children could potentially mitigate these alterations in pubertal timing. Full article

This study aimed to identify and analyse the copy number variations (CNVs) in the genes involved in the pathophysiology of obesity and correlate these findings with the phenotypic manifestations. Genetic screening of 59 apparently healthy individuals with elevated adipose tissue percentages was performed, assessing the duplications and deletions of obesity-related genes through the MLPA (Multiplex Ligation-dependent Probe Amplification) technique. Clinical and metabolic parameters, including insulin, HOMA-IR, leptin, and adiponectin levels, were measured to better describe the obesity profiles of the participants in this study. In our research, 11.86% of the subjects presented with genetic alterations in obesity-associated genes, with 16% of these modifications involving concurrent duplications in SEZ6L2-1 and SH2B1-2, linked to doubled insulin and tripled HOMA-IR levels. However, the same duplications were associated with a reduced trunk adipose tissue percentage (but not BMI), suggesting leptin signalling modulation. Duplications were more frequent in the metabolically unhealthy obese patients, resulting in a higher relative risk of an obese metabolically unhealthy diagnosis (1.85-fold increased risk in subjects with SEZ6L2-1/SH2B1-2 duplications, p = 0.52). No duplications or deletions were reported in the non-obese patient groups, defined according to the BMI criteria. A partial LEPR deletion was identified in one patient, associated with severe insulin resistance (second-highest HOMA-IR in the cohort). Another subject presented with 11 duplications (7 in LEPR) and reported the lowest adiponectin and second-highest leptin levels among the genetically altered subjects. The genetic profiles revealed complex associations between the CNVs and obesity phenotypes, highlighting the potential for early risk stratification. Despite the interpretative challenges, identifying the genetic predispositions could significantly predict cardiometabolic risk and be used to map personalised interventions to possibly modulate phenotypic expression. Full article

The differential diagnosis of erosive osteoarthritis of the hand (EHOA) and psoriatic arthritis (PsA) is challenging, especially considering the absence of specific diagnostic biomarkers. The aim of the present study was to evaluate whether a pattern of microRNAs (miRNAs) (miR-21, miR-140, miR-146a, miR-155, miR-181a, miR-223), pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-17a, IL-23a, and tumor necrosis factor (TNF)-α], and adipokines (adiponectin, chemerin, leptin, resistin, and visfatin) could help to differentiate EHOA from PsA. Fifty patients with EHOA, fifty patients with PsA, and fifty healthy subjects (HS) were studied. The gene expression of miRNAs and cytokines were evaluated by real-time PCR from peripheral blood mononuclear cells and serum levels of cytokines and adipokines were quantified by ELISA in PsA and EHOA patients and HS. Gene expression showed the significant up-regulation of the analyzed miRNAs in EHOA and PsA patients as compared to HS and higher miR-155 in EHOA vs. PsA patients. The expression levels of IL-1β and IL-6 did not show any significant differences between EHOA and PsA, while IL-17a and IL-23a were significantly up-regulated in PsA compared to EHOA. Circulating TNF-α levels were higher in EHOA compared to PsA, while PsA patients exhibited significantly elevated levels of IL-23a. The combination of miR-155 with C-reactive protein enhanced the ability to differentiate EHOA from PsA, further supporting the potential of miR-155 as a diagnostic biomarker. Full article

Background: Severe and difficult-to-control asthma occurs in 3–10% of patients in developed countries. The aim of our study was to investigate the association of the prognostic role of leptin and adiponectin, as well as the leptin receptor gene polymorphism Gln223Arg, in patients with difficult-to-control and severe asthma. Methods: The present study included 200 patients with asthma hospitalized in the Department of Pulmonology between January 2018 and December 2021. In all patients, in addition to routine clinical investigations, adiponectin, leptin and their ratio were analyzed, as well as levels of pro-inflammatory cytokines (IL-6, IL-8 and TNF-alpha). External respiratory function was also assessed. LEPR Gln223Arg single-nucleotide polymorphisms were genotyped by real-time PCR method. Results: Patients were randomized into two groups, depending on the severity of asthma: an uncontrolled asthma group and a controlled asthma group, according to the GINA criteria. Among patients with uncontrolled asthma, 101 subjects (74.3%) had metabolic syndrome (p < 0.001). There was an inverse association of the adiponectin/leptin ratio with the eosinophil count (B = −0.305, p < 0.001), IL-6 (B = −0.026, p < 0.001), IL-8 (B = −0.062, p < 0.001) and TNF-alpha (B = −0.047, p < 0.001) and a direct correlation with the level of FEV1 (B = 0.121, p < 0.001) and FVC (B = 0.104, p < 0.001). A probable association of homozygous A/A allele with increased risk of uncontrolled asthma was shown (p = 0.007). Conclusions: Leptin receptor polymorphism with A/A genotype may be associated with a higher probability of developing severe and difficult-to-control asthma. Full article

Traditional Chinese medicine has long acknowledged the therapeutic potential of Tetradium ruticarpum (A.Juss.) T.G.Hartley together with Coptis chinensis Franch in managing metabolic disorders. However, their combined anti-obesity effects and the underlying mechanisms remain poorly characterized. This study investigates the synergistic anti-obesity effects and mechanisms of a combined berberine and evodiamine treatment (BBE) in high-fat diet (HFD)-induced C57BL/6J mice and 3T3-L1 cells. In vitro, cell viability was evaluated using the Cell Counting Kit-8 (CCK-8), while lipid accumulation was assessed through Oil Red O staining and triglyceride content determination. Molecular docking simulations performed with AutoDockTools 1.5.6 software Vina predicted interactions between BBE and key proteins. The analysis of genes and proteins involved in browning and thermogenesis was conducted using quantitative reverse transcription polymerase chain reaction and Western blotting. In vivo, HFD-induced mice were assessed for serum lipids profiles, glucose, insulin, adipocytokines, fat tissue morphology (Hematoxylin and eosin staining), mitochondrial activity (flow cytometry), and protein expression (immunofluorescence). Molecular docking analysis revealed strong binding affinities between BBE and key target proteins, including UCP1, PGC-1α, PRDM16, CIDEA, FGF21, and FGFR1c. BBE significantly reduced lipid accumulation in 3T3-L1 cells, upregulated the mRNA expression of Prdm16, Cidea, Ucp1, and Dio2, elevated UCP1 and PGC-1α protein levels, and activated the FGF21/PGC-1α signaling pathway. In HFD-induced mice, BBE administration led to reduced body weight, smaller adipocyte size, increased adipocyte number, and alleviated hepatic steatosis. Furthermore, it lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and levels of triglycerides (TG), while simultaneously increasing concentrations of high-density lipoprotein cholesterol (HDL-C). BBE also improved glucose tolerance, reduced fasting insulin levels, and modulated adipocytokine levels (reduced leptin, increased adiponectin), while promoting browning gene and protein expression. Overall, the combination of berberine and evodiamine mitigates obesity by enhancing browning and activating the FGF21/PGC-1α signaling pathway. Full article

RNA methylation plays a critical role in regulating all aspects of RNA function, which are implicated in the pathogenesis of various human diseases. Recent studies emphasize the role of 5-methylcytosine (m5C), an RNA modification, in key biological functions. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading chronic liver condition globally. However, the relationship between m5C methylation and MASLD remains unclear. This study aimed to investigate m5C modification in a mouse model of MASLD. In this research, using RNA transcriptome sequencing (RNA-Seq) and methylated RNA bisulfite sequencing (RNA-BS-Seq) in leptin receptor-deficient mice, we found that genes associated with hypermethylation were primarily linked to lipid metabolism. We identified 156 overlapping and differentially expressed genes (DEGs) that changed at both the mRNA expression level and the m5C modification level. Among them, 72 genes showed elevated expression and m5C modification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these genes were significantly associated with lipid metabolism-related signaling pathways. Our results demonstrate that m5C methylation modifications may play an important role in the development of MASLD. Full article

Leptin is an adipokine known as a regulator of feeding and metabolism in mammals. Previous studies on fish have revealed its role in food intake regulation in limited teleosts. However, its specific function in Siberian sturgeon, an ancient Chondrostei fish, remains poorly understood. This study represents the first successful cloning of sequences for leptin and leptin receptors in Siberian sturgeon, achieved using RT-PCR. The predicted leptin sequence in this species consists of 168 amino acids that exhibit low identity with other fish species, except within the Acipenseriformes order. Tissue distribution analysis revealed a high expression of Siberian sturgeon leptin mRNA in the liver and lepr mRNA in the hypothalamus. Fasting differentially affected the expression of leptin and lepr mRNA, with decreased levels in the hypothalamus and increased levels in the liver (leptin: 3–15 days; lepr: 6–15 days). Recombinant Siberian sturgeon leptin (Ssleptin) was produced via E. coli expression, and intraperitoneal injection (100 ng/g BW) significantly inhibited food intake. The anorectic effect was correlated with changes in hypothalamic gene expression, including downregulation of orexigenic factors (agrp, orexin, npy, and ghrelin) and upregulation of anorexigenic factors (pomc, mch, and insulin). Meanwhile, the peripheral administration of Ssleptin promoted the expression of resistin in the liver and concurrently increased cck and pyy mRNA levels in the valvular intestine. Furthermore, Ssleptin injection stimulated the expression of hypothalamic lepr, jak2, akt, and ampkα2 mRNA. These findings suggest that leptin plays a significant role in the feeding control of Siberian sturgeon and provide new insights into the evolutionary function of leptin in fish. Full article

This study examines the relationship between obesity, oxidative stress, and reproductive dysfunction. It focuses on the effects of sleeve gastrectomy on gene expression and hormone profiles in 29 women with severe obesity (BMI ≥ 40 kg/m²). Pre- and post-surgical investigations revealed significant differences in major gene expressions and hormonal markers. CART expression reduced significantly from 0.27 ± 4.43 to −3.42 ± 1.14 (p < 0.001), while leptin expression decreased from −1.87 ± 1.75 to −0.13 ± 1.55 (p < 0.001), indicating better metabolic regulation. In contrast, eNOS expression increased considerably from −4.87 ± 1.70 to 1.18 ± 2.31 (p = 0.003), indicating improved endothelial function and nitric oxide bioavailability, which is critical for vascular health and reproduction. Correlation research before surgery indicated no significant relationships between eNOS, CART, or leptin and clinical indicators, implying that these genes function independently in pre-surgical metabolism. While most associations remained negligible after surgery, a significant negative connection between eNOS expression and SHBG levels appeared (r = −0.365, p = 0.049), indicating potential interactions in hormonal regulation pathways following metabolic improvements. These findings emphasize the importance of bariatric surgery in reducing the negative effects of obesity on reproductive health by altering critical cellular pathways. Significant increases in CART, leptin, and eNOS expression indicate reduced oxidative stress, improved vascular tone, and hormonal balance, all of which contribute to increased reproductive capacity. This study sheds light on the molecular processes that link obesity, metabolic health, and fertility, underlining bariatric surgery’s therapeutic potential for women experiencing obesity-related infertility. Full article

Genetic obesity results from loss-of-function mutations, including those affecting the leptin–melanocortin system, which regulates body weight. Pro-opiomelanocortin (POMC)-derived neurohormones act as ligands for melanocortin receptors (MCRs), regulating the leptin–melanocortin pathway through protein–protein interactions. Loss-of-function mutations in the genes encoding POMC, MC3R, and MC4R can lead to the dysregulation of energy expenditure and feeding balance, early-onset obesity, and developmental dysregulation. Recent studies have identified new genetic regulatory mechanisms and potential biomarker regions for the POMC gene and MC4R secondary messenger pathway associated with obesity. Recent advances in crystal structure studies have enhanced our understanding of the protein interactions in this pathway. This narrative review focuses on recent developments in two key areas related to POMC regulation and the leptin–melanocortin pathway: (1) genetic variations in and functions of POMC, and (2) MC3R and MC4R variants that lead to genetic obesity in humans. Understanding these novel mutations in POMC and MC4R/MC3R, as well as their structural and intracellular mechanisms, may help identify strategies for the treatment and diagnosis of obesity, particularly childhood obesity. Full article