Identification of Variants of Uncertain Significance in the Genes Associated with Thoracic Aortic Disease in Russian Patients with Nonsyndromic Sporadic Subtypes of the Disorder.

Nonsyndromic sporadic thoracic aortic aneurysm (nssTAA) is characterized by diverse genetic variants that may vary in different populations. Our aim was to identify clinically relevant variants in genes implicated in hereditary aneurysms in Russian patients with nssTAA. Forty-one patients with nssTAA without dissection were analyzed. Using massive parallel sequencing, we searched for variants in exons of 53 known disease-causing genes. Patients were found to have no (likely) pathogenic variants in the genes of hereditary TAA. Six variants of uncertain significance (VUSs) were identified in four (9.8%) patients. Three VUSs [FBN1 c.7841C>T (p.Ala2614Val), COL3A1 c.2498A>T (p.Lys833Ile), and MYH11 c.4993C>T (p.Arg1665Cys)] are located in genes with "definitive" disease association (ClinGen). The remaining variants are in "potentially diagnostic" genes or genes with experimental evidence of disease association [NOTCH1 c.964G>A (p.Val322Met), COL4A5 c.953C>G (p.Pro318Arg), and PLOD3 c.833G>A (p.Gly278Asp)]. Russian patients with nssTAA without dissection examined in this study have ≥1 VUSs in six known genes of hereditary TAA (FBN1, COL3A1, MYH11, NOTCH1, COL4A5, or PLOD3). Experimental studies expanded genetic testing, and clinical examination of patients and first/second-degree relatives may shift VUSs to the pathogenic (benign) category or to a new class of rare "predisposing" low-penetrance variants causing the pathology if combined with other risk factors.

CTRP13-Mediated Effects on Endothelial Cell Function and Their Potential Role in Obesity.

BACKGROUND: Obesity, a major component of cardiometabolic syndrome, contributes to the imbalance between pro- and anti-atherosclerotic factors via dysregulation of adipocytokine secretion. Among these adipocytokines, the C1q/TNF-related proteins (CTRPs) play a role in the modulation of atherosclerosis development and progression. Here, we investigated the vascular effects of CTRP13. RESULTS: CTRP13 is not only expressed in adipose tissue but also in vessels/endothelial cells (ECs) of mice, rats, and humans. Obese individuals (mice, rats, and humans) showed higher vascular CTRP13 expression. Human Umbilical Vein Endothelial Cells (HUVECs), cultured in the presence of serum from obese mice, mimicked this obesity-associated effect on CTRP13 protein expression. Similarly, high glucose conditions and TNF-alpha, but not insulin, resulted in a strong increase in CTRP13 in these cells. Recombinant CTRP13 induced a reduction in EC proliferation via AMPK. In addition, CTRP13 reduced cell cycle progression and increased p53 phosphorylation and p21 protein expression, but reduced Rb phosphorylation, with the effects largely depending on alpha-2 AMPK as suggested by adenoviral overexpression of dominant-negative (DN) or wild-type (WT) alpha 1/alpha 2 AMPK. CONCLUSION: The present study demonstrates that CTRP13 expression is induced in ECs under diabetic conditions and that CTRP13 possesses significant vaso-modulatory properties which may have an impact on vascular disease progression in patients.

Impact of a 12-Week Dietary Intervention on Adipose Tissue Metabolic Markers in Overweight Women of Reproductive Age.

The prevalence of overweight and obesity in women of reproductive age leads to significant health risks, including adverse metabolic and reproductive outcomes. Effective dietary interventions are critical to improving health outcomes in this population. This study investigates the impact of a 12-week diet intervention on metabolic markers of adipose tissue in overweight women of reproductive age, determining whether calorie restriction or low-starch diets are more effective, while also accounting for salivary amylase activity. A total of 67 overweight women of reproductive age were enrolled in a randomized controlled trial (RCT). Participants were divided into high-salivary-amylase (HSA) and low-salivary-amylase (LSA) groups based on baseline salivary amylase activity measured using a spectrophotometric method. Each group was further subdivided into two dietary intervention groups: calorie restriction (CR) and low starch (LS), resulting in four subgroups (HSA-CR, HSA-LS, LSA-CR, LSA-LS), along with a control group (CTR) of normal-weight individuals (no intervention). Participants were assigned to a calorie-restricted diet or a low-starch diet for 12 weeks. Key metabolic markers of adipose tissue, including insulin sensitivity, adipokines, cytokines, and lipid profiles, were measured at baseline (T0), 30 min after consuming starch-containing muesli (T1), and 12 weeks after intervention (T2). Active GLP-1, glucagon, and C-peptide levels were assessed to clarify the hormonal mechanisms underlying the dietary effects. Salivary amylase activity was also measured to examine its role in modulating glucose and GLP-1 responses. Both diet interventions led to significant improvements in metabolic markers of adipose tissue, though different ones. Calorie restriction improved insulin sensitivity by effectively reducing visceral fat mass and enhancing insulin signaling pathways. In contrast, the low-starch diet was linked to a reduction in the coefficient of glucose variation influenced partly by changes in GLP-1 levels. Our findings highlight the importance of personalized diet strategies to optimize metabolic health in this demographic.

Complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

METFORMIN MODULATED ADIPOKINES BIOCHEMICAL MARKERS IN TYPE-2 DIABETES PATIENTS.

Type 2 diabetes mellitus is the most widespread type of diabetes, mainly affecting adults. Long-term complications are related to the progression of type 2 diabetes mellitus. Metformin is a key treatment option for type 2 diabetes. OBJECTIVES: To evaluate serum irisin, visfatin, and RBP4 levels and to determine the effects of metformin treatment on irisin, visfatin, and RBP4 levels in patients with type 2 diabetes mellitus (Type 2 DM). MATERIAL AND METHODS: A total of 70 patients with type 2 diabetes mellitus, aged between 48 and 82 years were enrolled in the current study. Serum collected and irisin, visfatin, and RBP4 levels were measured, in Type 2 DM patients and control, using the ELISA Kit. RESULTS: The findings observed that there were significantly increased levels of irisin, visfatin, and RBP4 in patients with T2DM when compared with control groups. After 3 months of metformin treatment, irisin levels significantly decreased irisin, visfatin, and RBP4 in patients with T2DM when compared before treatment. Receiver operator characteristic curve investigation shows the levels of visfatin, and irisin are the best biomarkers differentiating subjects with T2DM. CONCLUSION: In patients with type 2 diabetes, 3 months of treatment with metformin reduces levels of Irisin, Visfatin, and RBP4.The clinical significance of these findings remains to be investigated.

Adipokines and Myokines as Markers of Malnutrition and Sarcopenia in Patients Receiving Kidney Replacement Therapy: An Observational, Cross-Sectional Study.

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.

Changes in adipokine indicators depending on A1166C polymorphism of the angiotensin II type 1 receptor gene as a predictor of the arterial hypertension.

Objective. Genetic factors substantially contribute to the development and duration of arterial hypertension. The study of the A1166C polymorphism of the angiotensin II type 1 receptor gene (AGTR1) in arterial hypertension is an auspicious area for assessing the relationship between heredity, hypertension development, and adipokines, but it still remains debatable. The purpose of the current study was to investigate serum adipokines levels depending on the AGTR1 A1166C polymorphism. Methods. A total of 86 patients with arterial hypertension were examined, who underwent the evaluation of the allelic A1166C polymorphism of AGTR1 by polymerase chain reaction with electrophoretic detection and determination of serum adipokines levels using enzyme-linked immunosorbent assay. Results. In the group of patients with arterial hypertension, a significant increase in serum adipokines (resistin, adiponectin, and leptin) levels was found against the background of a decrease in the antianorexic hormone ghrelin with a predominance of CC genotype carriers compared with AA genotype carriers of the AGTR1. A statistically significant decrease in ghrelin and an increase in serum adipokines (resistin, adiponectin, and leptin) in CC genotype carriers compared with AA genotype carriers of the AGTR1 were found suggesting that CC genotype carriers may be predictors of the development of arterial hypertension in our patients. Conclusions. Statistically significant decrease in ghrelin and increase in serum adipokines (resistin, adiponectin, and leptin) were found in CC genotype carriers compared with AA genotype carriers of the AGTR1, which suggests that carriers of the CC genotype are predictors of the arterial hypertension development in our patients.

Altered leptin level in autism spectrum disorder and meta-analysis of adipokines.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

Targeted next-generation sequencing reveals the genetic mechanism of Chinese Marfan syndrome cohort with ocular manifestation.

BACKGROUND: Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin-1 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan-like disorders. PURPOSE: To expand the mutation spectrum of FBN1 gene and validate the pathogenicity of Marfan-related genes in patients with MFS and ocular manifestations. METHODS: We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel-based next-generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases. RESULTS: We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan-related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G>A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families. CONCLUSION: We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan-related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity.

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

Obesity-induced chronic low-grade inflammation in adipose tissue: A pathway to Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, and insulin resistance (IR), which contribute substantially to the development of AD and subsequent morbidity and mortality. Adipose tissue (AT) is a highly dynamic organ composed of a diverse array of cell types, which can be classified based on their anatomic localization or cellular composition. The expansion and remodeling of AT in the context of obesity involves immunometabolic and functional shifts steered by the intertwined actions of multiple immune cells and cytokine signaling within AT, which contribute to the development of metabolic disorders, IR, and systemic markers of chronic low-grade inflammation. Chronic low-grade inflammation, a prolonged, low-dose stimulation by specific immunogens that can progress from localized sites and affect multiple organs throughout the body, leads to neurodystrophy, increased apoptosis, and disruption of homeostasis, manifesting as brain atrophy and AD-related pathology. In this review, we sought to elucidate the mechanisms by which AT contributes to the onset and progression of AD in obesity through the mediation of chronic low-grade inflammation, particularly focusing on the roles of adipokines and AT-resident immune cells.

[Correlation of posterior segment lesions with anterior segment biometric parameters and FBN1 genotype in patients with Marfan syndrome].

Objective: To investigate the characteristics of posterior segment lesions in Marfan syndrome (MFS) patients and their relationship with anterior segment biometric parameters and FBN1 genotype. Methods: A cross-sectional study was conducted. A total of 121 MFS patients, 76 males and 45 females, with an average age of (11.72±11.66) years, who visited the Department of Ophthalmology, Eye & ENT Hospital of Fudan University from January 2013 to March 2023 were included. The presence of posterior scleral staphyloma was observed using B-mode ultrasound, and macular lesions were identified and classified using the atrophy-traction-neovascularization system based on ultra-widefield fundus images, color fundus images, and optical coherence tomography scans. Anterior segment biometric parameters, including axial length of the eye, average corneal curvature, corneal astigmatism, horizontal corneal diameter, anterior chamber depth, and lens thickness, were collected, and the direction and extent of lens dislocation were observed. Molecular genetic analysis of FBN1 gene mutations in patients was performed using next-generation sequencing based on a panel of ocular genetic diseases, and the impact of the genotype and anterior segment biometric parameters on the posterior segment manifestations was analyzed. Results: Sixty patients exhibited posterior segment lesions, including retinal detachment (4 cases, 3.31%), macular lesions (47 cases, 38.84%), and posterior scleral staphyloma (54 cases, 44.63%). There was statistically significant difference in axial length of the eye between patients with and without posterior scleral staphyloma [23.09 (22.24, 24.43) and 27.04 (25.44, 28.88) mm], between patients with and without macular lesions [23.16 (22.24, 24.61) and 27.04 (25.74, 28.78) mm], and between patients with and without atrophic macular lesions [23.16 (22.24, 24.61) and 27.04 (25.74, 28.79) mm] (all P<0.001). There was statistically significant difference in anterior chamber depth between patients with and without macular lesions [3.11 (2.75, 3.30) and 3.34 (3.09, 3.60) mm] (P<0.05). There was also statistically significant difference in corneal astigmatism between patients with and without posterior scleral staphyloma [2.15 (1.20, 2.93) and 1.40 (1.00, 2.20) diopters] (P<0.05). The location and region of the FBN1 gene mutation not only showed statistically significant difference from the positive rates of posterior scleral staphyloma and macular lesions (all P<0.05), but also influenced the occurrence of atrophic macular lesions (both P<0.05). Patients with FBN1 mutations located in the transforming growth factor ß regulatory sequence had the highest proportion of posterior scleral staphyloma and macular lesions (both 10/11). Conclusions: Posterior scleral staphyloma and macular lesions have a relatively high incidence in MFS patients and tend to progress to more severe grades. The age, axial length of the eye, anterior chamber depth, corneal astigmatism, and location and region of the FBN1 gene mutation are factors affecting the posterior segment lesions in MFS patients.

Beneficial effects of a new probiotic formulation on adipocytokines, appetite-regulating hormones, and metabolic parameters in obese women.

Obesity is often accompanied by low-grade chronic inflammation and metabolic syndrome. It has been established that microbiota influences many physiological processes, including the development of obesity, and dysbiosis has been observed in obese individuals. In this study, we aimed to evaluate the impact of a new probiotic formulation, containing two probiotic strains and the bioactive compound octacosanol, on body weight, metabolic parameters, and concentrations of certain adipocytokines and appetite-regulating hormones in obese women. This double blind placebo-controlled supplementary intervention study included twenty-five women in the intervention group and twenty-three in the placebo group, and it lasted 12 weeks. Daily oral supplementation included 7 × 1010 CFU of Lactiplantibacillus plantarum 299v (DSM9843), 5 × 109 CFU of Saccharomyces cerevisiae var. boulardii (DBVPG6763), and 40 mg of octacosanol or placebo. Body weight, metabolic parameters, adipocytokines, and appetite-regulating hormones were assessed before (T0) and after the intervention (T1). After the intervention, significantly lower median concentrations of CRP (p = 0.005) and IL-6 (p = 0.012) were measured in the intervention group than the baseline, while the median concentrations of ghrelin (p = 0.026) and HDL-cholesterol (p = 0.03) were significantly increased. The intervention group had lower CRP levels (p = 0.023) and higher ghrelin levels (p = 0.006) than the placebo group. Significant changes in BMI between groups were not observed. In summary, although the new probiotic formulation showed beneficial effects on IL-6, CRP, HDL, and ghrelin levels, its potential effects on regulating triglyceride, insulin, and glucose levels require further studies before the novel dietary intervention could be considered a useful adjuvant therapy and an effective strategy for the management of obesity and obesity-associated comorbidities.

Adipokines-A Cohort Prospective Study in Children with Severe Burns.

Burns generate every year an important burden of morbidity, being a major global public health problem through prolonged hospitalization, complications, and increased mortality. This study's purpose was to evaluate the serum levels of three adipokines and to establish significant correlations with other circulating molecules and with some clinical parameters. We evaluated 32 children with severe burns (over 25% total burned surface area-TBSA) at 48 h, day 10, and day 21 post burn, and 21 controls. The serum levels of adiponectin, resistin, leptin, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) (among nine other biochemical parameters) were detected by Multiplex technique. Significant statistical differences were obtained for resistin and leptin compared to the control group, in different moments of measurements. Adiponectin serum levels presented statistically significant correlations with hot liquid mechanism of burn, the Revised Baux score, TBSA, resistin, PAI-1, CRP, TNF-α, and triglycerides (TGLs) serum levels. Resistin serum levels presented statistically significant correlations with adiponectin, CRP, PAI-1, leptin, and TNF-α. Additionally, we found statistically significant correlations between leptin serum levels and length of hospitalization, TNF-α, resistin, adiponectin, and PAI-1 serum levels. In severely burned children, adiponectin, resistin, and leptin specifically correlate with clinical parameters and with proteins involved in the systemic inflammatory response and the hypermetabolic response.

Leptin, Ghrelin, Irisin, Asprosin and Subfatin Changes in Obese Women: Effect of Exercise and Different Nutrition Types.

Background and Objectives: In this study, the effects of a six-week training program and various diets on subfatin, asprosin, irisin, leptin, ghrelin and the lipid profile were investigated in overweight women. Materials and Methods: A total of 78 women voluntarily participated in the study. Groups: The study was divided into eight groups: Healthy Control, Obese Control, Obese + Vegetarian, Obese + Ketogenic, Obese + Intermittent Fasting, Obese + Exercise + Vegetarian, Obese + Exercise + Ketogenic and Obese + Exercise + Intermittent Fasting. While there was no intervention in the healthy and obese control groups, the other groups followed predetermined exercise and diet programs for 6 weeks. Blood samples were taken from the participants in the research group twice (before and after the interventions). An autoanalyzer was used to determine the lipid profile in the blood samples taken, and the ELISA method was used to analyze other parameters. Results: Overall, a significant difference was found in the values of weight, BMI, subfatin, ghrelin, leptin, cholesterol, triglyceride, HDL and LDL as a result of the exercise and diet interventions (p < 0.05). There was no significant difference in asprosin and irisin values (p > 0.05). Conclusions: In conclusion, regular exercise and dietary interventions in obese women can regulate lipid profile, ghrelin, leptin and asprosin levels, and increasing irisin with exercise can activate lipid metabolism and support positive changes in lean mass.

The role of adipokines in the pathogenesis of psoriasis - a focus on resistin, omentin-1 and vaspin.

BACKGROUND: Psoriasis is a chronic immune-mediated skin condition with several types of manifestation, including psoriatic arthritis. In recent years, studies have demonstrated multiple molecules and mechanisms that play important roles in the pathophysiology of psoriasis. Studies have been conducted to determine the role of adipokines, bioactive peptides secreted by the adipose tissue, in the pathogenesis of inflammatory diseases. These studies have shown that adipokines are dysregulated in psoriasis and their abnormal expression profile could contribute to the inflammatory mechanisms observed in psoriasis. AREAS COVERED: In this review, we discuss the immunomodulatory features of resistin, omentin-1, and vaspin, and discuss their potential involvement in the pathogenesis of psoriasis. EXPERT OPINION: The adipokines resistin, omentin, and vaspin appear to be promising therapeutic targets in psoriasis. It is important to seek to block the action of resistin, either by blocking its receptors or by blocking its systemic effects with antibodies. In the case of omentin and vaspin, substances that are receptor mimetics of these adipokines should be sought and studies conducted of their analogues for the treatment of psoriasis. To introduce these therapies into clinical practice, multicentre clinical trials are required to confirm their efficacy and safety after initial studies in animal models.

Bone Marrow Adipose Tissue as a Critical Regulator of Postmenopausal Osteoporosis - A Concise Review.

Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.

Total Gestational Weight Gain Is Explained by Leptin and Body Fat, Regardless of Pre-Pregnancy Body Mass Index and Other Adipokines, in Mexican Adolescents.

Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.

Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals.

BACKGROUND: Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. METHODS AND RESULTS: One hundred eighty-one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age- and sex-matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P=4.6×10-6 [95% CI, 1.67-3.58]) and also somatic mosaic variants (OR, 4.71, P=0.026 [95% CI, 1.20-18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin-1). There was increased frequency of both missense and loss of function variants in TAA individuals. CONCLUSIONS: Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.

The role of asprosin in regulating ovarian granulosa- and theca-cell steroidogenesis: a review with comparisons to other adipokines.

Adipose tissues produce a variety of biologically active compounds, including cytokines, growth factors and adipokines. Adipokines are important as they function as endocrine hormones that are related to various metabolic and reproductive diseases. The goal of this review was to summarise the role of asprosin, a recently discovered adipokine, and compare its role in ovarian steroidogenesis with that of other adipokines including adiponectin, leptin, resistin, apelin, visfatin, chemerin, irisin, and gremlin 1. The summary of concentrations of these adipokines in humans, rats and other animals will help researchers identify appropriate doses to test in future studies. Review of the literature indicated that asprosin increases androstenedione production in theca cells (Tc), and when cotreated with FSH increases oestradiol production in granulosa cells (Gc). In comparison, other adipokines (1) stimulate Gc oestradiol production but inhibit Tc androgen production (adiponectin), (2) inhibit Gc oestradiol production and Tc androstenedione production (leptin and chemerin), (3) inhibit Gc steroidogenesis with no effect on Tc (resistin), (4) inhibit Gc oestradiol production but stimulate Tc androgen production (gremlin 1), and (5) increase steroid secretion by Gc, with unknown effects on Tc steroidogenesis (apelin and visfatin). Irisin has direct effects on Gc but its precise role (inhibitory or stimulatory) may be species dependent and its effects on Tc will require additional research. Thus, most adipokines have direct effects (either positive or negative) on steroid production in ovarian cells, but how they all work together to create a cumulative effect or disease will require further research.