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Scandinavian Journal of Immunology Sep 2023Adiponectin and leptin are adipokines, secreted by white adipose tissue (WAT), which play an important role in energy homeostasis. Some evidence has shown that... (Review)
Review
Adiponectin and leptin are adipokines, secreted by white adipose tissue (WAT), which play an important role in energy homeostasis. Some evidence has shown that adipokine-producing adipose cells present in the bone marrow (BM) appear to exert an influence on hematopoiesis and B cell development. Common variable immunodeficiency (CVID) is one of the most common inborn errors of immunity in humans. In CVID, numerical and/or functional defects of B cells and their precursors result in hypogammaglobulinemia, usually Immunoglobulin (Ig) A and IgG. Manifestations of CVID include immunodeficiency, autoimmunity, inflammation and lymphoproliferation, resulting in a wide range of phenotypes. How adipokines interact and influence the pathophysiology of CVID is still unclear. In this review, we seek to summarize the aspects known so far concerning the interface between adipokines, B cells and CVID. More research is needed to fully understand these interactions; this knowledge is a potential avenue for the discovery of useful biomarkers and may provide new therapeutic targets for the treatment of patients with CVID and related diseases.
Topics: Humans; Adipokines; Common Variable Immunodeficiency; B-Lymphocytes; Autoimmunity; Immunoglobulin A; Adipose Tissue
PubMed: 37873571
DOI: 10.1111/sji.13257 -
Journal of Molecular and Cellular... Sep 2023Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by...
Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury.
Topics: Animals; Mice; Adiponectin; Antagomirs; Apoptosis; Diabetes Mellitus, Experimental; Infarction; MicroRNAs; Myocardial Reperfusion Injury; Myocytes, Cardiac; Up-Regulation
PubMed: 37437402
DOI: 10.1016/j.yjmcc.2023.06.004 -
Cells Aug 2023Duchenne muscular dystrophy (DMD) is one of the most devastating myopathies, where severe inflammation exacerbates disease progression. Previously, we demonstrated that...
Duchenne muscular dystrophy (DMD) is one of the most devastating myopathies, where severe inflammation exacerbates disease progression. Previously, we demonstrated that adiponectin (ApN), a hormone with powerful pleiotropic effects, can efficiently improve the dystrophic phenotype. However, its practical therapeutic application is limited. In this study, we investigated ALY688, a small peptide ApN receptor agonist, as a potential novel treatment for DMD. Four-week-old mdx mice were subcutaneously treated for two months with ALY688 and then compared to untreated mdx and wild-type mice. In vivo and ex vivo tests were performed to assess muscle function and pathophysiology. Additionally, in vitro tests were conducted on human DMD myotubes. Our results showed that ALY688 significantly improved the physical performance of mice and exerted potent anti-inflammatory, anti-oxidative and anti-fibrotic actions on the dystrophic muscle. Additionally, ALY688 hampered myonecrosis, partly mediated by necroptosis, and enhanced the myogenic program. Some of these effects were also recapitulated in human DMD myotubes. ALY688's protective and beneficial properties were mainly mediated by the AMPK-PGC-1α axis, which led to suppression of NF-κβ and TGF-β. Our results demonstrate that an ApN mimic may be a promising and effective therapeutic prospect for a better management of DMD.
Topics: Humans; Animals; Mice; Mice, Inbred mdx; Adiponectin; Receptors, Adiponectin; Muscle Fibers, Skeletal; Fibrosis
PubMed: 37626911
DOI: 10.3390/cells12162101 -
Frontiers in Endocrinology 2023Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related...
Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related brain diseases, including Alzheimer's disease (AD). However, the underlying mechanism explaining the link between MetS and brain function is poorly understood. Among the possible mediators are several adipose-derived secreted molecules called adipokines, including adiponectin (ApN) and resistin, which have been shown to regulate brain function by modulating several metabolic processes. To investigate the impact of adipokines on MetS, we employed a diet-induced model to induce the various complications associated with MetS. For this purpose, we administered a high-fat diet (HFD) to both WT and APP/PSN1 mice at a pre-symptomatic disease stage. Our data showed that MetS causes a fast decline in cognitive performance and stimulates Aβ production in the brain. Interestingly, ApN treatment restored glucose metabolism and improved cognitive functions by 50% while decreasing the Aβ ratio by approximately 65%. In contrast, resistin exacerbated Aβ pathology, increased oxidative stress, and strongly reduced glucose metabolism. Together, our data demonstrate that ApN and resistin alterations could further contribute to AD pathology.
Topics: Animals; Mice; Metabolic Syndrome; Adiponectin; Resistin; Alzheimer Disease; Adipokines; Obesity; Glucose
PubMed: 37732123
DOI: 10.3389/fendo.2023.1237796 -
Frontiers in Endocrinology 2023In the modern era, the escalating global prevalence of obesity has profound implications on female reproductive health. Obesity, transcending mere lifestyle choices, has... (Review)
Review
In the modern era, the escalating global prevalence of obesity has profound implications on female reproductive health. Obesity, transcending mere lifestyle choices, has evolved into a complex disorder affecting physiological and metabolic functions. Concurrently, female infertility is rising as a significant global health issue. Obesity, with its extensive systemic effects, is pinpointed as a major disruptor. The convergence of these health challenges reveals a multifaceted scenario: on one hand, obesity directly impacts female reproductive health, particularly in the context of conditions like polycystic ovary syndrome (PCOS) and menstrual disturbances; on the other, the psychosocial consequences of infertility might intensify weight-gain patterns, forming a challenging cycle. Additionally, the economic implications of treating obesity-related infertility are considerable. This review delves into the myriad ways obesity affects female reproductive health, drawing insights from epidemiological, clinical, and molecular studies. It explores the epidemiological relationship between obesity and PCOS, the influence of obesity on menstrual disturbances, and the broader impact of obesity on female infertility. Weight loss, through pharmacological interventions, surgical methods, or lifestyle adjustments, emerges as a promising strategy. Lastly, the efficacy of assisted reproductive technologies, such as IVF, is influenced by obesity, underscoring the importance of an optimal body mass index. The review also highlights the molecular and physiological mechanisms underlying the impact of obesity on female reproductive health, including the disruption of the hypothalamic-pituitary-ovary axis, altered adipokine secretion, and the role of chronic inflammation and oxidative stress.
Topics: Female; Humans; Infertility, Female; Reproductive Health; Obesity; Weight Gain; Adipokines; Polycystic Ovary Syndrome
PubMed: 38264286
DOI: 10.3389/fendo.2023.1326546 -
EMBO Reports Dec 2023Chronic stress induces depression and insulin resistance, between which there is a bidirectional relationship. However, the mechanisms underlying this comorbidity remain...
Chronic stress induces depression and insulin resistance, between which there is a bidirectional relationship. However, the mechanisms underlying this comorbidity remain unclear. White adipose tissue (WAT), innervated by sympathetic nerves, serves as a central node in the interorgan crosstalk through adipokines. Abnormal secretion of adipokines is involved in mood disorders and metabolic morbidities. We describe here a brain-sympathetic nerve-adipose circuit originating in the hypothalamic paraventricular nucleus (PVN) with a role in depression and insulin resistance induced by chronic stress. PVN neurons are labelled after inoculation of pseudorabies virus (PRV) into WAT and are activated under restraint stress. Chemogenetic manipulations suggest a role for the PVN in depression and insulin resistance. Chronic stress increases the sympathetic innervation of WAT and downregulates several antidepressant and insulin-sensitizing adipokines, including leptin, adiponectin, Angptl4 and Sfrp5. Chronic activation of the PVN has similar effects. β-adrenergic receptors translate sympathetic tone into an adipose response, inducing downregulation of those adipokines and depressive-like behaviours and insulin resistance. We finally show that AP-1 has a role in the regulation of adipokine expression under chronic stress.
Topics: Rats; Animals; Paraventricular Hypothalamic Nucleus; Insulin Resistance; Rats, Sprague-Dawley; Depression; Obesity; Adipokines
PubMed: 37870400
DOI: 10.15252/embr.202357176 -
Frontiers in Endocrinology 2023
Topics: Humans; Adipokines; Leptin; Adiponectin; Metabolic Diseases
PubMed: 38027208
DOI: 10.3389/fendo.2023.1303966 -
Journal of Sports Science & Medicine Jun 2024Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of... (Meta-Analysis)
Meta-Analysis Review
Combined Aerobic and Resistance Training Improves Body Composition, Alters Cardiometabolic Risk, and Ameliorates Cancer-Related Indicators in Breast Cancer Patients and Survivors with Overweight/Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of combined aerobic and resistance training (CART) on body composition, lipid homeostasis, inflammation, adipokines, cancer-related fatigue, sleep, and quality of life in breast cancer patients and survivors with overweight/obesity. An electronic search was conducted in PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases from inception up to January 8, 2024. Randomized controlled trials (RCTs) meeting the inclusion criteria were selected for the analysis. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the quality of evidence. A random-effects model was used, and data were analyzed using mean (MD) and standardized mean differences (SMD) for continuous variables with 95% confidence intervals (CI). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. A total of 17 randomized controlled trials were included in the systematic review involving 1,148 female patients and survivors (mean age: 54.0 ± 3.4 years). The primary outcomes showed significant improvements in body mass index (SMD -0.57 kg/m, = 0.04), body fat (SMD -0.50%, = 0.02), fat mass (SMD -0.63 kg, = 0.04), hip circumference (MD -3.14 cm, = 0.02), and fat-free mass (SMD 1.03 kg, < 0.001). The secondary outcomes indicated significant increases in high-density lipoprotein cholesterol (MD -0.05 mmol/L, = 0.008), natural killer cells (SMD 0.42%, = 0.04), reductions in triglycerides (MD -81.90 mg/dL, < 0.01), total cholesterol (SMD -0.95 mmol/L, < 0.01), tumor necrosis factor α (SMD -0.89 pg/mL, = 0.03), and leptin (SMD -0.63 ng/mL, = 0.03). Also, beneficial alterations were found in cancer-related fatigue (SMD -0.98, = 0.03), sleep (SMD -1.17, < 0.001), and quality of life (SMD 2.94, = 0.02) scores. There was very low to low confidence in the estimated effect of most of the outcomes. The present findings reveal that CART could be considered an adjunct therapy in supporting the conventional clinical approach observed following exercise. However, further high-quality research is needed to evaluate whether CART would be a valuable intervention to lower aggressive pharmacologic use in breast cancer patients with overweight/obesity.
Topics: Humans; Breast Neoplasms; Female; Resistance Training; Cancer Survivors; Randomized Controlled Trials as Topic; Body Composition; Obesity; Quality of Life; Cardiometabolic Risk Factors; Adipokines; Exercise; Fatigue; Sleep; Overweight
PubMed: 38841642
DOI: 10.52082/jssm.2024.366 -
International Journal of Molecular... Apr 2024Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body... (Review)
Review
Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.
Topics: Humans; Animals; Obesity; Adipose Tissue; Adipokines; MicroRNAs; Gastrointestinal Microbiome; Adipose Tissue, Brown; Adipose Tissue, White; Inflammation Mediators; Energy Metabolism
PubMed: 38731880
DOI: 10.3390/ijms25094659 -
The Journal of Clinical Endocrinology... Dec 2023Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor...
CONTEXT
Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown.
OBJECTIVE
This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM.
METHODS
In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy.
RESULTS
Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway.
CONCLUSION
In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM.
Topics: Pregnancy; Animals; Mice; Humans; Female; Diabetes, Gestational; Adipokines; Insulin Resistance; Prediabetic State; Cohort Studies; Insulin
PubMed: 37440564
DOI: 10.1210/clinem/dgad413