-
Comprehensive Physiology Jun 2018Adipose tissue is now recognized as an important endocrine organ, capable of secreting a large number of endocrine factors which regulate a wide variety of physiological... (Review)
Review
Adipose tissue is now recognized as an important endocrine organ, capable of secreting a large number of endocrine factors which regulate a wide variety of physiological functions. Adiponectin is one such factor, secreted in large quantities primarily from adipose tissue. Adiponectin is posttranslationally modified from a 30-kDa monomeric protein into different multimers (low molecular weight or trimer, middle molecular weight or hexamer, and high molecular weight) and secreted into the circulation. Upon binding to its receptors, AdipoR1 and R2, adiponectin initiates a series of tissue-dependent signal transduction events, including phosphorylation of adenosine monophosphate (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK), and increased peroxisome proliferator-activated receptor alpha (PPARα) ligand activity. These signal transduction events are regulated by adaptor protein containing a pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPL1), which binds directly to the intracellular regions of AdipoR1 and R2. AdipoR1 and R2 also possesses inherent ceramidase activity, resulting in a decrease in intracellular ceramide, a sphingolipid that has been implicated in insulin resistance, cell death, inflammation, and atherosclerosis. Adiponectin stimulates fatty acid oxidation in skeletal muscle and inhibits glucose production in the liver, resulting in an improvement in whole-body energy homeostasis. Adiponectin is also a classic anti-inflammatory agent, reducing inflammation in various cell types through AdipoR1 and R2 signaling mechanisms. Adiponectin's anti-inflammatory and anti-apoptotic properties results in protection of the vasculature, heart, lung, and colon. In this review, we provide a comprehensive overview of the discovery, protein structure, receptors, expression, regulation, and physiological functions of adiponectin. © 2017 American Physiological Society. Compr Physiol 8:1031-1063, 2018.
Topics: Adiponectin; Adipose Tissue; Animals; Gene Expression Regulation; Humans; Protein Conformation; Receptors, Adiponectin
PubMed: 29978896
DOI: 10.1002/cphy.c170046 -
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... 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 -
Clinica Chimica Acta; International... Feb 2013Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in... (Review)
Review
Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in which insulin action is impaired in adipose tissue and is more strongly linked to intra-abdominal fat than to fat in other depots. The expression of adiponectin decreases with increase in the adiposity. Adiponectin mediates insulin-sensitizing effect through binding to its receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase (AMPK), PPAR-α, and presumably other yet-unknown signalling pathways. Weight loss significantly elevates plasma adiponectin levels. Reduction of adiponectin has been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. The other major adipokine is leptin. Leptin levels increase in obesity and subcutaneous fat has been a major determinant of circulating leptin levels. The leptin signal is transmitted by the Janus kinase, signal transducer and activator of transcription ((JAK-STAT) pathway. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight and fat.
Topics: Adiponectin; Adipose Tissue; Humans; Insulin Resistance; Leptin
PubMed: 23266767
DOI: 10.1016/j.cca.2012.12.007 -
International Review of Neurobiology 2019Adiponectin, one kind of adipokines, has been shown to be neuroprotective in different neurodegenerative diseases. Adiponectin exerts its role through combination with... (Review)
Review
Adiponectin, one kind of adipokines, has been shown to be neuroprotective in different neurodegenerative diseases. Adiponectin exerts its role through combination with its receptors and activates downstream molecular pathways. In the retinas, the expression of adiponectin can be detected and adiponectin receptors (AdipoRs) locate in different retinal cells. Adiponectin is mainly produced by adipose tissue, enters the circulation and passes through blood-brain barrier (BBB) without injury. It can also be produced locally in the brains as well as in the retinas. Therefore, it is possible that adiponectin from blood as well as that produced locally in the retinas take part in defense of different eye diseases. Here we have summarized the published data about the protective effects of adiponectin in eye diseases. Because exercise can increase the production of adiponectin systemically in the whole body and locally in the brain although no evidence has shown that exercise can increase the production of adiponectin in the eyes until now, we hypothesize that exercise will have a potential protective effect for the eyes via increasing the levels of adiponectin which needs further investigation.
Topics: Adiponectin; Animals; Exercise Therapy; Eye Diseases; Humans; Neuroprotective Agents; Receptors, Adiponectin; Retina
PubMed: 31607358
DOI: 10.1016/bs.irn.2019.07.006 -
International Journal of Molecular... Apr 2021Deregulation of adiponectin is found in systemic autoimmune rheumatic diseases (SARDs). Its expression is downregulated by various inflammatory mediators, but... (Review)
Review
Deregulation of adiponectin is found in systemic autoimmune rheumatic diseases (SARDs). Its expression is downregulated by various inflammatory mediators, but paradoxically, elevated serum levels are present in SARDs with high inflammatory components, such as rheumatoid arthritis and systemic lupus erythematosus. Circulating adiponectin is positively associated with radiographic progression in rheumatoid arthritis as well as with cardiovascular risks and lupus nephritis in systemic lupus erythematosus. However, in SARDs with less prominent inflammation, such as systemic sclerosis, adiponectin levels are low and correlate negatively with disease activity. Regulators of adiponectin gene expression (PPAR-γ, Id3, ATF3, and SIRT1) and inflammatory cytokines (interleukin 6 and tumor necrosis factor α) are differentially expressed in SARDs and could therefore influence total adiponectin levels. In addition, anti-inflammatory therapy could also have an impact, as tocilizumab treatment is associated with increased serum adiponectin. However, anti-tumor necrosis factor α treatment does not seem to affect its levels. Our review provides an overview of studies on adiponectin levels in the bloodstream and other biological samples from SARD patients and presents some possible explanations why adiponectin is deregulated in the context of therapy and gene regulation.
Topics: Adiponectin; Animals; Autoimmune Diseases; Cytokines; Humans; Models, Biological; Rheumatic Diseases; Transcription Factors
PubMed: 33920997
DOI: 10.3390/ijms22084095 -
Lipids in Health and Disease Aug 2021Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by abnormal T cell activation and excessive proliferation of keratinocytes. In addition... (Review)
Review
Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by abnormal T cell activation and excessive proliferation of keratinocytes. In addition to skin manifestations, psoriasis has been associated with multiple metabolic comorbidities, such as obesity, insulin resistance, and diabetes. An increasing amount of evidence has highlighted the core role of adipokines in adipose tissue and the immune system. This review focus on the role of adiponectin in the pathophysiology of psoriasis and its comorbidities, highlighting the future research avenues.
Topics: Adiponectin; Humans; Psoriasis
PubMed: 34372872
DOI: 10.1186/s12944-021-01510-z -
Physiology (Bethesda, Md.) May 2021Adiponectin, an adipokine that circulates as multiple multimeric complexes at high levels in serum, has antidiabetic, anti-inflammatory, antiatherogenic, and... (Review)
Review
Adiponectin, an adipokine that circulates as multiple multimeric complexes at high levels in serum, has antidiabetic, anti-inflammatory, antiatherogenic, and cardioprotective properties. Understanding the mechanisms regulating adiponectin's physiological effects is likely to provide critical insight into the development of adiponectin-based therapeutics to treat various metabolic-related diseases. In this review, we summarize our current understanding on adiponectin action in its various target tissues and in cellular models. We also focus on recent advances in two particular regulatory aspects; namely, the regulation of adiponectin gene expression, multimerization, and secretion, as well as extravasation of circulating adiponectin to the interstitial space and its degradation. Finally, we discuss some potential therapeutic approaches using adiponectin as a target and the current challenges facing adiponectin-based therapeutic interventions.
Topics: Adiponectin; Humans
PubMed: 33904786
DOI: 10.1152/physiol.00031.2020 -
Problemy Endokrinologii Oct 2021Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to... (Review)
Review
Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called 'adiponectin paradox'. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.
Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; COVID-19; Humans
PubMed: 35018766
DOI: 10.14341/probl12827