Search Results (8)

Background/Objectives: Depression is a mood disorder that causes persistent sadness and loss of interest, and its etiology involves a condition known as hypoadiponectinemia, which is prevalent in depressive individuals compared with healthy individuals and causes neuroinflammation. The use of intact adiponectin protein to target neuroinflammation in depressive moods is complex due to the difficulties associated with using the intact protein. AdipoRon, a synthetic oral adiponectin receptor agonist that targets the AdipoR1 and AdipoR2 receptors for adiponectin, has emerged in this context. Its most prominent effects include reduced inflammation and the attenuation of oxidative stress. To the best of our knowledge, no comprehensive review has addressed these results so far. To fill this literature gap, we present a comprehensive review examining the effectiveness of AdipoRon in treating depression. Methods: Only preclinical models are included due to the absence of clinical studies. Results: Analyzing the included studies shows that AdipoRon demonstrates contrasting effects against depression. However, most of the evidence underscores AdipoRon-based adiponectin replacement therapies as potential candidates for future treatment against this critical psychiatric condition due to their anti-neuroinflammatory potential, ultimately inhibiting several neuroinflammatory pathways. Conclusions: Future research endeavors must address several limitations due to the heterogeneity of the studies’ methodologies and results. Full article

Alzheimer’s disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest for its potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, and mitigating tau hyperphosphorylation. This review aimed to evaluate the effects of AdipoRon-based adiponectin replacement therapy against AD, using a comprehensive approach grounded in the PICO framework—Population, Intervention, Comparison, and Outcomes. A total of six studies were reviewed, including in vitro and in vivo investigations examining AdipoRon’s impact on various AD models. These studies involved different cell lines and transgenic mouse models, assessing various outcomes such as cognitive function, neuroinflammation, tau phosphorylation, synaptic deficiencies, and relevant molecular pathways. By synthesizing data from these studies, our review thoroughly explains AdipoRon’s neuroprotective effects, mechanisms of action, and potential as a therapeutic agent for AD. This analysis aims to highlight the current state of knowledge, identify gaps in the research, and suggest directions for future studies and clinical applications. Full article

Chronic kidney disease (CKD) is linked to an elevated risk of malnutrition and sarcopenia, contributing to the intricate network of CKD-related metabolic disorders. Adipokines and myokines are markers and effectors of sarcopenia and nutritional status. The aim of this study was to assess whether the adipokine–myokine signature in patients on kidney replacement therapy could help identify malnutrition and sarcopenia. The study involved three groups: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, and 52 kidney transplant recipients (KTR). Mean age was 56.1 ± 16.3 years. Malnutrition was defined using the 7-Point Subjective Global Assessment (SGA) and the Malnutrition-Inflammation Score (MIS). Sarcopenia was diagnosed based on reduced handgrip strength (HGS) and diminished muscle mass. Concentrations of adipokines and myokines were determined using the enzyme-linked immunosorbent assay (ELISA). 32.8% of all study participants were identified as malnourished and 20.6% had sarcopenia. For malnutrition, assessed using the 7-Point SGA, in ROC analysis albumin (area under the curve (AUC) 0.67 was the best single biomarker identified. In dialysis patients, myostatin (AUC 0.79) and IL-6 (AUC 0.67) had a high discrimination value for sarcopenia, and we were able to develop a prediction model for sarcopenia, including age, albumin, adiponectin, and myostatin levels, with an AUC of 0.806 (95% CI: 0.721–0.891). Adipokines and myokines appear to be useful laboratory markers for assessing malnutrition and sarcopenia. The formula we propose could contribute to a better understanding of sarcopenia and potentially lead to more effective interventions and management strategies for dialysis patients. Full article

Ceruloplasmin is a ferroxidase that plays a role in iron homeostasis; its deficiency fosters inter alia iron accumulation in the liver, which expresses the soluble form of the protein secreted into the bloodstream. Ceruloplasmin is also secreted by the adipose tissue, but its role in adipocytes has been poorly investigated. We hypothesized that ceruloplasmin might have a role in iron/lipid interplay. We investigated iron/lipid dysmetabolism in the liver and adipose tissue of the ceruloplasmin-deficient mouse (CpKO) model of aceruloplasminemia and evaluated the effectiveness of ceruloplasmin replacement. We found that CpKO mice were overweight, showing adipose tissue accumulation, liver iron deposition and steatosis. In the adipose tissue of CpKO mice, iron homeostasis was not altered. Conversely, the levels of adiponectin and leptin adipokines behaved opposite to the wild-type. Increased macrophage infiltration was observed in adipose tissue and liver of CpKO mice, indicating tissue inflammation. The treatment of CpKO mice with ceruloplasmin limited liver iron accumulation and steatosis without normalizing the expression of iron homeostasis-related proteins. In the CpKO mice, the protein replacement limited macrophage infiltration in both adipose and hepatic tissues reduced the level of serum triglycerides, and partially recovered adipokines levels in the adipose tissue. These results underline the link between iron and lipid dysmetabolism in ceruloplasmin-deficient mice, suggesting that ceruloplasmin in adipose tissue has an anti-inflammatory role rather than a role in iron homeostasis. Furthermore, these data also indicate that ceruloplasmin replacement therapy may be effective at a systemic level. Full article

It has been reported that 17β-estradiol (E2) can exert beneficial effects against the development of obesity, providing women with a healthier metabolic profile and conferring cardiovascular protection. However, a growing body of evidence questions this role in the context of obesity and diabetes. We focus on the adipose tissue–heart axis to address the question of whether E2 can have metabolically detrimental effects in an obese-diabetic rat model. Female Zucker Diabetic Fatty rats were used: LEAN, fa/+; SHAM, sham-operated fa/fa; OVA, ovariectomized fa/fa, and OVA+E2, ovariectomized and E2 treated fa/fa. The secretory expression profile, tissue expansion parameters and composition of visceral adipose tissue, as well as systemic and cardiac parameters related to insulin resistance, fibrosis, and inflammation were analyzed. Ovariectomy induced an attenuation of both diabetic condition and metabolic dysfunction of adipose tissue and cardiac muscle in fa/fa rats, suggesting that E2, in the context of diabetes and obesity, loses its cardioprotective role and could even contribute to greater metabolic alterations. Adipose tissue from OVA rats showed a healthier hyperplastic expansion pattern, which could help maintain tissue function, increase adiponectin expression, and decrease pro-inflammatory adipokines. These findings should be taken into account when considering hormone replacement therapy for obese-diabetic women. Full article

Soybeans and hops have been traditionally used as a natural estrogen replacement therapy and their major active ingredients, isoflavones and prenylflavanones, are known to have estrogenic/antiestrogenic effects depending on the target organ. However, their potential benefits are still subject to controversies. The present study investigated the dual effect of soy isoflavones plus hop prenylflavanones (Soy-Hop) on bone loss and metabolic dysfunction under estrogen deficient condition. Rats were sham-operated (n = 10) or ovariectomized (OVX; n = 40) and then fed a high-fat diet (HFD) to develop hyperlipidemia in OVX rats within the experimental period of 8 weeks. The OVX/HFD rats were assigned to four groups to receive different doses of Soy-Hop (0, 30, 100, and 300 mg/kg) by oral gavage for 8 weeks. High-dose Soy-Hop significantly suppressed OVX/HFD-induced increases in food intake, body weight gain, fat mass, and circulating levels of leptin, adiponectin, LDL-cholesterol, total cholesterol, triglycerides, glucose, and insulin. High-dose Soy-Hop also attenuated OVX/HFD-induced elevation of osteocalcin, alkaline phosphatase, and CTX in plasma and RANKL/OPG gene expression ratio in femur. These findings were confirmed visually by confocal analysis of GLUT4 translocation in soleus muscle cells and micro-computed tomography scanning of the distal femoral epiphysis, respectively. These results suggest that Soy-Hop may have potential to ameliorate estrogen deficiency-related alterations in both metabolism and bone quality, at least in part, by hormonal factors secreted by adipocytes. Full article

Degenerative aortic stenosis (DAS) is the most frequently diagnosed heart valve disease in Europe and North America. DAS is a chronic progressive disease which resembles development of atherosclerosis. Endothelial dysfunction, lipid infiltration, calcification and ossification are evidenced in both diseases. The same risk factors such as older age, male sex, smoking, and elevated levels of lipids are identified. The effect of smoking, visceral obesity, metabolic syndrome, hypercholesterolemia, low-density lipoprotein, high-density lipoprotein, lipoprotein(a), adiponectin and apolipoprotein(a) on development of DAS are being studied. The search for genetic ties between disorders of lipid metabolism and DAS has been started. DAS is characterized by a long symptom-free period which can last for several decades. Aortic valve replacement surgery is necessary when the symptoms occur. The lipid-lowering therapy effect on stopping or at least slowing down the progression of DAS was studied. However, the results of the conducted clinical trials are controversial. In addition, calcium homeostasis, bone metabolism and calcinosis-reducing medication are being studied. Although prospective randomized clinical trials have not demonstrated any positive effect of statins used for slowing progression of the disease, statins are still recommended for patients with dyslipidemia. Recent study has suggested that a specific modification of treatment, based on severity of disease, may have a beneficial effect in patients with aortic sclerosis and mild DAS. New clinical studies analyzing new treatment possibilities which could correct the natural course of the disease and reduce the need for aortic valve replacement by surgery or transcatheter treatment interventions are needed. Full article

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. Full article