Adiponectin and cardiomyocyte

Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery ligation. We studied the molecular mechanisms underlying adiponectin's cardio-protective effects in adiponectin knockout (Ad-KO) compared with wild-type (WT) mice subjected to ischemia by coronary artery ligation and H9c2 cardiomyocyte cell line exposed to hypoxia. Systemic infusion of a cathepsin-B activatable near-infrared probe as a biomarker for autophagy and detection via noninvasive three-dimensional fluorescence molecular tomography combined with computerized tomography to quantitate temporal changes, indicated increased activity in the myocardium of WT mice after myocardial infarction which was attenuated in Ad-KO...

Circadian time of intake determines the cardioprotective outcome of glucocorticoids in normal and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) is genetically required to preserve normal heart function in the long-term. The GR co-factor KLF15 is a pleiotropic regulator of cardiac metabolism. However, the cardiomyocyte-autonomous metabolic targets of the GR-KLF15 concerted epigenetic action remain undefined. Here we report that circadian time of intake determines the activation of a transcriptional and functional glucose oxidation program in heart by the glucocorticoid prednisone with comparable magnitude between sexes...

AIMS: Adiponectin has been shown to mediate cardioprotective effects and levels are typically reduced in patients with cardiometabolic disease. Hence, there has been intense interest in developing adiponectin-based therapeutics. The aim of this translational research study was to examine the functional significance of targeting adiponectin signaling with the adiponectin receptor agonist ALY688 in a mouse model of heart failure with reduced ejection fraction (HFrEF), and the mechanisms of cardiac remodeling leading to cardioprotection...

Little evidence demonstrated the effects of nitric oxide (NO) hydrogel with adipocytes in vivo. We aimed to investigate the effects of adiponectin (ADPN) and CCR2 antagonist on cardiac functions and macrophage phenotypes after myocardial infarction (MI) using chitosan caged nitric oxide donor (CSNO) patch with adipocytes. 3T3-L1 cell line was induced to adipocytes and ADPN expression was knocked down. CSNO was synthesized and patch was constructed. MI model was constructed and patch was placed on the infarcted area...

BACKGROUND: Myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlying molecular mechanisms remain unclear. Recent studies demonstrate that the diabetic heart is resistant to other cardioprotective interventions, including adiponectin and preconditioning. The "universal" resistance to multiple therapeutic interventions suggests impairment of the requisite molecule(s) involved in broad prosurvival signaling cascades. Cav (Caveolin) is a scaffolding protein coordinating transmembrane signaling transduction...

BACKGROUND: Obesity-related diseases have important implications for the occurrence, severity, and outcome of ischemic heart disease. Patients with obesity, hyperlipidemia, and diabetes mellitus (metabolic syndrome) are at increased risk of heart attack with decreased plasma lipocalin levels, and lipocalin is negatively correlated with heart attack incidence. APPL1 is a signaling protein with multiple functional structural domains and plays an important role in the APN signaling pathway...

Cardiovascular diseases (CVDs) are a series of diseases induced by inflammation and lipid metabolism disorders, among others. Metabolic diseases can cause inflammation and abnormal lipid metabolism. C1q/TNF-related proteins 1 (CTRP1) is a paralog of adiponectin that belongs to the CTRP subfamily. CTRP1 is expressed and secreted in adipocytes, macrophages, cardiomyocytes, and other cells. It promotes lipid and glucose metabolism but has bidirectional effects on the regulation of inflammation. Inflammation can also inversely stimulate CTRP1 production...

Cardiovascular disease (CVD) is a common disease that seriously threatens the health of human beings, especially middle-aged and elderly people over 50 years old. It has the characteristics of high prevalence, high disability rate and high mortality rate. Previous studies have shown that adiponectin has therapeutic effects on a variety of CVDs. As a key adipokine, adiponectin, is an abundant peptide-regulated hormone that is mainly released by adipocytes and cardiomyocytes, as well as endothelial and skeletal cells...

Adiponectin is a cytokine produced by adipocytes and acts as a potential cardioprotective agent and plays an important role in myocardial ischemia/reperfusion injury. In a myocardial hypoxia/reoxygenation model using neonatal rat ventricular myocytes, we investigated the contribution of adiponectin-mediated autophagy to its cardioprotective effects. Cardiomyocytes were exposed to hypoxia/reoxygenation pretreated with or without adiponectin in the presence of absence of rapamycin. Cell viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method...

Contraction band necrosis (CBN) is a common abnormality found in the myocardium of cocaine abusers, but is rarely reported in experimental models of cocaine abuse. Connexin 43 (Cx43) is essential for cardiac intercellular communication and the propagation of CBN. Under stress or injury, cardiac Cx43 is dephosphorylated, which is related to cardiomyocyte dysfunction and pathogenesis, whereas adiponectin exerts beneficial effects in the myocardium. In this study, we explore the effects of cocaine on cardiac Cx43 in vivo...

OBJECTIVE: To investigate the regulation of adiponectin/miR-711 on TLR4/NF-κB-mediated inflammatory response and diabetic cardiomyocyte apoptosis. METHODS: Diabetes models were established using rats and H9c2 cardiomyocytes. qRT-PCR was used to detect adiponectin, miR-711, and TLR4. MTT, β-galactosidase staining, and flow cytometry were utilized to assess cell viability, senescence, and apoptosis, respectively. The colorimetric method was used to measure caspase-3 activity, DCFH-DA probes to detect ROS, and western blotting to determine the protein levels of Bax, Bcl-2, TLR4, and p-NF-κB p65...

The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin. One of the key adipokines is adiponectin, the abundant peptide regulating hormone that is released mainly by adipocytes and cardiomyocytes as well as by endothelial and skeletal cells...

Visceral adipose tissue (VAT) is a metabolic organ known to regulate fat mass, and glucose and nutrient homeostasis. VAT is an active endocrine gland that synthesizes and secretes numerous bioactive mediators called 'adipocytokines/adipokines' into systemic circulation. These adipocytokines act on organs of metabolic importance like the liver and skeletal muscle. Multiple preclinical and in vitro studies showed strong evidence of the roles of adipocytokines in the regulation of metabolic disorders like diabetes, obesity and insulin resistance...

BACKGROUND: Despite significantly reduced acute myocardial infarction (MI) mortality in recent years, ischemic heart failure continues to escalate. Therapeutic interventions effectively reversing pathological remodeling are an urgent unmet medical need. We recently demonstrated that AdipoR1 (APN [adiponectin] receptor 1) phosphorylation by GRK2 (G-protein-coupled receptor kinase 2) contributes to maladaptive remodeling in the ischemic heart. The current study clarified the underlying mechanisms leading to AdipoR1 phosphorylative desensitization and investigated whether blocking AdipoR1 phosphorylation may restore its protective signaling, reversing post-MI remodeling...

Whether and how sevoflurane preconditioning (SevoPre) exerts protection against acute myocardial ischemia/reperfusion (MI/R) injury remains elusive. We observed significant myocardial injury, as evidenced by infarct size, cardiomyocyte apoptosis, and circulating troponin-I, at 3 h of MI/R in both wildtype and adiponectin knockout mice. The injury was significantly ameliorated by SevoPre in wildtype mice, but not in adiponectin knockout mice. In wildtype mice, we found that MI/R could increase endoplasmic reticulum stress of cardiomyocytes, and impair association of adiponectin receptor 1 and ceveolin-3, both of which processes were largely restored by SevoPre...

Accumulation of lipids and their metabolites induces lipotoxicity in diabetic cardiomyopathy. Lowering ceramide concentration could reduce the impact of metabolic damage to target organs. Adiponectin improves lipotoxicity through its receptors (AdiopRs), which have sequence homology with ceramidase enzymes. Therefore, cardioprotective role of AdipoR agonism by AdipoRon was investigated. Sixteen-week-old male db/m and db/db mice were fed a diet containing AdipoRon for four weeks. Phenotypic and metabolic profiles with associated cellular signaling pathways involved in lipid metabolism were investigated in the mice heart and human cardiomyocytes to establish treatment effect of AdipoRon...

Background: Acute myocardial infarction (AMI) patients suffer systemic metabolic dysfunction via incompletely understood mechanisms. Adipocytes play critical role in metabolic homeostasis. The impact of AMI upon adipocyte function is unclear. Small extracellular vesicles (sEV) critically contribute to organ-organ communication. Whether and how sEV mediate post-MI cardiomyocyte/adipocyte communication remain unknown. Methods Plasma sEV were isolated from sham control (Pla-sEVSham ) or 3 hours after myocardial ischemia/reperfusion (Pla-sEVMI/R ) and incubated with adipocytes for 24 hours...

The aim of the present study was to examine whether adiponectin could inhibit cardiomyocyte senescence induced by D‑galactose (D‑gal), and whether it functioned via the adiponectin receptor 1 (AdipoR1)/adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) signaling pathway. For this purpose, the expression levels of adiponectin, AdipoR1 and APPL1 in mouse plasma and myocardial tissues were detected via reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting...

Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β1 -adrenergic receptor autoantibody (β1 -AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β1 -AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up-regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β1 -AA by up-regulating the level of AMPK phosphorylation...

Adiponectin is a small peptide secreted and a key component of the endocrine system and immune system. Although globular adiponectin protects myocardial ischemia/reperfusion-induced cardiomyocyte injury, the protective mechanisms remain largely unresolved. Using a neonatal rat ventricular myocyte hypoxia/reoxygenation model, we investigated the role of its potential mechanisms of necroptosis in globular adiponectin-mediated protection in hypoxia/reoxygenation-induced cardiomyocyte injury as compared to apoptosis...