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Neural Plasticity 2018Adiponectin, the most abundant plasma adipokine, plays an important role in the regulation of glucose and lipid metabolism. Adiponectin also possesses... (Review)
Review
Adiponectin, the most abundant plasma adipokine, plays an important role in the regulation of glucose and lipid metabolism. Adiponectin also possesses insulin-sensitizing, anti-inflammatory, angiogenic, and vasodilatory properties which may influence central nervous system (CNS) disorders. Although initially not thought to cross the blood-brain barrier, adiponectin enters the brain through peripheral circulation. In the brain, adiponectin signaling through its receptors, AdipoR1 and AdipoR2, directly influences important brain functions such as energy homeostasis, hippocampal neurogenesis, and synaptic plasticity. Overall, based on its central and peripheral actions, recent evidence indicates that adiponectin has neuroprotective, antiatherogenic, and antidepressant effects. However, these findings are not without controversy as human observational studies report differing correlations between plasma adiponectin levels and incidence of CNS disorders. Despite these controversies, adiponectin is gaining attention as a potential therapeutic target for diverse CNS disorders, such as stroke, Alzheimer's disease, anxiety, and depression. Evidence regarding the emerging role for adiponectin in these disorders is discussed in the current review.
Topics: Adiponectin; Animals; Brain; Central Nervous System Diseases; Humans; Receptors, Adiponectin; Signal Transduction
PubMed: 30150999
DOI: 10.1155/2018/4593530 -
International Journal of Epidemiology Aug 2014We conducted a meta-analysis in order to investigate whether circulating adiponectin, an insulin-sensitizing hormone produced by adipocytes, is associated with breast... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We conducted a meta-analysis in order to investigate whether circulating adiponectin, an insulin-sensitizing hormone produced by adipocytes, is associated with breast cancer risk.
METHODS
A systematic literature search was performed in PubMed, Medline, EMBASE, ISI Web of Knowledge and the Cochrane Library. The summary relative risk (SRR) was calculated by pooling the different study-specific estimates using the random effect models. Meta-regression, subgroup and sensitivity analyses were carried out to investigate between-study heterogeneity and to test publication bias.
RESULTS
Data from 15 observational studies, published between 2003 and April 2013 for a total of 4249 breast cancer cases, were analysed. The SRR for the 'highest' vs 'lowest' adiponectin levels indicated a 34% reduction in breast cancer risk [95% confidence interval (CI): 13%-50%]. Between-study heterogeneity was not substantial (I(2)=53%). Ten studies were included in the dose-response analysis: the SRR for an increase of 3 µg/ml of adiponectin corresponded to a 5% risk reduction (95% CI: 1%-9%). The comparison between 'highest' and 'lowest' levels of adiponectin showed an inverse association in postmenopausal women (SRR=0.80; 95% CI: 0.63-1.01) and an indication of an inverse relationship in premenopausal women (SRR=0.72, 95% CI: 0.30-1.72). No evidence of publication bias was found.
CONCLUSIONS
Low circulating adiponectin levels are associated with an increased breast cancer risk. However, properly designed studies are needed to confirm the role of adiponectin as breast cancer biomarker, and clinical trials should be performed to identify those interventions that may be effective in modulating adiponectin levels and reducing breast cancer risk.
Topics: Adiponectin; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Risk
PubMed: 24737805
DOI: 10.1093/ije/dyu088 -
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 -
Medicine Jul 2018Accumulating data have found that adiponectin is involved in development of breast cancer (BC). However, these results were inconsistent. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating data have found that adiponectin is involved in development of breast cancer (BC). However, these results were inconsistent.
METHOD
A systematic search in PubMed, Embase, ISI Web of Science, and Chinese National Knowledge Infrastructure databases were conducted up to October 1, 2017. The standardized mean difference (SMD) with 95% confidence interval was applied to pool the effect size.
RESULTS
Finally, 31 eligible studies were included in this meta-analysis. The overall results indicated that serum adiponectin levels in BC cases were significantly lower than the controls (SMD = -0.33, P < 0.0001). As for the subgroup analysis of menstrual status, serum adiponectin levels were significantly lower in pre- and postmenopausal BC cases. Moreover, the subgroup analysis by ethnicity in pre- and postmenopausal group indicated an inverse association between adiponectin levels and BC risk in Asian population, but not in Caucasian population.
CONCLUSION
The present meta-analysis suggests that low serum adiponectin concentration may be associated with an increased BC risk in premenopausal and postmenopausal women, especially among Asians. Adiponectin may serve as a biomarker of BC risk and help to identify subjects at high risk for BC development.
Topics: Adiponectin; Biomarkers; Breast Neoplasms; Female; Humans; Risk Factors
PubMed: 30024516
DOI: 10.1097/MD.0000000000011433 -
Lipids in Health and Disease Aug 2018The objective of this study was to perform a meta-analysis to investigate the specific relationship between the expression level of circulating adiponectin and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The objective of this study was to perform a meta-analysis to investigate the specific relationship between the expression level of circulating adiponectin and osteoarthritis (OA).
METHOD
Multiple databases were searched to estimate the high quality of studies relevant to adiponectin and OA. We extracted the data from the eligible studies and included them in the meta-analysis using a random effects model. Subgroup analysis and meta-regression were further performed to explore the potential sources of heterogeneity.
RESULTS
Ten articles consisting of thirteen case-control studies that contained a combined total of 1255 subjects. Our results revealed that the OA patients displayed higher adiponectin levels than the healthy controls (SMD = 0.327, 95% CI: 0.11-0.55, P = 0.003). The ethnicity-stratified subgroup analysis indicated that the adiponectin was a sensitive biomarker in both Caucasians (P = 0.021) and Asians (P = 0.037). Moreover, the meta-regression analysis suggested that the sample size (P = 0.03) and nationality (p = 0.01) could account for a part of heterogeneity in our study.
CONCLUSION
Taken together, the current study indicated that the adiponectin expression levels were higher in the OA patients than in the healthy controls and might be associated with OA prevalence.
Topics: Adiponectin; Adult; Aged; Female; Humans; Male; Middle Aged; Multivariate Analysis; Osteoarthritis; Publication Bias
PubMed: 30115130
DOI: 10.1186/s12944-018-0838-x -
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 -
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 -
Adipocyte Dec 2023Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been...
Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been established. In this study, we employed an integrative analysis that combined Mendelian randomization (MR) and bioinformatics analyses to comprehensively explore the association between DR and adiponectin, aiming to provide a unified answer of their relationship. Using the inverse-variance weighted (IVW) method, the odd ratio (OR) of developing DR per 1 mg/dL increment in genetically predicted log-transformed adiponectin concentration was estimated to be 0.949 ( = 0.557). Other robust MR methods produced consistent results, confirming the absence of a causal effect of adiponectin on DR. Additionally, the expression levels of the six adiponectin-related genes showed no significant differences among normal controls, individuals with diabetes but without DR, and those with DR Furthermore, the biological pathways enriched by these genes were not strongly relevant to DR. At both the individual gene and pathway levels, there were no overlaps between the adiponectin-related genes and the differentially expressed genes, indicating a lack of association between adiponectin and DR based on gene expression profiles. In summary, the integrative analysis, which combined MR and bioinformatics data mining, yielded compelling evidence supporting the notion that adiponectin is not a risk factor for DR.
Topics: Humans; Diabetic Retinopathy; Adiponectin; Transcriptome; Mendelian Randomization Analysis; Risk Factors; Diabetes Mellitus
PubMed: 37459460
DOI: 10.1080/21623945.2023.2234522