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Problemy Endokrinologii Aug 2023Adipomyokines are synthesized and secreted into the bloodstream by cells of both muscle and adipose tissue. They can have both a negative metabolic effect, acting as...
BACKGROUND
Adipomyokines are synthesized and secreted into the bloodstream by cells of both muscle and adipose tissue. They can have both a negative metabolic effect, acting as pro-inflammatory adipokines in obesity, and a positive one, increasing in response to physical exertion in the form of myokines.
AIM
To study the features of adipocytokine secretion in children with constitutionally exogenous obesity.
MATERIALS AND METHODS
The study included 80 patients: 60 adolescents aged 15 [13; 16] years with constitutionally exogenous obesity SDS BMI: 3.0 [2.6; 3.3] and 20 control group children aged 16 [15; 17] years without excess weight SDS BMI: -0.3 [-1.25; 0.33]. Commercial enzyme immunoassay kits were used to determine the level of adipomyokines. The compositional composition of the body was evaluated by bioimpedance analysis (InBody 770 analyzer, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoft Inc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05.
RESULTS
Levels of IL-6 and irisin are statistically significantly higher in obese adolescents compared to the control group: 0.55 [0.226; 1.35] pg/ml vs 0.202 [0.128; 0.652] pg/ml (p=0.041) and 11.16 [6.6; 22.76] mcg/ml vs 7.36 [6.48; 9.68] mcg/ml (p=0.043), respectively. Concentrations of IL-6, myostatin and decorin increase with an increase in the degree of obesity: grade I vs III: 0.226 [0.224; 0.398] vs 0.80 [0.36; 1.81] pg/ml (p=0,0197), 25,85 [21,53; 28,23] vs 31.41 [24.36; 35.06] ng/ml (p=0.03), 4065.3 [3244.9; 5245.5] vs 5322.5 [4199.8; 7702.4] pg/ml (p=0.0376), respectively. In obese children, IL-6 levels positively correlate with BMI, SDS BMI and the amount of adipose tissue, and myostatin - with BMI and SDS BMI. The concentration of irisin in the blood serum is significantly higher in obese girls than in obese boys and healthy girls. Obese patients, compared with lean peers, are characterized by a statistically significantly higher content of both fat and lean mass. With the progression of obesity, there is a statistically significant increase in the ratio of fat to lean mass (I degree - 0.66 [0.56; 0.7], III - 0.78 [0.68; 0.98] (p=0.0073).
CONCLUSION
Patients with obesity and normal body weight have different levels of adipomyokines. An increase in the level of IL-6 with the progression of obesity is directly related to an increase in the content of adipose tissue. Further study of the features of adipocytokine secretion, their relationship with the features of the body composition and metabolic complications in obesity is required.
Topics: Child; Adolescent; Male; Female; Humans; Myostatin; Fibronectins; Interleukin-6; Pediatric Obesity; Adipokines
PubMed: 37694871
DOI: 10.14341/probl13250 -
Antioxidants (Basel, Switzerland) Nov 2023Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes:... (Review)
Review
Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.
PubMed: 38136166
DOI: 10.3390/antiox12122046 -
Heliyon Apr 2023Hypermobility involves excessive flexibility and systemic manifestations of connective tissue fragility. We propose a folate-dependent hypermobility syndrome model based...
Hypermobility involves excessive flexibility and systemic manifestations of connective tissue fragility. We propose a folate-dependent hypermobility syndrome model based on clinical observations, and through a review of existing literature, we raise the possibility that hypermobility presentation may be dependent on folate status. In our model, decreased methylenetetrahydrofolate reductase (MTHFR) activity disrupts the regulation of the ECM-specific proteinase matrix metalloproteinase 2 (MMP-2), leading to high levels of MMP-2 and elevated MMP-2-mediated cleavage of the proteoglycan decorin. Cleavage of decorin leads ultimately to extracellular matrix (ECM) disorganization and increased fibrosis. This review aims to describe relationships between folate metabolism and key proteins in the ECM that can further explain the signs and symptoms associated with hypermobility, along with possible treatment with 5-methyltetrahydrofolate supplementation.
PubMed: 37095957
DOI: 10.1016/j.heliyon.2023.e15387 -
Veterinary Sciences Mar 2023The aim of this study was to investigate whether using immunohistochemistry to detect the angiogenic proteins vascular endothelial growth factor (VEGF) and decorin can...
The aim of this study was to investigate whether using immunohistochemistry to detect the angiogenic proteins vascular endothelial growth factor (VEGF) and decorin can help predict the risk of local recurrence of, or death from, canine soft tissue sarcoma (STS). VEGF and decorin were detected using validated immunohistochemical methods on 100 formalin-fixed paraffin-embedded samples of canine STS. The tumours had been resected previously, with clinical outcome determined by questionnaire. Each slide was assessed by light microscopy and the pattern of immunostaining with VEGF and decorin determined. Patterns of immunostaining were then analysed to detect associations with outcome measures of local recurrence and tumour-related death. High VEGF immunostaining was significantly ( < 0.001) associated with both increased local recurrence and reduced survival time. The distribution of decorin immunostaining within the tumour was significantly associated with survival time ( = 0.04) and local tumour recurrence ( = 0.02). When VEGF and decorin scores were combined, STS with both high VEGF and low decorin immunostaining were more likely to recur or cause patient death ( < 0.001). The results of this study suggest that immunostaining of VEGF and decorin may help predict the risk of local recurrence of canine STS.
PubMed: 37104411
DOI: 10.3390/vetsci10040256 -
International Journal of Molecular... Jun 2023Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are... (Review)
Review
Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are key players in chondral diseases, specifically in the degradation of the extracellular matrix. Evaluating proteoglycan molecules can serve as a biomarker for joint degradation in osteoarthritis patients, as well as assessing the quality of repaired tissue following different treatment strategies for chondral injuries. Despite ongoing research, understanding osteoarthritis and cartilage repair remains unclear, making the identification of key molecules essential for early diagnosis and effective treatment. This review offers an overview of proteoglycans as primary molecules in articular cartilage. It describes the various types of proteoglycans present in both healthy and damaged cartilage, highlighting their roles. Additionally, the review emphasizes the importance of assessing proteoglycans to evaluate the quality of repaired articular tissue. It concludes by providing a visual and narrative description of aggrecan distribution and presence in healthy cartilage. Proteoglycans, such as aggrecan, biglycan, decorin, perlecan, and versican, significantly contribute to maintaining the health of articular cartilage and the cartilage repair process. Therefore, studying these proteoglycans is vital for early diagnosis, evaluating the quality of repaired cartilage, and assessing treatment effectiveness.
Topics: Humans; Aggrecans; Cartilage, Articular; Decorin; Extracellular Matrix Proteins; Biglycan; Osteoarthritis; Cartilage Diseases; Lectins, C-Type
PubMed: 37446002
DOI: 10.3390/ijms241310824 -
International Journal of Molecular... Sep 2021Two small leucine-rich proteoglycans (SLRP), decorin and biglycan, play important roles in structural-functional integrity of the placenta and fetal membranes, and their... (Review)
Review
Two small leucine-rich proteoglycans (SLRP), decorin and biglycan, play important roles in structural-functional integrity of the placenta and fetal membranes, and their alterations can result in several pregnancy-associated diseases. In this review, we briefly discuss normal placental structure and functions, define and classify SLRPs, and then focus on two SLRPs, decorin (DCN) and biglycan (BGN). We discuss the consequences of deletions/mutations of DCN and BGN. We then summarize DCN and BGN expression in the pregnant uterus, myometrium, decidua, placenta, and fetal membranes. Actions of these SLRPs as ligands are then discussed in the context of multiple binding partners in the extracellular matrix and cell surface (receptors), as well as their alterations in pathological pregnancies, such as preeclampsia, fetal growth restriction, and preterm premature rupture of membranes. Lastly, we raise some unanswered questions as food for thought.
Topics: Animals; Biglycan; Decorin; Female; Fetal Growth Retardation; Gene Expression Regulation; Humans; Mutation; Placenta; Pre-Eclampsia; Pregnancy
PubMed: 34638928
DOI: 10.3390/ijms221910584 -
Placenta Feb 2020Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the...
INTRODUCTION
Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the mother, is often undiagnosed prior to delivery. We tested several potential biomarkers in plasma from PAS mothers to determine whether any were sufficiently robust for a formal, diagnostic accuracy study.
METHODS
We examined hyperglycosylated hCG (h-hCG), decorin and IL-8, based on biological plausibility and literature indications that they might be altered in PAS. These analytes were assayed by ELISA in maternal plasma from five groups, comprising (1) normal term controls, (2) placenta previa controls, and cases of (3) placenta increta/percreta without placenta previa, (4) placenta previa increta/percreta and (5) placenta previa accreta.
RESULTS
There were no differences in h-hCG, ß-hCG or the h-hCG/ß-hCG ratio between the groups. Mean decorin levels were increased in previa controls (Group 2) compared to the other groups, but there was substantial overlap between the individual values. While an initial multiplex assay showed a greater value for IL-8 in the placenta previa increta/percreta group (Group 4) compared to placenta previa controls (Group 2), the subsequent validation ELISA for IL-8 showed no differences between the groups.
DISCUSSION
We conclude that the absence of differences and the extent of overlap between cases and controls does not justify further assessment of these biomarkers.
Topics: Adult; Biomarkers; Chorionic Gonadotropin; Decorin; Female; Humans; Interleukin-8; Placenta Accreta; Placenta Previa; Pregnancy
PubMed: 32174305
DOI: 10.1016/j.placenta.2020.01.007 -
American Journal of Physiology. Cell... Mar 2022Decorin is a stromal-derived prototype member of the small leucine-rich proteoglycan gene family. In addition to its functions as a regulator of collagen fibrillogenesis... (Review)
Review
Decorin is a stromal-derived prototype member of the small leucine-rich proteoglycan gene family. In addition to its functions as a regulator of collagen fibrillogenesis and TGF-β activity soluble decorin acts as a pan-receptor tyrosine kinase (RTK) inhibitor. Decorin binds to various RTKs including EGFR HER2 HGFR/Met VEGFR2 TLR and IGFR. Although the molecular mechanism for the action of decorin on these receptors is not entirely elucidated overall decorin evokes transient activation of these receptors with suppression of downstream signaling cascades culminating in growth inhibition followed by their physical downregulation via caveosomal internalization and degradation. In the case of Met decorin leads to decreased β-catenin signaling pathway and growth suppression. As most of these RTKs are responsible for providing a growth advantage to cancer cells the result of decorin treatment is oncosuppression. Another decorin-driven mechanism to restrict cancer growth and dissemination is by impeding angiogenesis via vascular endothelial growth factor receptor 2 (VEGFR2) and the concurrent activation of protracted endothelial cell autophagy. In this review we will dissect the multiple roles of decorin in cancer biology and its potential use as a next-generation protein-based adjuvant therapy to combat cancer.
Topics: Autophagy; Carrier Proteins; Decorin; Extracellular Matrix Proteins; Humans; Neoplasms; Receptor Protein-Tyrosine Kinases; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 35171698
DOI: 10.1152/ajpcell.00016.2022 -
Frontiers in Cell and Developmental... 2023Collagen XII, a fibril-associated collagen with interrupted triple helices (FACIT), influences fibrillogenesis in numerous tissues. In addition to this extracellular... (Review)
Review
Collagen XII, a fibril-associated collagen with interrupted triple helices (FACIT), influences fibrillogenesis in numerous tissues. In addition to this extracellular function, collagen XII also directly regulates cellular function. Collagen XII is widely expressed in connective tissues, particularly tendons, ligaments, and the periodontium and periosteum, where it is enriched in the pericellular regions. Mutations in the collagen XII gene cause myopathic Ehlers-Danlos syndrome (mEDS), an early-onset disease characterized by overlapping connective tissue abnormalities and muscle weakness. Patients with mEDS exhibit delayed motor development, muscle weakness, joint laxity, hypermobility, joint contractures, and abnormal wound healing. A mEDS mouse model was generated by deletion of the gene, resulting in skeletal and muscle abnormalities with disorganized tissue structures and altered mechanical properties. Extracellularly, collagen XII interacts with collagen I fibrils and regulates collagen fibril spacing and assembly during fibrillogenesis. Evidence for the binding of collagen XII to other EDS-related molecules (e.g., decorin and tenascin X) suggests that disruption of ECM molecular interactions is one of the causes of connective tissue pathology in mEDS. Collagen XII also has been shown to influence cell behavior, such as cell shape and cell-cell communication, by providing physical connection between adjacent cells during tissue development and regeneration. The focus of this review is on the functions of collagen XII in development, regeneration, and disease.
PubMed: 36936682
DOI: 10.3389/fcell.2023.1129000 -
Biomolecules Feb 2021The insulin-like growth factor (IGF) system is a dynamic network of proteins, which includes cognate ligands, membrane receptors, ligand binding proteins and functional... (Review)
Review
The insulin-like growth factor (IGF) system is a dynamic network of proteins, which includes cognate ligands, membrane receptors, ligand binding proteins and functional downstream effectors. It plays a critical role in regulating several important physiological processes including cell growth, metabolism and differentiation. Importantly, alterations in expression levels or activation of components of the IGF network are implicated in many pathological conditions including diabetes, obesity and cancer initiation and progression. In this review we will initially cover some general aspects of IGF action and regulation in cancer and then focus in particular on the role of transcriptional regulators and novel interacting proteins, which functionally contribute in fine tuning IGF1R signaling in several cancer models. A deeper understanding of the biological relevance of this network of IGF1R modulators might provide novel therapeutic opportunities to block this system in neoplasia.
Topics: Disease Progression; Humans; Ligands; Neoplasms; Protein Binding; Receptor, IGF Type 1; Signal Transduction; Somatomedins
PubMed: 33673232
DOI: 10.3390/biom11020273