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Elevated lipids in umbilical cord blood affect fetal programming, leading to a higher risk of developing cardiovascular disease in later life. However, the causes of changes in the lipid profile of umbilical cord blood are not clear yet. This study aimed for the first time to determine the association of asprosin concentration with TAG, TC, HDL-C, LDL-C concentrations and TAG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C/HDL-C ratio in umbilical cord blood as well as newborn anthropometric indices. This cross-sectional study was based on 450 mother- newborn pairs of a birth cohort study in Sabzevar, Iran. Multiple linear regression was used to estimate the association of lipid concentration and lipid ratios as well as birth weight (BW), birth length (BL), head circumference (HC) and chest circumference (CC) with asprosin in cord blood samples controlled for the relevant covariates. In fully adjusted models, each 1 ng/mL increase in asprosin was associated with 0.19 (95% CI 0.06, 0.31, P < 0.01), 0.19 (95% CI 0.10, 0.29, P < 0.01), 0.17 (95% CI 0.09, 0.25, P < 0.01), 0.17 (95% CI 0.09, 0.25, P < 0.01), 0.01 (95% CI 0.00, 0.013, P < 0.01), 0.01 (95% CI 0.01, 0.01, P < 0.01), 0.01 (95% CI 0.01, 0.01, P < 0.01) and 0.01 (95% CI 0.01, 0.01, P < 0.01) increase in TAG, TC, LDL-C, TAG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C/HDL-C ratio respectively. Moreover, higher asprosin levels was positively associated with newborn BW, BL, HC and CC; however, these associations were not statistically significant. Overall, our findings support the positive association between cord asprosin concentration and the development of atherogenic lipid profile in newborns. Further studies are needed to confirm the findings of this study in other populations.

Metabolic syndrome (MetS), is a non-communicable disorder caused by impaired management and storage of energy, primarily associated with unhealthy diets, sedentary lifestyles and stress. It is diagnosed when any three of the following conditions are observed, obesity (primary factor), hyperglycemia, low HDL, hypertriglyceridemia, and hypertension (ATP III guidelines). MetS affects approximately 14-34 % of the global population, highlighting significant public health concern. If left untreated, it leads to the development of other serious metabolic diseases like atherosclerosis, diabetes, PCOS, NAFLD, NASH, thyroid, cancer, sleep disturbance, osteoarthritis, anxiety, and depression. Despite ongoing research, no first-line drug currently exists for the comprehensive management of MetS. Its multifactorial nature often requires lifelong polytherapy with lifestyle intervention, raising concern over chronic drug use, drug-drug interactions, increasing morbidity and mortality. Therefore, there is a need highlighting the requirement of a single and targeted pharmacotherapy which offers a safer and more specific therapeutic approach. This review aims to identify and analyse ten key molecular targets in managing the pathogenesis of Metabolic Syndrome (MetS). These targets can further pave the way for a targeted and safer approach in the treatment of MetS. See also the graphical abstract(Fig. 1).

Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP–PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.

Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway.

Asprosin, a novel hormone released from white adipose tissue, regulates hepatic glucose metabolism and is pathologically elevated in the presence of insulin resistance. It is unknown whether aerobic exercise training affects asprosin levels in type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether (1) aerobic exercise training could decrease asprosin levels in the liver of streptozotocin (STZ)-induced diabetic rats and (2) the reduction in asprosin levels could induce asprosin-dependent downstream pathways. Five-week-old male Sprague–Dawley rats were randomly divided into control, STZ-induced diabetes (STZ), and STZ with aerobic exercise training groups (n = 6/group). T1DM was induced by a single dose of STZ (65 mg/kg intraperitoneally (i.p.)). The exercise group was made to run on a treadmill for 60 min at a speed of 20 m/min, 4 days per week for 8 weeks. Aerobic exercise training reduced the protein levels of asprosin, PKA, and TGF-β but increased those of AMPK, Akt, PGC-1β, and MnSOD. These results suggest that aerobic exercise training affects hepatic asprosin-dependent PKA/TGF-β and AMPK downstream pathways in T1DM.

Asprosin, a fasting-induced, glucogenic, and orexigenic adipokine, has gained popularity in recent years as a potential target in the fight against obesity and its complications. However, the contribution of asprosin to the development of moderate obesity-related inflammation remains still unknown. The present study aimed to evaluate the effect of asprosin on the inflammatory activation of adipocyte–macrophage co-cultures at various stages of differentiation. The study was performed on co-cultures of the murine 3T3L1 adipocyte and the RAW264.7 macrophage cell lines treated with asprosin before, during, and after 3T3L1 cell differentiation, with or without lipopolysaccharide (LPS) stimulation. Cell viability, overall cell activity, and the expression and release of key inflammatory cytokines were analyzed. In the concentration range of 50–100 nM, asprosin increased the pro-inflammatory activity in the mature co-culture and enhanced the expression and release of tumor necrosis factor α (TNF-α), high-mobility group box protein 1 (HMGB1), and interleukin 6 (IL-6). Macrophage migration was also increased, which could be related to the upregulated expression and release of monocyte chemoattractant protein-1 (MCP-1) by the adipocytes. In summary, asprosin exerted a pro-inflammatory effect on the mature adipocyte–macrophage co-culture and may contribute to the spread of moderate obesity-associated inflammation. Nevertheless, further research is needed to fully elucidate this process.

Objective: Asprosin, a novel peptide that has recently discovered as an important regulatory adipokine, is relevant to obesity in animals and adult humans. Little is known about its roles in children. The aim of the current study was to determine the potential role of asprosin and explore its relationship to various obesity-related markers in children with obesity. Methods: A cross-sectional study was conducted among 119 Chinese children, including 79 children with obesity and 40 lean controls. Anthropometric parameters, clinical data, and circulating tumor necrosis factor-α (TNF-α), adiponectin, leptin, and asprosin levels were measured. Results: Serum asprosin concentrations were significantly elevated in children with obesity compared with lean controls. Children with insulin resistance (IR) had higher asprosin levels than non-IR group. Asprosin was positively correlated with waist-to-hip ratio (WHR), diastolic blood pressure, homoeostasis model of IR (HOMA-IR), leptin-to-adiponectin ratio, TNF-α independent of their body mass index, SDs score, and age. In multivariable linear regression analysis, WHR and HOMA-IR were associated with the circulating level of asprosin. Conclusions: Circulating asprosins are increased in children with obesity and associated with IR. It may be proposed as a novel marker to predict advanced disease.

Background Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive. Methods Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE −/− mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [ 3 H]-labeled cholesterol. Results Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE −/− mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas. Conclusion Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE −/− mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.

To combine two indicators, asprosin and lipid accumulation product (LAP), to assess their predictive value for metabolic dysfunction-associated steatotic liver disease (MASLD) and to provide a more convenient and accurate option for mass screening of the MASLD population. Data were collected from 1249 adult subjects who underwent physical examination, LAP was calculated and serum asprosin was measured. Statistical analyses were performed and ROC curves were constructed to assess the predictive value of asprosin, LAP and their combination for MASLD. Asprosin and LAP levels were significantly higher in the MASLD group than in the non-MASLD group ( P < 0.001), and asprosin and LAP were independent risk factors for the development of MASLD ( P < 0.05).The combination of asprosin and LAP had the highest predictive efficacy for MASLD, and the AUCs were 0.841, 0.821 and 0.871 in the total, male and female populations, respectively. Asprosin and LAP are both good predictors of MASLD, and their combined performance is better than either indicator alone, and better in women than in men.The combination of asprosin and LAP may be an ideal marker for MASLD screening and individualised monitoring and management.

Aims/Introduction Asprosin is a novel secreted adipokine that is induced by fasting and promotes hepatic glucose release. In healthy humans, circulating asprosin shows circadian oscillation with an acute drop coinciding with the onset of eating. The present study investigated whether this circadian oscillation still exists in patients with type 2 diabetes mellitus. Materials and Methods We recruited 60 patients with type 2 diabetes mellitus and 60 individuals with normal glucose tolerance (NGT). All participants completed a 75‐g oral glucose tolerance test. Fasting and 2‐h postprandial serum asprosin concentrations were measured by the enzyme‐linked immunosorbent assay method. Partial correlation coefficients were calculated to analyze the relationships between serum asprosin level and parameters of glucose metabolism. Multiple logistic regression analysis was used to determine the association of serum asprosin level with diabetes. Results Both fasting and postprandial asprosin levels were significantly higher in patients with type 2 diabetes mellitus. The postprandial asprosin level was apparently lower than fasting asprosin level in individuals with NGT. The fasting asprosin level closely correlated with type 2 diabetes mellitus after multiple adjustment (odds ratio 2.329, P = 0.023). Asprosin correlated negatively with change in blood glucose (r = −0.502, P < 0.001) and change in C‐peptide (r = −0.467, P < 0.001) in individuals with NGT, but not in type 2 diabetes mellitus patients. Conclusions Serum asprosin level decreased coinciding with the onset of the oral glucose tolerance test in individuals with NGT, whereas this circadian oscillation was disturbed in type 2 diabetes mellitus patients. The impaired response of asprosin to glucose fluctuation in type 2 diabetes mellitus patients might be one of the reasons for the onset of type 2 diabetes mellitus. We found that serum asprosin level decreased coinciding with the onset of the oral glucose tolerance test in individuals with normal glucose tolerance, whereas this circadian oscillation was disturbed in type 2 diabetes patients. The response of asprosin to glucose fluctuation was impaired in type 2 diabetes patients, which might be one of the reasons for the onset of type 2 diabetes.