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International Journal of Molecular... Jun 2017Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2... (Review)
Review
Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review.
Topics: Adiponectin; Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium; Humans; Insulin Resistance; Models, Molecular; Molecular Targeted Therapy; Obesity; Signal Transduction
PubMed: 28635626
DOI: 10.3390/ijms18061321 -
Nature Metabolism Mar 2019Adiponectin is one of the most widely studied adipokines to date. First described in the mid-1990's, studying its regulation, biogenesis and physiological effects has... (Review)
Review
Adiponectin is one of the most widely studied adipokines to date. First described in the mid-1990's, studying its regulation, biogenesis and physiological effects has proven to be extremely insightful and improved our understanding of the mechanisms that ensure systemic metabolic homeostasis. Here, we provide a brief overview of the current state of the field with respect to adiponectin, its history, sites and mechanisms of action, and the critical questions that will need to be addressed in the future.
Topics: Adipocytes; Adiponectin; Animals; Biomarkers; Humans
PubMed: 32661510
DOI: 10.1038/s42255-019-0041-z -
Journal of Molecular Cell Biology Apr 2016Adiponectin is an adipocyte-specific factor, first described in 1995. Over the past two decades, numerous studies have elucidated the physiological functions of... (Review)
Review
Adiponectin is an adipocyte-specific factor, first described in 1995. Over the past two decades, numerous studies have elucidated the physiological functions of adiponectin in obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Adiponectin, elicited through cognate receptors, suppresses glucose production in the liver and enhances fatty acid oxidation in skeletal muscle, which together contribute to a beneficial metabolic action in whole body energy homeostasis. Beyond its role in metabolism, adiponectin also protects cells from apoptosis and reduces inflammation in various cell types via receptor-dependent mechanisms. Adiponectin, as a fat-derived hormone, therefore fulfills a critical role as an important messenger to communicate between adipose tissue and other organs. A better understanding of adiponectin actions, including the pros and cons, will advance our insights into basic mechanisms of metabolism and inflammation, and potentially pave the way toward novel means of pharmacological intervention to address pathophysiological changes associated with diabetes, atherosclerosis, and cardiometabolic disease.
Topics: Adiponectin; Animals; Cells; Humans; Models, Molecular; Receptors, Adiponectin
PubMed: 26993047
DOI: 10.1093/jmcb/mjw011 -
International Journal of Molecular... Feb 2020Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular,... (Review)
Review
Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular, middle-molecular, and low-molecular weight isoforms. Numerous studies have demonstrated its insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. Additionally, decreased serum levels of adiponectin is associated with chronic inflammation of metabolic disorders including Type 2 diabetes, obesity, and atherosclerosis. However, recent studies showed that adiponectin could have pro-inflammatory roles in patients with autoimmune diseases. In particular, its high serum level was positively associated with inflammation severity and pathological progression in rheumatoid arthritis, chronic kidney disease, and inflammatory bowel disease. Thus, adiponectin seems to have both pro-inflammatory and anti-inflammatory effects. This indirectly indicates that adiponectin has different physiological roles according to an isoform and effector tissue. Knowledge on the specific functions of isoforms would help develop potential anti-inflammatory therapeutics to target specific adiponectin isoforms against metabolic disorders and autoimmune diseases. This review summarizes the current roles of adiponectin in metabolic disorders and autoimmune diseases.
Topics: Adaptor Proteins, Signal Transducing; Adiponectin; Adipose Tissue, White; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Atherosclerosis; Autoimmune Diseases; Diabetes Mellitus, Type 2; Disease; Humans; Inflammation; Inflammatory Bowel Diseases; Obesity; Protein Isoforms; Renal Insufficiency, Chronic
PubMed: 32059381
DOI: 10.3390/ijms21041219 -
International Journal of Molecular... Mar 2019In skeletal muscle, adiponectin has varied and pleiotropic functions, ranging from metabolic, anti-inflammatory, insulin-sensitizing to regenerative roles. Despite the... (Review)
Review
In skeletal muscle, adiponectin has varied and pleiotropic functions, ranging from metabolic, anti-inflammatory, insulin-sensitizing to regenerative roles. Despite the important functions exerted by adiponectin, the study of the hormone in myopathies is still marginal. Myopathies include inherited and non-inherited/acquired neuromuscular pathologies characterized by muscular degeneration and weakness. This review reports current knowledge about adiponectin in myopathies, regarding in particular the role of adiponectin in some hereditary myopathies (as Duchenne muscular dystrophy) and non-inherited/acquired myopathies (such as idiopathic inflammatory myopathies and fibromyalgia). These studies show that some myopathies are characterized by decreased concentration of plasma adiponectin and that hormone replenishment induces beneficial effects in the diseased muscles. Overall, these findings suggest that adiponectin could constitute a future new therapeutic approach for the improvement of the abnormalities caused by myopathies.
Topics: Adiponectin; Animals; Humans; Inheritance Patterns; Muscle, Skeletal; Muscular Diseases
PubMed: 30934785
DOI: 10.3390/ijms20071544 -
Molecular Therapy : the Journal of the... Oct 2020Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that originally reside in virtually all tissues, and the gain of MSCs by transplantation has become...
Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that originally reside in virtually all tissues, and the gain of MSCs by transplantation has become the leading form of cell therapy in various diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients. Here, we report that the cardioprotective properties of intravenously injected MSCs in a mouse model of pressure-overload heart failure largely depend on circulating adiponectin, an adipocyte-secreted factor. The injected MSCs exert their function through exosomes, extracellular vesicles of endosome origin. Adiponectin stimulated exosome biogenesis and secretion through binding to T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin, on MSCs. A pharmacological or adenovirus-mediated genetic increase in plasma adiponectin enhanced the therapeutic efficacy of MSCs. Our findings provide novel insights into the importance of adiponectin in mesenchymal-progenitor-mediated organ protections.
Topics: Adiponectin; Animals; Cadherins; Cells, Cultured; Disease Models, Animal; Disease Susceptibility; Exosomes; Extracellular Vesicles; Heart Failure; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice
PubMed: 32652045
DOI: 10.1016/j.ymthe.2020.06.026 -
International Journal of Molecular... Aug 2021Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions.... (Review)
Review
Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.
Topics: Adipokines; Adiponectin; Asthma; Humans; Insulin Resistance; Leptin; Obesity
PubMed: 34445677
DOI: 10.3390/ijms22168971 -
International Journal of Molecular... Mar 2020Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties.... (Review)
Review
Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Initially, it was thought that the main role was only the metabolism control. Later, ADPN receptors were also found in the central nervous system (CNS). In fact, the receptors AdipoR1 and AdipoR2 are expressed in various areas of the brain, including the hypothalamus, hippocampus, and cortex. While AdipoR1 regulates insulin sensitivity through the activation of the AMP-activated protein kinase (AMPK) pathway, AdipoR2 stimulates the neural plasticity through the activation of the peroxisome proliferator-activated receptor alpha (PPARα) pathway that inhibits inflammation and oxidative stress. Overall, based on its central and peripheral actions, ADPN appears to have neuroprotective effects by reducing inflammatory markers, such as C-reactive protein (PCR), interleukin 6 (IL6), and Tumor Necrosis Factor a (TNFa). Conversely, high levels of inflammatory cascade factors appear to inhibit the production of ADPN, suggesting bidirectional modulation. In addition, ADPN appears to have insulin-sensitizing action. It is known that a reduction in insulin signaling is associated with cognitive impairment. Based on this, it is of great interest to investigate the mechanism of restoration of the insulin signal in the brain as an action of ADPN, because it is useful for testing a possible pharmacological treatment for the improvement of cognitive decline. Anyway, if ADPN regulates neuronal functioning and cognitive performances by the glycemic metabolic system remains poorly explored. Moreover, although the mechanism is still unclear, women compared to men have a doubled risk of developing cognitive decline. Several studies have also supported that during the menopausal transition, the estrogen reduction can adversely affect the brain, in particular, verbal memory and verbal fluency. During the postmenopausal period, in obese and insulin-resistant individuals, ADPN serum levels are significantly reduced. Our recent study has evaluated the relationship between plasma ADPN levels and cognitive performances in menopausal women. Thus, the aim of this review is to summarize both the mechanisms and the effects of ADPN in the central nervous system and the relationship between plasma ADPN levels and cognitive performances, also in menopausal women.
Topics: AMP-Activated Protein Kinases; Adiponectin; Adipose Tissue; Biomarkers; Brain; Central Nervous System; Cognitive Dysfunction; Dementia; Estrogens; Female; Humans; Inflammation; Insulin; Insulin Resistance; Male; Memory; Menopause; Obesity; PPAR alpha; Receptors, Adiponectin; Risk Factors; Signal Transduction; Speech Disorders
PubMed: 32188008
DOI: 10.3390/ijms21062010 -
Frontiers in Endocrinology 2020
Topics: Adiponectin; Animals; Drug Development; Humans
PubMed: 32547493
DOI: 10.3389/fendo.2020.00343 -
Reviews in Endocrine & Metabolic... Jun 2014White adipose tissue (WAT) is the premier energy depot. Since the discovery of the hormonal properties of adipose-secreted proteins such as leptin and adiponectin, WAT... (Review)
Review
White adipose tissue (WAT) is the premier energy depot. Since the discovery of the hormonal properties of adipose-secreted proteins such as leptin and adiponectin, WAT has been classified as an endocrine organ. Although many regulatory effects of the adipocyte-derived hormones on various biological systems have been identified, maintaining systemic energy homeostasis is still the essential function of most adipocyte-derived hormones. Adiponectin is one adipocyte-derived hormone and well known for its effect in improving insulin sensitivity in liver and skeletal muscle. Unlike most other adipocyte-derived hormones, adiponectin gene expression and blood concentration are inversely associated with adiposity. Interestingly, recent studies have demonstrated that, in addition to its insulin sensitizing effects, adiponectin plays an important role in maintaining energy homeostasis. In this review, we summarize the progress of research about 1) the causal relationship of adiposity, energy intake, and adiponectin gene expression; and 2) the regulatory role of adiponectin in systemic energy metabolism.
Topics: Adiponectin; Adipose Tissue, White; Adiposity; Energy Metabolism; Gene Expression Regulation; Homeostasis; Humans; Insulin Resistance
PubMed: 24170312
DOI: 10.1007/s11154-013-9283-3