Search Results (26)

Adiponectin (APN) is a secreted adipokine that plays a key role in modulating energy and bone metabolism, as well as regulating inflammatory responses. The overexpression of APN has been proposed as a potential therapeutic strategy for treating obesity and related disorders. Lipid nanoparticles (LNPs) are promising vectors for transporting messenger ribonucleic acid (mRNA) molecules. This study tested whether delivering a stabilized version of adiponectin mRNA (APN mRNA) using lipid nanoparticles could reduce fat formation and promote bone repair in vitro and in vivo. We demonstrated that transfection with APN-LNP upregulated the mRNA and protein expression of APN, while inhibiting adipogenesis in 3T3-L1 adipocytes. APN-LNP enhanced osteogenic gene expression in MC3T3-E1 cells in a dose-dependent manner. It also reduced matrix metalloproteinase 9 expression in receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated RAW264.7 cells, suggesting an anti-resorptive effect. In vivo, a femoral fracture model was established to explore the application of APN-LNP in promoting bone healing in diet-induced obese mice. Micro-computed tomography and histology analysis indicated that intravenous injection with APN-LNP promoted bone healing. Fasting blood glucose and body weight were decreased in the APN-LNP group. Moreover, APN-LNP increased bone sialoprotein and runt-related transcription factor 2 expression in contralateral femurs, as well as interleukin-10 expression in white adipose tissues. Thus, our study provides promising preclinical data on the potential use of APN-LNP for treating bone disorders in obesity. Full article

Adipose tissue of obese people secretes a number of adipokines, including adiponectin and resistin, which have an antagonistic effect on the human metabolism, influencing the pathogenesis of many diseases based on low-grade inflammation. Body composition analysis using bioelectrical impedance analysis (BIA) was performed in 84 adults with obesity, i.e., body mass index (BMI) greater than or equal to 30 kg/m². Serum was collected to analyze the concentration of adiponectin (ApN) and resistin. The subjects additionally completed a food frequency questionnaire FFQ-6 and a three-day food diary. Adiponectin-resistin index (AR index) was calculated. The results show a positive correlation between resistin levels and BMI and subcutaneous fat content. AR index value was also positively associated with the amount of adipose tissue and body mass. Adiponectin level in the serum of the studied individuals decreased with the content of lean tissue. Adiponectin level also decreased with the amount of carbohydrates, amount of starch, and glycemic load of the diet. Resistin decreased in patients who frequently consumed white pasta and red meat, while AR index was positively associated with the amount of white rice and saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) consumed but negatively associated with the frequent consumption of carbohydrates, including starch. Physical activity was negatively correlated with adiponectin levels and AR index. We concluded that body composition significantly influenced serum resistin and adiponectin concentrations the AR index. Dietary components also had a significant effect. Full article

Adiponectin (ApN) is a hormone with potent effects on various tissues. We previously demonstrated its ability to counteract Duchenne muscular dystrophy (DMD), a severe muscle disorder. However, its therapeutic use is limited. AdipoRon, an orally active ApN mimic, offers a promising alternative. While cardiomyopathy is the primary cause of mortality in DMD, the effects of ApN or AdipoRon on dystrophic hearts have not been investigated. Our recent findings demonstrated the significant protective effects of AdipoRon on dystrophic skeletal muscle. In this study, we investigated whether AdipoRon effects could be extended to dystrophic hearts. As cardiomyopathy develops late in mdx mice (DMD mouse model), 14-month-old mdx mice were orally treated for two months with AdipoRon at a dose of 50 mg/kg/day and then compared with untreated mdx and wild-type (WT) controls. Echocardiography revealed cardiac dysfunction and ventricular hypertrophy in mdx mice, which were fully reversed in AdipoRon-treated mice. AdipoRon also reduced markers of cardiac inflammation, oxidative stress, hypertrophy, and fibrosis while enhancing mitochondrial biogenesis via ApN receptor-1 and CAMKK2/AMPK pathways. Remarkably, treated mice also showed improved skeletal muscle strength and endurance. By offering protection to both cardiac and skeletal muscles, AdipoRon holds potential as a comprehensive therapeutic strategy for better managing DMD. Full article

Background/Objectives: Most cases of colorectal cancer (CRC) arise from adenomatous polyps. Identifying risk factors for colorectal adenoma (CRA) is critical for CRC prevention. Emerging evidence suggests a link between metabolic syndrome (MetS) and an elevated risk of CRA and CRC, potentially mediated by visceral obesity and adiponectin (APN). We aimed to evaluate the association between different markers of visceral obesity, serum APN, MetS, and the presence of CRA. Methods: A cross-sectional study was conducted at the University Clinical Center of Vojvodina, involving 120 patients, aged 40–75 years, who underwent colonoscopy between January 2022 and January 2023. Sixty patients with CRA were compared to 60 controls with normal colonoscopy findings. Visceral fat thickness (VFT) was measured using ultrasound (US), and bioelectrical impedance analysis (BIA) was used to assess visceral fat area (VFA). Serum APN levels, anthropometric measures, and MetS components were also evaluated. Results: Patients with CRA had significantly higher VFT measured by US (p < 0.05), but no significant differences were found in VFA measured by BIA, waist circumference (WC), or waist-to-hip ratio (WHR). MetS was significantly more prevalent in the CRA group (55% vs. 31.6%, p < 0.05), and logistic regression confirmed MetS as a significant predictor of CRA presence (OR = 2.6). Serum APN levels were inversely correlated with visceral fat measurements and MetS (p < 0.01), but no significant difference in APN levels was observed between patients with and without CRA. Conclusions: This study highlights the importance of VFT measured by US and the presence of MetS as significant factors associated with CRA. Full article

Glycolipid metabolic disorders (GLMD) refer to a series of metabolic disorders caused by abnormal processes of glucose and lipid synthesis, decomposition, and absorption in the body, leading to glucose and lipid excess, insulin resistance, and obesity. Probiotic intervention is a new strategy to alleviate metabolic syndrome. Lactobacillus paracasei JY062 (L. paracasei JY062) was separated from the Tibet-fermented dairy products. The results demonstrated a strong ability to relieve blood glucose disorders, blood lipid disorders, and tissue damage. The LPH group had the best effect, significantly decreasing the total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), leptin, insulin, and free fatty acid (FFA) concentrations and increasing the high-density lipoprotein cholesterol, adiponectin, and GLP-1 level compared to HFD-group mice. L. paracasei JY062 could activate the APN-AMPK pathway, increased AdipoQ, AMPK GLUT-4, and PGC-1α mRNA expression and decreased SREBP-1c, ACC, and FAS mRNA expression. L. paracasei JY062 intervention decreased the relative abundance of harmful bacteria, increased the relative abundance of beneficial bacteria, and restored the imbalance of gut microbiota homeostasis caused by a high-glucose-fat diet. L. paracasei JY062 alleviated glucolipid metabolism disorders via the adipoinsular axis and gut microbiota. This study provided a theoretical basis for probiotics to ameliorate glucolipid metabolism disorders by regulating the adipoinsular axis. Full article

Growing evidence suggests the involvement of adipose tissue in modulating the clinical course of relapsing–remitting multiple sclerosis (RRMS). This study aimed to investigate whether the intake of combined oral contraceptives (COCs) affects body weight and leptin and adiponectin (APN) blood levels in these patients. Clinical data from 62 women (M = 33.23 year) were recorded prior to the initiation of disease-modifying therapy. Patients who were taking COCs at the time of experiencing the first symptoms of disease (COC user) were compared with those who never used these formulations or stopped taking them before disease onset (COC non-user). Bivariate Pearson’s correlations and hierarchical multiple linear regressions analysis were conducted. Normalized APN levels were lower in the COC-using patients (p = 0.013). Negative correlations between waist circumference and normalized APN (p = 0.001) were observed only in the COC non-user patients. A longer duration of COC intake was associated with increased body mass index and waist circumference (p = 0.003). Normalized APN predicted the MS Severity Score (MSSS) (p = 0.020), but this correlation was lost in the COC user patients. After adjusting for confounders, only age (p = 0.027) and, later, disease onset (p = 0.014) were correlated with the MSSS. Larger and prospective studies are needed to investigate the interactions of sex steroids with adipose metabolism in modulating disease progression. Full article

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN’s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue’s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging. Full article

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. Full article

Age-related macular degeneration (AMD), a leading cause of irreversible blindness in adults, may result in poor central vision, making it difficult to see, read, and drive. AMD is generally classified in either dry or wet types. Milder cases of dry AMD may progress to geographic atrophy (GA), leading to significant visual disability; wet, or neovascular AMD, which involves choroidal neovascularization (CNV), can lead to complete loss of central vision. Adiponectin (APN) discovery in the mid-1990’s and, subsequently, its two cognate receptors (AdipoRs) in the early 2000s have led to a remarkable progress in better understanding metabolic disorders, as well as metabolism-associated ocular pathology. APN/AdipoRs signaling plays a central role in a variety of molecular and cellular physiological events, including glucose and lipid metabolism, whole-body energy regulation, immune and inflammation responses, insulin sensitivity and retinal cell biological functions. This review is an amalgamation of recent information related to APN/AdipoRs in the pathophysiology of retinal diseases and furthers its association with AMD and diabetic retinopathy. Additionally, we present our original research, where we designed control peptide and CNV inhibitory peptide from the globular region of APN to see the effect of these peptides on the mouse model of laser-induced CNV. The inhibitory peptide (APN1) inhibited CNV by more than 75% while the control peptide did not inhibit CNV. Full article

Adiponectin (APN) is an essential adipokine for a variety of reproductive processes. To investigate the role of APN in goat corpora lutea (CLs), CLs and sera from different luteal phases were collected for analysis. The results showed that the APN structure and content had no significant divergence in different luteal phases both in CLs and sera; however, high molecular weight APN was dominant in serum, while low molecular weight APN was more present in CLs. The luteal expression of both AdipoR1/2 and T-cadherin (T-Ca) increased on D11 and 17. APN and its receptors (AdipoR1/2 and T-Ca) were mainly expressed in goat luteal steroidogenic cells. The steroidogenesis and APN structure in pregnant CLs had a similar model as in the mid-cycle CLs. To further explore the effects and mechanisms of APN in CLs, steroidogenic cells from pregnant CLs were isolated to detect the AMPK-mediated pathway by the activation of APN (AdipoRon) and knockdown of APN receptors. The results revealed that P-AMPK in goat luteal cells increased after incubation with APN (1 μg/mL) or AdipoRon (25 μM) for 1 h, and progesterone (P4) and steroidogenic proteins levels (STAR/CYP11A1/HSD3B) decreased after 24 h. APN did not affect the steroidogenic protein expression when cells were pretreated with Compound C or SiAMPK. APN increased P-AMPK and reduced the CYP11A1 expression and P4 levels when cells were pretreated with SiAdipoR1 or SiT-Ca, while APN failed to affect P-AMPK, the CYP11A1 expression or the P4 levels when pretreated with SiAdipoR2. Therefore, the different structural forms of APN in CLs and sera may possess distinct functions; APN might regulate luteal steroidogenesis through AdipoR2 which is most likely dependent on AMPK. Full article

Lifestyle changes have led to increased incidence of cardiovascular disease (CVD); therefore, potential targets against CVD should be explored to mitigate its risks. Adiponectin (APN), an adipokine secreted by adipose tissue, has numerous beneficial effects against CVD related to glucose and lipid metabolism disorders, including regulation of glucose and lipid metabolism, increasing insulin sensitivity, reduction of oxidative stress and inflammation, protection of myocardial cells, and improvement in endothelial cell function. These effects demonstrate the anti-atherosclerotic and antihypertensive properties of APN, which could aid in improving myocardial hypertrophy, and reducing myocardial ischemia/reperfusion (MI/R) injury and myocardial infarction. APN can also be used for diagnosing and predicting heart failure. This review summarizes and discusses the role of APN in the treatment of CVD related to glucose and lipid metabolism disorders, and explores future APN research directions and clinical application prospects. Future studies should elucidate the signaling pathway network of APN cardiovascular protective effects, which will facilitate clinical trials targeting APN for CVD treatment in a clinical setting. Full article

An unhealthy diet can lead to the development of metabolic disorders. C-reactive protein (CRP) has been reported to be an inflammatory component of metabolic disorders. Additionally, reduced adiponectin (APN) levels is known as a predictor of metabolic disorders. We report on the beneficial effects of NBF1, an algal fiber-rich formula, on CRP, APN, and diabetes markers. Additionally, associations between dietary nutrients, CRP, and APN were investigated. A dietary survey that used a brief self-administered diet history questionnaire, a validated 58-item fixed-portion-type questionnaire, and a 4-week placebo-controlled dietary intervention were carried out. The latter consisted of a twice daily intake of 3 g of sujiaonori alga-based powder as a supplement (NBF1, n = 16), whereas the placebo group received the same amount of corn starch powder (n = 15). CRP and APN levels were assayed by ELISA. Clinical cases comprising three subjects with metabolic disorders treated with NBF1, including two type 2 diabetes mellitus patients and one subject with hypercholesterolemia, are also reported. They received 2.1g NBF1 once daily for 12 weeks. Intakes of algal fiber and n-3 PUFA were positively associated with the increase of APN, and n-3PUFA intake was inversely associated with CRP. All cases had improved metabolic health profile. Full article

Male-obesity-associated secondary hypogonadism (MOSH) is a very prevalent entity that may resolve after marked weight loss. Adiponectin (APN) is an adipokine with anti-inflammatory properties that regulates metabolism. Low-circulating APN is associated with obesity, diabetes, and cardiovascular risk, along with circulating testosterone. We aimed to evaluate APN changes in men with MOSH (low circulating free testosterone (FT) with low or normal gonadotropins) and without it after metabolic surgery. We look for their possible association with cardiovascular risk measured by carotid intima-media thickness (cIMT). We included 60 men (20 submitted to lifestyle modification, 20 to sleeve gastrectomy, and 20 to gastric bypass) evaluated at baseline and 6 months after. The increase in APN at follow-up was reduction in patients with persistent MOSH (n = 10) vs. those without MOSH (n = 30) and MOSH resolution (n = 20), and the former did not achieve a decrease in cIMT. The increase in APN correlated positively with FT (r = 0.320, p = 0.013) and inversely with cIMT (r = −0.283, p = 0.028). FT inversely correlated with cIMT (r = −0.269, p = 0.038). In conclusion, men without MOSH or with MOSH resolution showed a high increase in APN after weight loss with beneficial effects on cIMT. Those without MOSH resolution failed to attain these effects. Full article

There is a gap in understanding the effect of the essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary ω-3 (vs. ω-6 LCPUFA) supplementation promoted retinal vessel development. However, ω-6 (vs. ω-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including ω-3 and ω-6) in retinas under normoglycemic and hyperglycemic conditions. ω-3 (vs. ω-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both ω-3 and ω-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate ω-6 LCPUFA levels must be maintained in addition to ω-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the ω-3 and ω-6 LCPUFA’s protection against ROP. Full article

Body fat has been reported to be associated with a higher risk of fatty liver disease (FLD). However, few studies have explored the mediating roles of an inflammatory biomarker or adipokine on the relationships. Here, we examined the potential mediating roles of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and adiponectin (APN) in relationships between body fat and FLD in overweight and obese adults. Additionally, gender differences will be investigated. In total, 1221 participants aged 19–56 years were included in our study. Body fat percentage was measured with Dual Energy X-ray Absorptiometry (DEXA) and FLD by abdominal ultrasound. Mediation analysis was performed to assess the mediating effect of hsCRP, TNF-α and APN on the associations between BF (%) and FLD by gender differences. We found that hsCRP was significantly associated with body fat percentage in both genders (b = 0.2014, p < 0.0001 and b = 0.1804, p < 0.0001 for male and female, respectively), while hsCRP was associated with FLD only in the female group (b = 0.1609, p = 0.0109) but not in male group (b = 0.4800, p = 0.0603). We observed that hsCRP has a significant mediating effect on the association between body fat percentage and FLD (b = 0.0290, p = 0.0201, mediation ratio: 13.6%) in the female group independent of potential covariates (age, smoking, alcohol drinking and physical activity). TNF-α was not significantly associated with body fat percentage or FLD, with no mediating effect on the association between body fat percentage and FLD in either gender. In conclusion, there is a gender-specific mediation role of hsCRP in the association between body fat and FLD. HsCRP was a potential mediator on the association between adiposity and FLD in the female gender, but not in the male gender. Higher body fat was associated with a higher risk of FLD, and the inflammation level might play a potential mediating role in the association between body fat and FLD among female overweight and obese adults. Full article