ABSTRACT
Apelin is an endogenous ligand of G protein-coupled receptor APJ. Apelin/APJ system is widely expressed in abundant tissues, especially bone, joint and muscle tissue. This review focus on the effects of apelin/APJ system on locomotor system. An increasing number of evidence suggests that apelin/APJ system plays a crucial role in many physiological and pathological processes of locomotor system. Physiologically, apelin/APJ system promotes bone formation, muscle metabolism and skeletal muscle production. Pathologically, apelin/APJ system exacerbates osteoarthritis pathogenesis, whereas it alleviates osteoporosis. Besides, the level of apelin expression is regulated by different training modes, including continuous aerobic exercise, high-intensity interval training and resistance exercises. More importantly, exercise-induced apelin may be a potent pharmacological agent for the treatment of diseases and the regulation of physiological processes. Considering the pleiotropic effects of apelin on locomotor system, apelin/APJ system may be an important therapeutic target for locomotor system diseases.
Subject(s)
Apelin Receptors/metabolism , Apelin/metabolism , Musculoskeletal Diseases/drug therapy , Animals , Apelin/agonists , Apelin/antagonists & inhibitors , Apelin Receptors/agonists , Apelin Receptors/antagonists & inhibitors , Disease Models, Animal , Humans , Molecular Targeted Therapy/methods , Musculoskeletal Diseases/pathology , Signal Transduction/drug effectsABSTRACT
Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmonary edema, asthma, and chronic obstructive pulmonary diseases. In detail, apelin/APJ system attenuates PAH by activating AMPK-KLF2-eNOS-NO signaling and miR424/503-FGF axis. Also, apelin protects against ALI/ARDS by reducing mitochondrial ROS-triggered oxidative damage, mitochondria apoptosis, and inflammatory responses induced by the activation of NF-κB and NLRP3 inflammasome. Apelin/APJ system also prevents the occurrence of pulmonary edema via activating AKT-NOS3-NO pathway. Moreover, apelin/APJ system accelerates NSCLC cells' proliferation and migration via triggering ERK1/2-cyclin D1 and PAK1-cofilin signaling, respectively. Additionally, apelin/APJ system may act as a predictor in the development of OSAS and PE. Considering the pleiotropic actions of apelin/APJ system, targeting apelin/APJ system may be a potent therapeutic avenue for respiratory diseases.
Subject(s)
Apelin Receptors/metabolism , Apelin/metabolism , Lung Diseases/pathology , Lung Neoplasms/pathology , Apelin/agonists , Apelin/antagonists & inhibitors , Apelin Receptors/agonists , Apelin Receptors/antagonists & inhibitors , Humans , Lung Diseases/metabolism , Lung Neoplasms/metabolism , MicroRNAs/metabolism , NF-kappa B/metabolism , Oxidoreductases/metabolism , Protein Kinases/metabolism , Signal TransductionABSTRACT
To fight against metabolic disorders such as insulin resistance, new alimentary behaviors are developed. For instance, hyperproteined, gluten-free, or collagen-enriched diets could be preconized in order to reduce the consequences of obesity. In this aim, this study evaluates the potential effects of warm sea fish collagen peptides (Naticol®) on representative metabolic and inflammatory parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat diet (HFD) were submitted or not to specific collagen peptides in drinking water (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and insulin sensitivity were followed up. Effects of fish collagen peptides on various blood parameters reflecting the metabolism status were also measured (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte inflammation. Results showed that HFD-fed mice supplemented by fish collagen peptides exhibited a significant lower increase in body weight as soon as the twelfth week of treatment whereas no effect of the peptide was observed in CD fed mice. In line with this result, a weaker increase in fat mass in HFD-fed mice supplemented with Naticol® at both 9 and 18 weeks of treatment was also observed. In spite of this resistance to obesity promoted by fish collagen peptides treatment, no difference in glucose tolerance was found between groups whereas mice treated with Naticol® exhibited a lower basal glycemia. Also, even if no effect of the treatment on adipocyte lipolysis was found, a decrease of inflammatory cytokines was retrieved in collagen-supplemented group arguing for a potential better insulin sensitivity. Altogether, these results need to be completed but are the first describing a benefic role of warm sea fish collagen peptides in a context of metabolic disease paving the route for a potential utilization in human obesity-associated disorders.
Subject(s)
Anti-Obesity Agents/therapeutic use , Collagen/therapeutic use , Dietary Supplements , Fish Proteins, Dietary/therapeutic use , Insulin Resistance , Obesity/therapy , Peptide Fragments/therapeutic use , Adipose Tissue/immunology , Adipose Tissue/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Obesity Agents/adverse effects , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/metabolism , Apelin/agonists , Apelin/genetics , Apelin/metabolism , Collagen/adverse effects , Collagen/chemistry , Collagen/metabolism , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/metabolism , Diet, High-Fat/adverse effects , Dietary Supplements/adverse effects , Fish Proteins, Dietary/adverse effects , Fish Proteins, Dietary/chemistry , Fish Proteins, Dietary/metabolism , Gene Expression Regulation , Glucose Intolerance/etiology , Glucose Intolerance/immunology , Glucose Intolerance/prevention & control , Lipolysis , Male , Mice, Inbred C57BL , Obesity/etiology , Obesity/metabolism , Obesity/physiopathology , Panniculitis/etiology , Panniculitis/immunology , Panniculitis/prevention & control , Peptide Fragments/adverse effects , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Weight GainABSTRACT
BACKGROUND: Global burden of cardiometabolic disease warrants development of newer treatment strategies. Apelin is ubiquitously expressed endogenous peptide which is a ligand for the apelinergic (APJ) receptor. Apelin/APJ receptors regulate a variety of biological functions and have been implicated in cardiovascular and metabolic homeostasis. Consequently, the apelinergic pathway represents an attractive target to treat conditions associated with cardiometabolic syndrome. OBJECTIVE: This review highlights the important regulatory role played by apelin in energy metabolism and cardiovascular function, and potential avenues that could be harnessed for therapeutic benefit. CONCLUSION: Apelin/APJ system is a druggable target to treat or prevent a variety of cardiometabolic diseases.
Subject(s)
Cardiovascular Diseases/drug therapy , Metabolic Diseases/drug therapy , Animals , Apelin/agonists , Apelin/metabolism , Apelin Receptors/agonists , Apelin Receptors/metabolism , Cardiovascular Diseases/metabolism , Energy Metabolism/drug effects , Humans , Lipid Metabolism , Metabolic Diseases/metabolism , Molecular Targeted Therapy , Signal Transduction/drug effectsABSTRACT
The apelin/apelin receptor system is widely distributed and has a dominant role in cardiovascular homeostasis and disease. The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is subsequently cleaved to generate a family of apelin peptides that possess similar functions but display different tissue distribution, potency and receptor binding affinity. Loss-of-function experiments using the apelin and the apelin receptor knockout mice and gain-of-function experiments using apelin peptides have delineated a well-defined role of the apelin axis in cardiovascular physiology and diseases. Activation of the apelin receptor by its cognate peptide ligand, apelin, induces a wide range of physiological effects, including vasodilation, increased myocardial contractility, angiogenesis, and balanced energy metabolism and fluid homeostasis. The apelin/apelin receptor pathway is also implicated in atherosclerosis, hypertension, coronary artery disease, heart failure, diabetes and obesity, making it a promising therapeutic target. Hence, research is expanding to develop novel therapies that inhibit degradation of endogenous apelin peptides or their analogues. Chemical synthesis of stable apelin receptor agonists aims to more efficiently enhance the activation of the apelin system. Targeting the apelin/apelin receptor axis has emerged as a novel therapeutic approach against cardiovascular diseases and an increased understanding of cardiovascular actions of the apelin system will help to develop effective interventions.
Subject(s)
Apelin Receptors , Apelin , Cardiovascular Diseases , Signal Transduction , Animals , Apelin/agonists , Apelin/antagonists & inhibitors , Apelin/genetics , Apelin/metabolism , Apelin Receptors/agonists , Apelin Receptors/antagonists & inhibitors , Apelin Receptors/genetics , Apelin Receptors/metabolism , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Energy Metabolism , Humans , Mice , Mice, Knockout , Myocardial Contraction , Neovascularization, PhysiologicABSTRACT
The G-protein-coupled receptor APJ and its endogenous ligand apelin are widely expressed in many peripheral tissues and central nervous system, including adipose tissue, skeletal muscles and hypothalamus. Apelin/APJ system, involved in numerous physiological functions like angiogenesis, fluid homeostasis and energy metabolism regulation, is notably implicated in the development of different pathologies such as diabetes and its complications. Increasing evidence suggests that apelin regulates insulin sensitivity, stimulates glucose utilization and enhances brown adipogenesis in different tissues associated with diabetes. Moreover, apelin is also involved in the regulation of diabetic complications via binding to APJ receptor. Apelin improves diabetes-induced kidney hypertrophia, normalizes obesity-associated cardiac hypertrophy and negatively promotes retinal angiogenesis in diabetic retinopathy. In this review, we provide a comprehensive overview about the role of apelin/APJ system in different tissues related with diabetes. Furthermore, we describe the pathogenesis of diabetic complications associated with apelin/APJ system. Finally, agonists and antagonists targeted to APJ receptor are described in the literature. Thus, we highlight apelin/APJ system as a novel therapeutic target for pharmacological intervention in treating diabetes and its complications.
