Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl is a widely distributed secreted protein in the body, involved in regulating glucose and lipid metabolism and maintaining cardiovascular system homeostasis. In this review, we present the predictive and therapeutic roles of Metrnl in various cardiovascular and metabolic diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, heart failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, and obesity.

UNASSIGNED: For the lack of effective serum markers for hepatocellular carcinoma(HCC) diagnosis, it is difficult to detect liver cancer and identify its recurrence early.
UNASSIGNED: Databases were used to analyze the genes potentially associated with alpha-fetoprotein(AFP). ELISA assay was used to detect the serum IL-41 in HCC, liver metastases, hepatitis, and healthy people. Immunohistochemical staining was used to analyze the relative quantification of IL-41 in HCC and paracancer tissues. Various survival curves were plotted according to clinical pathological data and helped us draw the ROC curve of IL-41 diagnosis of HCC.
UNASSIGNED: The serum expression of IL-41 was highest in AFP negative HCC patients and significantly higher than that in AFP positive HCC and metastatic cancer patients. There was a significant negative correlation between elevated serum IL-41 and AFP(<1500ng/ml). The clinicopathological features suggested that the serum IL-41 level was significantly correlated with capsule invasion, low differentiation and AFP. High serum expression of IL-41 suggests poorer survival and earlier recurrence after resection, and IL-41 upregulated in patients with early recurrence and death. The expression of IL-41 was higher in HCC tissues of patients with multiple tumors or microvascular invasion. The ROC curve showed that serum IL-41 had a sensitivity of 90.17 for HCC and a sensitivity of 96.63 for AFP-negative HCC, while the specificity was higher than 61%.
UNASSIGNED: IL-41 in serum and tissue suggests poor prognosis and postoperative recurrence in HCC patients and could be a new serum diagnostic marker for AFP negative patients.

UNASSIGNED: Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers.
UNASSIGNED: Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a post hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls.
UNASSIGNED: Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively).
UNASSIGNED: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment.
UNASSIGNED: https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.

UNASSIGNED: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression.
UNASSIGNED: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis.
UNASSIGNED: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis.
UNASSIGNED: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.

UNASSIGNED: Numerous studies have reported the beneficial effects of exercise and the use of herbal supplements in improving type 2 diabetes and insulin resistance. However, there are still many unanswered questions about the effects of cold and hot water, exercise, and herbal supplements on meteorine-like protein (METRNL), which is considered one of the key factors influencing insulin resistance improvement in this condition. Hence, the current study aimed to address these knowledge gaps and investigate the effects of 8 weeks of warm and cold-water swimming exercise with cinnamon consumption on serum levels of METRNL, histone deacetylase-5 (HDAC5), and insulin resistance in diabetic male rats.
UNASSIGNED: For this purpose, 70 diabetic male rats were randomly divided into seven groups (10 rats in each group) H ealthy control (HC) , Diabetic control , swimming training in cold water (temperature 5 °C) , swimming training at 5‌‌ °C + cinnamon consumption (200 mg/kg body weight) , swimming training in warm water (temperature 36-35 °C) , swimming training in warm water (temperature 36-35 °C) + consumption of cinnamon, and consumption of cinnamon only.
UNASSIGNED: The present study revealed a significant increase in serum METRNL concentration in the cold-water swimming + cinnamon consumption group (p < 0.05). However, no significant changes were observed in insulin levels and HOMA-IR across the different groups (p > 0.05). Additionally, noteworthy findings included a significant reduction in HDAC5 levels in both the cold-water swimming group and the cold-water swimming + cinnamon consumption group, as well as a significant decrease in fasting blood sugar (FBS) levels in all groups compared to the HC group (p < 0.05).
UNASSIGNED: The results of the present study demonstrate that the combination of cold-water swimming exercises and cinnamon extract consumption led to notable increases in serum METRNL concentration. Additionally, significant reductions were observed in HDAC5 and FBS levels. These findings highlight the potential effectiveness and benefits of the combination of cold-water swimming exercises and cinnamon extract consumption as an approach to improve diabetes-related indices.

BACKGROUND: Research on obesity, which results from excessive food consumption and sedentary lifestyle, has focused on increasing energy expenditure. Recently, muscle tissue is being investigated as an endocrine active organ, secreting molecules called myokines. Multiple studies have been performed to assess myokine levels in various disorders, including polycystic ovary syndrome (PCOS) and metabolic syndrome. Irisin and Meteorin-like protein (Metrnl) are particles which, among others, are suggested to play an important role in adipose tissue browning and improving insulin sensitivity.
METHODS: The study population consisted of 31 women with PCOS and 18 healthy individuals. PCOS was diagnosed based on revised 2003 Rotterdam criteria. Multiple anthropometrical, hormonal, and biochemical parameters were assessed, including oral glucose tolerance test and body composition with dual energy X-ray absorptiometry. Serum levels of irisin and Metrnl were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS: There were no differences between the PCOS and control groups according to age, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), or body mass composition. Assessment of Metrnl and irisin concentrations revealed no significant differences between PCOS and healthy women. The irisin level was negatively correlated with BMI, body fat mass, fasting glucose, and insulin concentrations. No relationship between Metrnl level and metabolic parameters was found.
CONCLUSIONS: Although irisin seems to be a promising biomarker, inconsistent research limits its value in clinical use in the assessment or treatment of obesity. Metrnl level was not affected in the study population, but it might be connected to the severity of metabolic disturbances.

Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl\'s clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.

Current study investigated the impact of maternal and postnatal overnutrition on phenotype of adipose, in relation to offspring thermogenesis and sex. Female C57BL/6 J mice were fed with CHOW or high fat diet (HFD) for 2 weeks before mating, throughout gestation and lactation. At weaning, pups were fed to 9 weeks old with CHOW or HFD, which resulted in four groups for each gender--male or female: CHOW-CHOW (CC), CHOW-HFD (CH), HFD-CHOW (HC), HFD-HFD (HH). Maternal and post-weaning HFD enhanced thermogenic factors such as Acox1, Dio2 and Cox8b in iBAT of male and female offspring, but increased SIRT1, PGC-1α and UCP1 only in female. However, Acox1, Dio2 and Cox8b mRNA expression and SIRT1, PGC-1α and UCP1 protein expression were only enhanced upon maternal and post-weaning HFD in sWAT and pWAT of female offspring. Increased metrnl expression in adipose were observed in sex- and depot-specific manner, while enhanced circulating metrnl level was only observed in male offspring undergoing maternal HFD. Palmitic acid changed metrnl expression during preadipocytes differentiation and siRNA-mediated knockdown of metrnl inhibited preadipocyte differentiation. Female offspring were more prone to resist adverse outcomes induced by maternal and post-weaning overnutrition, which probably related to metrnl expression and thermogenesis.

Hypertension, a prevalent cardiovascular ailment globally, can precipitate numerous complications, notably hypertensive cardiomyopathy. Meteorin-like (METRNL) is demonstrated to possess potential protective properties on cardiovascular diseases. However, its specific role and underlying mechanism in hypertensive myocardial hypertrophy remain elusive. Spontaneously hypertensive rats (SHRs) served as hypertensive models to explore the effects of METRNL on hypertension and its induced myocardial hypertrophy. The research results indicate that, in contrast to Wistar-Kyoto (WKY) rats, SHRs exhibit significant symptoms of hypertension and myocardial hypertrophy, but cardiac-specific overexpression (OE) of METRNL can partially ameliorate these symptoms. In H9c2 cardiomyocytes, METRNL suppresses Ang II-induced autophagy by controlling the BRCA2/Akt/mTOR signaling pathway. But when BRCA2 expression is knocked down, this effect will be suppressed. Collectively, METRNL emerges as a potential therapeutic target for hypertensive cardiomyopathy.

UNASSIGNED: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Metrnl is a secreted protein that plays an important role in kidney disease. The aim of this study was to investigate DKD-related factors and the correlation between serum Metrnl levels and the severity of DKD.
UNASSIGNED: Ninety-six type 2 diabetes mellitus (T2DM) patients and 45 DKD patients were included in the study. A range of parameters were measured simultaneously, including waist-to-hip ratio (WHR), body mass index (BMI), urinary albumin/creatinine ratio (UACR), monocyte-lymphocyte ratio (MLR), albumin/globulin (A/G), liver and kidney function, blood lipid profile, islet function, and others. Subsequently, the related factors and predictive significance of DKD were identified. The correlation between the relevant factors of DKD and serum Metrnl levels with DKD was evaluated.
UNASSIGNED: The duration of the disease (OR: 1.12, 95% CI: 1.01-1.24, P=0.031), hypertension (OR: 4.86, 95% CI: 1.16-20.49, P=0.031), fasting blood glucose (OR: 1.23, 95% CI: 1.03-1.48, P=0.025), WHR (OR: 2.53, 95% CI: 1.03-6.22, P=0.044), and MLR (OR: 1.91, 95% CI: 1.18-3.08, P=0.008) are independent risk factors for DKD (P < 0.05). Conversely, A/G (OR: 0.13, 95% CI: 0.02-0.76, P=0.024) and Metrnl (OR: 0.99, 95% CI: 0.98-1.00, P=0.001) have been identified as protective factors against DKD. Furthermore, the level of Metrnl was negatively correlated with the severity of DKD (rs=-0.447, P<0.001). The area under receiver operating characteristic (ROC) curves for the diagnostic accuracy of Metrnl for DKD is 0.765 (95% CI: 0.686-0.844).
UNASSIGNED: The duration of the disease, hypertension, fasting blood glucose, WHR, and MLR are major risk factors for DKD. Metrnl and A/G are protective factors for DKD. Serum Metrnl concentrations are inversely correlated with DKD severity.