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Journal of Molecular Cell Biology Apr 2016Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of... (Review)
Review
Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of life. Despite great progress made towards a better understanding of the molecular basis of diabetes, the available clinical counter-measures against insulin resistance, a defect that is central to obesity-linked type 2 diabetes, remain inadequate. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in major insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism. However, adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention, and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation, and reveal therapeutic targets. Here, we discuss tissue- and cell-specific functions of adiponectin, with an emphasis on the regulation of adiponectin signaling pathways, and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation. Understanding better just why and how adiponectin and its downstream effector molecules work will be essential, together with empirical trials, to guide us to therapies that target the root cause(s) of type 2 diabetes and insulin resistance.
Topics: Adiponectin; Animals; Humans; Insulin; Models, Biological; Organ Specificity; Receptors, Adiponectin; Signal Transduction
PubMed: 26993044
DOI: 10.1093/jmcb/mjw014 -
Revista Da Associacao Medica Brasileira... 2015the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent... (Review)
Review
OBJECTIVES
the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent studies strongly indicate that adipose tissue is an active endocrine organ that secretes bioactive factors such as adipokines. Adiponectin appears to have a regulatory role in the mechanism of insulin resistance and in the development of atherosclerosis. This systematic review aims to evaluate the anti-atherogenic effects of adiponectin and its properties to improve and mimic metabolic and vascular actions of insulin and its influence on endothelial function.
METHODS
a qualitative, exploratory and literature review was performed in the PubMed, Portal Capes and Scielo databases using as key-words "adiponectin", "obesity", "insulin resistance", "anti-inflammatory", "therapeutic strategies" and "future prospects".
RESULTS
evidence suggests that adiponectin has anti-atherogenic properties with anti-inflammatory effects on the vascular wall. Moreover, it modifies the vascular intracellular signaling and has indirect antioxidant effects on the human myocardium. On the other hand, there are studies suggesting that increased levels of adiponectin are paradoxically associated with a worse prognosis in heart failure syndrome, although the mechanisms are not clear.
CONCLUSION
it is not clear whether adiponectin levels have any clinical significance for risk stratification in cardiovascular disease or if they simply reflect the activation of complex underlying mechanisms. Changes in lifestyle and some drug treatments for hypertension and coronary heart disease have shown significant effect to increase adiponectin levels, and simultaneously decrease in insulin resistance and endothelial dysfunction.
Topics: Adiponectin; Adipose Tissue; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Life Style; Male; Obesity; Receptors, Adiponectin; Risk Factors
PubMed: 25909213
DOI: 10.1590/1806-9282.61.01.072 -
International Immunopharmacology Oct 2015Adiponectin is a circulating hormone with pleiotropic functions in lipid and glucose metabolism secreted by adipocytes. It plays a beneficial role in cardiovascular... (Review)
Review
Adiponectin is a circulating hormone with pleiotropic functions in lipid and glucose metabolism secreted by adipocytes. It plays a beneficial role in cardiovascular functions and metabolic complications. Recently, growing researches have elucidated that increased adiponectin plasma levels correlate with severity of rheumatoid arthritis (RA) and it is speculative that adiponectin may link to RA. The association of adiponectin with potential inflammatory functions in RA has raised significant interests in exploring this adipokine as a target for RA-diagnostic and therapeutic applications. Despite significant advances in understanding adiponectin functions and signaling mechanisms, its roles in RA remain multifaceted and subject to controversy. This review highlights the evidences linking adiponectin to either anti-inflammatory or pro-inflammatory action in RA. The results of this review may provide important insight into adiponectin in the development of RA.
Topics: Adipocytes; Adiponectin; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Biomarkers; Glucose; Humans; Inflammation Mediators; Lipid Metabolism
PubMed: 26307192
DOI: 10.1016/j.intimp.2015.08.013 -
Metabolic Brain Disease Jan 2023Dementia, especially Alzheimer's Disease (AD) and vascular dementia, is a major public health problem that continues to expand in both economically emerging and... (Review)
Review
Dementia, especially Alzheimer's Disease (AD) and vascular dementia, is a major public health problem that continues to expand in both economically emerging and hegemonic countries. In 2017, the World Alzheimer Report estimated that over 50 million people were living with dementia globally. Metabolic dysfunctions of brain structures such as the hippocampus and cerebral cortex have been implicated as risk factors for dementia. Several well-defined metabolic risk factors for AD include visceral obesity, chronic inflammation, peripheral and brain insulin resistance, type 2 diabetes mellitus (T2DM), hypercholesterolemia, and others. In this review, we describe the relationship between the dysmetabolic mechanisms, although still unknown, and dementia, particularly AD. Adiponectin (ADPN), the most abundant circulating adipocytokine, acts as a protagonist in the metabolic dysfunction associated with AD, with unexpected and intriguing dual biological functions. This contradictory role of ADPN has been termed the adiponectin paradox. Some evidence suggests that the adiponectin paradox is important in amyloidogenic evolvability in AD. We present cumulative evidence showing that AD and T2DM share many common features. We also review the mechanistic pathways involving brain insulin resistance. We discuss the importance of the evolvability of amyloidogenic proteins (APs), defined as the capacity of a system for adaptive evolution. Finally, we describe potential therapeutic strategies in AD, based on the adiponectin paradox.
Topics: Humans; Alzheimer Disease; Adiponectin; Insulin Resistance; Diabetes Mellitus, Type 2; Brain
PubMed: 35921057
DOI: 10.1007/s11011-022-01064-8 -
The Korean Journal of Internal Medicine May 2019The metabolic burden caused by hyperglycemia can result in direct and immediate metabolic injuries, such as oxidative stress and tissue inflammation, in the kidney.... (Review)
Review
The metabolic burden caused by hyperglycemia can result in direct and immediate metabolic injuries, such as oxidative stress and tissue inflammation, in the kidney. Furthermore, chronic hyperglycemia can lead to substantial structural changes such as formation of advanced glycation end-products, glomerular and tubular hypertrophy, and tissue fibrosis. Glomerular hypertrophy renders podocytes vulnerable to increased glomerular filtration, leading to podocyte instability and loss. Thus, prevention of glomerular hypertrophy and attenuation of glomerular hyperfiltration may have therapeutic potential for diabetic nephropathy (DN). Adiponectin is an adipokine that improves insulin sensitivity in obesity-related metabolic disorders, including diabetes, but its efficacy is unknown. Moreover, the recently developed adiponectin receptor agonist, AdipoRon, shows therapeutic potential for DN. In this review, we focus on the role of glomerular hypertrophy in the pathogenesis of DN and discuss the role of adiponectin in its prevention.
Topics: Adiponectin; Adipose Tissue; Animals; Diabetic Nephropathies; Humans; Hypertrophy; Insulin; Insulin Resistance; Kidney Glomerulus; Signal Transduction
PubMed: 31048658
DOI: 10.3904/kjim.2019.109 -
Metabolic Brain Disease Oct 2021Obesity and dementia are two growing problems worldwide. Obesity act as a crucial risk factor for various diseases including Alzheimer's disease (AD). Several... (Review)
Review
Obesity and dementia are two growing problems worldwide. Obesity act as a crucial risk factor for various diseases including Alzheimer's disease (AD). Several preclinical studies showed that middle-age obesity can be act as a possible feature of mild cognitive impairment in later years. Some studies have also demonstrated that a high-fat diet causes AD pathology, including extracellular amyloid-beta accumulation, hyperphosphorylation of tau, and cognition impairment. The correlation and molecular mechanism related to obesity-associated AD needs to be better evaluated. Presently, obesity results in an altered expression of several hormones, growth factors, and adipokines. Multiple signaling pathways such as leptin, insulin, adiponectin, and glutamate are involved to regulate vital functions in the brain and act as neuroprotective mediators for AD in a normal state. In obesity, altered adiponectin (APN) level and its associated downstream pathway could result in multiple signaling pathway disruption. Presently, Adiponectin and its inducers or agonist are considered as potential therapeutics for obesity-associated AD. This review mainly focuses on the pleiotropic effects of adiponectin and its potential to treat obesity-associated AD.
Topics: Adiponectin; Alzheimer Disease; Animals; Humans; Insulin; Leptin; Obesity; Signal Transduction
PubMed: 34047927
DOI: 10.1007/s11011-021-00756-x -
Cardiovascular Drugs and Therapy Dec 2016Adiponectin is the most abundant adipokine and exhibits anti-inflammatory, antiatherogenic and antidiabetic properties. Unlike other adipokines, it inversely correlates... (Review)
Review
Adiponectin is the most abundant adipokine and exhibits anti-inflammatory, antiatherogenic and antidiabetic properties. Unlike other adipokines, it inversely correlates with body weight and obesity-linked cardiovascular complications. Diastolic dysfunction is the main mechanism responsible for approximately half of all heart failure cases, the so-called heart failure with preserved ejection fraction (HFpEF), but therapeutic strategies specifically directed towards these patients are still lacking. In the last years, a link between adiponectin and diastolic dysfunction has been suggested. There are several mechanisms through which adiponectin may prevent most of the pathophysiologic mechanisms underlying diastolic dysfunction and HFpEF, including the prevention of myocardial hypertrophy, cardiac fibrosis, nitrative and oxidative stress, atherosclerosis and inflammation, while promoting angiogenesis. Thus, understanding the mechanisms underlying adiponectin-mediated improvement of diastolic function has become an exciting field of research, making adiponectin a promising therapeutic target. In this review, we explore the relevance of adiponectin signaling for the prevention of diastolic dysfunction and identify prospective therapeutic targets aiming at the treatment of this clinical condition.
Topics: Adiponectin; Animals; Atherosclerosis; Diastole; Heart Diseases; Humans; Neovascularization, Physiologic; Oxidative Stress
PubMed: 27757724
DOI: 10.1007/s10557-016-6694-x -
Molecular Genetics and Metabolism Nov 2014The knowledge of the pathogenesis of obesity and its metabolic sequelae has significantly advanced over the last few decades and adipose tissue is now considered a link... (Review)
Review
The knowledge of the pathogenesis of obesity and its metabolic sequelae has significantly advanced over the last few decades and adipose tissue is now considered a link between obesity and insulin resistance. Adiponectin, one of the major adipocyte-secreted proteins, has attracted scientific interest in recent years and has been extensively studied both in human and animal models. Adiponectin exerts insulin-sensitizing effects through binding to its receptors, leading to activation of AMPK, PPAR-α, and potentially other unknown molecular pathways. In obesity-linked insulin resistance, both adiponectin and adiponectin receptors are downregulated, leading to activation of signaling pathways involved in metabolism regulation. Up-regulation of adiponectin/adiponectin receptors or enhancing adiponectin receptor function may be an interesting therapeutic strategy for obesity-linked insulin resistance. In this review we will focus on the recent research related to the relationship between the adiponectin system and insulin resistance. The potential use of adiponectin or its receptor for therapeutic intervention will be also discussed.
Topics: Adiponectin; Animals; Cell Communication; Humans; Insulin Resistance; Receptors, Adiponectin
PubMed: 25242063
DOI: 10.1016/j.ymgme.2014.09.003 -
Trends in Cardiovascular Medicine Nov 2014Adiponectin exerts both vasodilatory and insulin-sensitizing actions and its levels are decreased in insulin-resistant humans and animals. The mechanisms underlying... (Review)
Review
Adiponectin exerts both vasodilatory and insulin-sensitizing actions and its levels are decreased in insulin-resistant humans and animals. The mechanisms underlying adiponectin׳s insulin-sensitizing effect have been extensively investigated but remain largely unclear. Muscle microvasculature critically regulates muscle insulin action by modulating insulin delivery to the microvessels nurturing the muscle cells and the trans-endothelial insulin transport. We have recently reported that adiponectin exerts its insulin-sensitizing effect via recruiting muscle microvasculature, expanding the endothelial surface area, and increasing insulin delivery to and thus action in muscle. The current review focuses on the microvascular connection between the adiponectin and insulin cross talk.
Topics: Adiponectin; Blood Vessels; Humans; Insulin; Insulin Resistance; Receptor Cross-Talk
PubMed: 25220977
DOI: 10.1016/j.tcm.2014.08.001 -
Cells Jun 2021Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the... (Review)
Review
Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin's structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.
Topics: Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Blood Vessels; Endothelial Cells; Homeostasis; Humans; Muscle, Smooth, Vascular
PubMed: 34204799
DOI: 10.3390/cells10061485