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Biomedicine & Pharmacotherapy =... Jul 2023Dementia is a detrimental neuropathologic condition with considerable physical, mental, social, and financial impact on patients and society. Patients with metabolic... (Review)
Review
Dementia is a detrimental neuropathologic condition with considerable physical, mental, social, and financial impact on patients and society. Patients with metabolic syndrome (MetS), a group of diseases that occur in tandem and increase the risk of neurologic diseases, have a higher risk of dementia. The ratio between muscle and adipose tissue is crucial in MetS, as these contain many hormones, including myokines and adipokines, which are involved in crosstalk and local paracrine/autocrine interactions. Evidence suggests that abnormal adipokine and myokine synthesis and release may be implicated in various MetS, such as atherosclerosis, diabetic mellitus (DM), and dyslipidemia, but their precise role is unclear. Here we review the literature on adipokine and myokine involvement in MetS-induced dementia via glucose and insulin homeostasis regulation, neuroinflammation, vascular dysfunction, emotional changes, and cognitive function.
Topics: Humans; Adipokines; Metabolic Syndrome; Adipose Tissue; Muscle, Skeletal; Dementia
PubMed: 37150030
DOI: 10.1016/j.biopha.2023.114847 -
Journal of Affective Disorders Nov 2023To study the relationship between clock genes and Major Depressive Disorder (MDD).
OBJECTIVE
To study the relationship between clock genes and Major Depressive Disorder (MDD).
METHODS
GEO database was used to obtain the chip data and clinical information of datasets GSE98793, GSE39653 and GSE52790. The differentially expressed clock genes were found through the analysis of the differentially expressed genes between MDD and healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) enrichment analysis were performed on the differential expressed clock genes. Lasso Regression and Support Vector Machine (SVM) method were used for screening the differential expressed clock genes. Logistic regression was used to establish a diagnostic model for depression with the screened genes. Receiver Operating Characteristic (ROC) Curve was used to verify the model. Gene differential expression analysis was performed for MDD with high scores and MDD with low scores in the diagnostic model. Gene Set Enrichment Analysis (GSEA) enrichment analysis was performed for differentially expressed genes. Single-gene GSEA was used to analyze each gene in the model separately. Cibersort method was used to analyze the immune infiltration of MDD and healthy controls, and the correlation between immune cells and clock genes was analyzed. Cytoscape was used to analyze the clock gene interaction network. The DGIdb website was used to predict potentially effective therapeutic drugs for clock genes closely related to MDD.
RESULTS
Six genes were identified by differential expression analysis of clock genes between MDD and healthy controls. GO and KEGG enrichment analysis of 6 genes showed that their pathways were concentrated such as circadian rhythm, rhythmic process, TGF - beta signaling pathway, longevity regulating pathway-multiple species, adipocytokine signaling pathway and so on. Lasso regression and SVM were used to screen out 5 clock genes (HDAC1, ID3, NFIL3, PRKAA1, TNF) for MDD. The diagnostic model of depression was established according to the 5 clock genes. The area under the curve (AUC) of the established depression diagnostic model was 0.686. Gene difference analysis was performed between MDD patients with high score of clock gene diagnostic model and MDD patients with low score. GSEA was performed for the differential genes showed that the most enriched pathways were:adipocytokine signaling pathway, TGF beta signaling pathway, oxidative phosphorylation, primary immunodeficiency, and so on. The single gene GSEA showed that the most enriched pathways were Toll like receptor signaling pathway, glucolipid metabolism, amino acid metabolism, neuroactive ligand receptor interaction, and so on. The results of immune infiltration analysis showed that NK cells resting and Macrophages M2 were different between MDD and control groups. In MDD, the gene closely related to NK cells resting was HDAC1, and the genes closely related to Macrophages M2 were HDAC1 and NFIL3. The RNA interactions network of clock genes shows that the regulation process is complex, which can provide a reference for subsequent related research. Potential therapeutic drugs predict display, among the 5 clock genes, TNF, HDAC1, and PRKAA1 may have potential effective therapeutic drugs.
CONCLUSION
Among all CLOCK genes, HDAC1, ID3, NFIL3, PRKAA1, TNF are closely related to MDD. Among them, TNF, HDAC1, and PRKAA1 may have potential effective therapeutic drugs.
Topics: Humans; Depressive Disorder, Major; Area Under Curve; Circadian Rhythm; Control Groups; Adipokines
PubMed: 37633529
DOI: 10.1016/j.jad.2023.08.113 -
Cancer Epidemiology, Biomarkers &... Oct 2023Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the...
BACKGROUND
Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.
METHODS
Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).
RESULTS
Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002).
CONCLUSIONS
High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.
IMPACT
Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
Topics: Male; Humans; Female; Leptin; Adiponectin; Adipokines; Receptors, Adiponectin; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Receptors, Leptin
PubMed: 37555827
DOI: 10.1158/1055-9965.EPI-23-0505 -
Frontiers in Immunology 2023Perivascular adipose tissue and the vessel wall are connected through intricate bidirectional paracrine and vascular secretory signaling pathways. The secretion of... (Review)
Review
Perivascular adipose tissue and the vessel wall are connected through intricate bidirectional paracrine and vascular secretory signaling pathways. The secretion of inflammatory factors and oxidative products by the vessel wall in the diseased segment has the ability to influence the phenotype of perivascular adipocytes. Additionally, the secretion of adipokines by perivascular adipose tissue exacerbates the inflammatory response in the diseased vessel wall. Therefore, quantitative and qualitative studies of perivascular adipose tissue are of great value in the context of vascular inflammation and may provide a reference for the assessment of cardiovascular ischemic disease.
Topics: Humans; Cardiovascular Diseases; Adipokines; Adipose Tissue; Adipocytes; Signal Transduction
PubMed: 37822930
DOI: 10.3389/fimmu.2023.1271051 -
Cells Oct 2023Adiponectin (adipoq), the most abundant hormone in circulation, has many beneficial effects on the cardiovascular system, in part by preserving the contractile phenotype...
Adiponectin (adipoq), the most abundant hormone in circulation, has many beneficial effects on the cardiovascular system, in part by preserving the contractile phenotype of vascular smooth muscle cells (VSMCs). However, the lack of adiponectin or its receptor and treatment with recombinant adiponectin have shown contradictory effects on plaque in mice. RNA sequence of and VSMCs from male aortas identified a critical role for adiponectin in AKT signaling, the extracellular matrix (ECM), and TGF-β signaling. Upregulation of AKT activity mediated proliferation and migration of cells. Activation of AMPK with metformin or AdipoRon reduced AKT-dependent proliferation and migration of cells but did not improve the expression of contractile genes. Adiponectin deficiency impaired oxidative phosphorylation (OXPHOS), increased expression of glycolytic enzymes, and elevated mitochondrial reactive oxygen species (ROS) (superoxide, and hydrogen peroxide). Anti-atherogenic mechanisms targeted the ECM in cells, downregulating MMP2 and 9 and upregulating decorin (DCN) and elastin (ELN). In vivo, the main sex differences in protein expression in aortas involved a more robust upregulation of MMP3 in females than males. Females also showed a reduction in DCN, which was not affected in males. Our study uncovered the AKT/MAPK/TGF-β network as a central regulator of VSMC phenotype.
Topics: Male; Mice; Female; Animals; Adiponectin; Proto-Oncogene Proteins c-akt; Muscle, Smooth, Vascular; Phenotype; Transforming Growth Factor beta
PubMed: 37887338
DOI: 10.3390/cells12202493 -
Aging Dec 2023Pyroptosis, a newly discovered programmed cell death process, is characterized by NLRP3 inflammasome activation and pro-inflammatory mediator release. Nucleus pulposus...
Pyroptosis, a newly discovered programmed cell death process, is characterized by NLRP3 inflammasome activation and pro-inflammatory mediator release. Nucleus pulposus (NP) cell pyroptosis is an important cause of intervertebral disc degeneration (IDD). Adiponectin (APN) is an adipokine and has an anti-inflammatory effect. However, whether and how APN protects against NP cell pyroptosis remains unexplored. Our results showed that human degenerated NP tissue displayed a significant increase in the protein levels of NLRP3, caspase-1 and GSDMD-N. APN expression was down-regulated in human degenerated NP tissue and NP cells challenged with lipopolysaccharide (LPS). Lentivirus-mediated overexpression of APN increased miR-135a-5p levels, decreased thioredoxin-interacting protein (TXNIP) expression and its interaction with NLRP3, and inhibited pyroptosis in human NP cells stimulated with LPS. TXNIP was identified as a direct target of miR-135a-5p. The inhibitory effects of APN on pyroptosis were reversed by pretreatment with miR-135a-5p inhibitor or lentiviral vector expressing TXNIP in LPS-treated human NP cells. In summary, these data suggest that APN restrains LPS-induced pyroptosis through the miR-135a-5p/TXNIP signaling pathway in human NP cells. Increasing APN levels could be a new approach to retard IDD.
Topics: Humans; Adiponectin; Carrier Proteins; Intervertebral Disc Degeneration; Lipopolysaccharides; MicroRNAs; NLR Family, Pyrin Domain-Containing 3 Protein; Nucleus Pulposus; Pyroptosis; Signal Transduction
PubMed: 38048212
DOI: 10.18632/aging.205226 -
The American Journal of Sports Medicine Oct 2023Adipokines represent a spectrum of bioactive molecules that could modulate fibroblastic and inflammatory processes. The role of adipokines in the pathogenesis of frozen...
BACKGROUND
Adipokines represent a spectrum of bioactive molecules that could modulate fibroblastic and inflammatory processes. The role of adipokines in the pathogenesis of frozen shoulder (FS), a common musculoskeletal disorder characterized by chronic inflammation, remains obscure.
PURPOSE
To evaluate whether adipokines contribute to the pathogenic mechanisms of FS and to evaluate any potential correlation of adipokines with patients' symptoms.
STUDY DESIGN
Controlled laboratory study.
METHODS
Shoulder capsule specimens were obtained from 10 patients with FS and 10 patients with shoulder instability (control group). The specimens were dyed using hematoxylin and eosin and immunohistochemically assessed with antibodies targeting adipokines, collagen I, collagen III, and tumor necrosis factor α. Immunoreactivity was graded from "no" to "strong" in a blinded manner. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) analysis was conducted. Before the surgery, patient-reported frequency of pain, severity of pain, stiffness, and shoulder range of motion were documented.
RESULTS
In comparison with the control group, patients with FS had significantly greater pain frequency, pain severity, and stiffness and more limited shoulder range of motion ( < .001). Hematoxylin and eosin- and Masson trichrome-stained samples from the FS group displayed hypercellularity and increased collagen fibers. Immunohistochemistry and RT-qPCR analyses indicated that expression of adipokines was significantly increased in FS capsules compared with the control group. The expression of collagen I, collagen III, and tumor necrosis factor α was also increased in FS capsules. No significant correlation was noted between adipokine expression and patient-reported outcomes in the control group, whereas in patients with FS, adiponectin expression was correlated with pain frequency ( = 0.78; = .01) and stiffness ( = 0.73; = .02). Visfatin was also correlated with pain frequency ( = 0.70; = .02).
CONCLUSION/CLINICAL RELEVANCE
This study indicated a potential role for adipokines in the pathogenesis of FS and demonstrated a correlation between adipokine expression and patients' pain and stiffness.
Topics: Humans; Adipokines; Joint Instability; Tumor Necrosis Factor-alpha; Eosine Yellowish-(YS); Hematoxylin; Shoulder Joint; Bursitis; Pain
PubMed: 37615177
DOI: 10.1177/03635465231189797 -
Annales D'endocrinologie Jun 2024We currently have a large sum of clinical and experimental data documenting the involvement of numerous adipokines in the maintenance of energy homeostasis in healthy... (Review)
Review
We currently have a large sum of clinical and experimental data documenting the involvement of numerous adipokines in the maintenance of energy homeostasis in healthy individuals and their dysregulation in diseases such as obesity, metabolic syndrome or type 2 diabetes. Despite the impressive discoveries made in this field over many years, much remains to be done before understanding all the physiological and pathological implications, and hoping for the development of other effective and safe therapeutic strategies. Two original adipokines will be taken as examples to illustrate these remarks, chemerin and neuregulin 4.
Topics: Humans; Adipokines; Adipose Tissue; Obesity; Biomarkers; Chemokines; Neuregulins; Diabetes Mellitus, Type 2; Intercellular Signaling Peptides and Proteins; Animals; Metabolic Syndrome
PubMed: 38614158
DOI: 10.1016/j.ando.2024.04.002 -
Journal of Diabetes and Its... Nov 2023Asprosin, encoded by penultimate two exons (exon 65 and exon 66) of the gene Fibrillin 1 (FBN1), has been recently discovered to be a novel hormone secreted by white... (Review)
Review
Asprosin, encoded by penultimate two exons (exon 65 and exon 66) of the gene Fibrillin 1 (FBN1), has been recently discovered to be a novel hormone secreted by white adipose tissues during fasting. The glucose metabolism disorders are often accompanied by increased asprosin level. Previous research suggests that asprosin may contribute to the development of diabetes by regulating glucose homeostasis, appetite, insulin secretion, and insulin sensitivity. In this review, we summarize the recent findings from studies on asprosin and its association with Type 2 diabetes mellitus, and discusses its mechanisms from various aspects, so as to provide clinical diagnosis and treatment ideas for T2DM.
Topics: Humans; Adipokines; Diabetes Mellitus, Type 2; Peptide Hormones; Glucose; Insulin Resistance
PubMed: 37769508
DOI: 10.1016/j.jdiacomp.2023.108614 -
Frontiers in Endocrinology 2023Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP...
INTRODUCTION
Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans .
METHODS
Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial.
RESULTS
Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion , indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release.
DISCUSSION
The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under ).
Topics: Humans; Male; Adipocytes; Adipose Tissue; Atrial Natriuretic Factor; Leptin; Lipolysis
PubMed: 37455918
DOI: 10.3389/fendo.2023.1195677