Inflammatory markers and adipokines alter adipocyte-derived ASP production through direct and indirect immune interaction. Lu H,Gauvreau D,Tom F-Q,Lapointe M,Luo X P,Cianflone K Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association Obesity and related metabolic diseases are associated with chronic low-grade inflammation, characterized by increased pro-inflammatory proteins. Several studies have demonstrated increases in acylation stimulating protein (ASP) and its precursor protein C3 in obesity, diabetes and dyslipidemia. To evaluate the effects of acute inflammatory factors and adipokines on ASP production and potential mechanisms of action, 3T3-L1 adipocytes were treated for 24 h with adipokines, cytokines, macrophage-conditioned media and direct co-culture with J774 macrophages. ASP and C3 in the media were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride stores). Leptin, adiponectin, IL-10, LPS and TNF-α increased ASP production (151%, 153%, 190%, 318%, 134%, P<0.05, respectively,). C5a and RANTES (Regulated and normal T cell expressed and secreted) decreased ASP production ( - 34%, - 47%, P<0.05), which was also associated with a decrease in the precursor protein C3 ( - 39% to - 51%, P<0.01), while keratinocyte chemoattractant (KC; murine IL-8 ortholog) had no effect on ASP and C3 secretion. By contrast, apelin, omentin and visfatin also decreased ASP ( - 27%, - 49%, - 22%, P<0.05), but without changes in precursor protein C3 secretion. Macrophage-conditioned media alone had little effect on C3 or ASP, while co-culture of adipocytes with macrophages markedly increased ASP and C3 production (272%, 167%, P<0.05). These in vitro results suggest various metabolic hormones and inflammatory factors can affect ASP production through increased precursor C3 production and/or by changing the rate of C3 conversion to ASP. As an adipokine, ASP could constitute a new link between adipocytes and macrophages. 10.1055/s-0032-1333231

Diagnostic and prognostic significance of apelin-13, APJ for sepsis in the emergency department: A prospective study. Heliyon Objectives:This study aimed to assess the diagnostic, risk stratification, and prognostic capabilities of apelin-13 and APJ in comparison to procalcitonin (PCT) for septic patients presenting to the emergency department (ED). Methods:Two hundred and thirty-eight patients meeting the Third International Consensus Definition (Sepsis-3) criteria were enrolled from Beijing Chaoyang Hospital's ED, along with a control group of forty healthy individuals. Patients were categorized into two groups based on disease severity: those with sepsis or septic shock. Plasma levels of apelin-13, CD4 Th cells, and PCT were measured. The expression levels of plasma APJ mRNA were quantified using real-time fluorescence quantitative PCR (RT-qPCR) methodology. The Sequential Organ Failure Assessment (SOFA) score was determined at the time of enrollment. The prognostic values of apelin-13 and APJ was evaluated in comparison to that of PCT and the SOFA score. All patients were followed up for a duration of 28 days. Results:The plasma concentrations of apelin-13 and APJ exhibited a positive correlation with the severity of sepsis, while the number of CD4 T cells decreased in septic patients. The areas under the receiver operating characteristic (AUC) curves for apelin-13 and APJ in the diagnosis and prediction of 28-day mortality were greater than that of PCT. In non-survivors at the 28-day follow-up, the plasma levels of apelin-13 and APJ were significantly higher compared to survivors. Furthermore, apelin-13 levels were notably higher in cases of sepsis-induced cardiomyopathy (SICM) than in those without SICM. Apelin-13 and APJ emerged as independent predictors of 28-day mortality among septic patients. Conclusions:Apelin-13 and APJ demonstrate value in the assessment of risk stratification, early diagnosis, and prognosis of sepsis in the ED. Apelin-13 also proves to be an effective biomarker for assessing the prognosis of SICM in the ED. Sepsis may lead to immune function suppression. 10.1016/j.heliyon.2024.e28620

Apelin-13 reduces lipopolysaccharide-induced neuroinflammation and cognitive impairment via promoting glucocorticoid receptor expression and nuclear translocation. Neuroscience letters Neuroinflammation is usually associated with cognitive decline, which is involved in neurodegenerative diseases. Apelin, a neuropeptide, exerts various biological roles in central nervous system. Recent evidence showed that apelin-13, an active form of apelin, suppresses neuroinflammation and improves cognitive decline in diverse pathological processes. However, the underlying mechanism of apelin-13 in neuroinflammation remains largely unknown. The present study aimed to determine underlying mechanism of apelin-13 on neuroinflammation-related cognitive decline. The lipopolysaccharide (LPS) intracerebroventricular (i.c.v.) to is used to establish a rat model of neuroinflammation-related cognitive decline. The results showed that apelin-13 inhibits LPS-induced neuroinflammation and improves cognitive impairment. Apelin-13 upregulates the GR level and nuclear translocation in hippocampus of rats. Moreover, glucocorticoid receptor inhibitor RU486 prevents apelin-13-mediated neuroprotective actions on cognitive function. Taken together, apelin-13 could exert a protective effect in neuroinflammation-mediated cognitive impairment via the activation of GR expression and nuclear translocation. 10.1016/j.neulet.2022.136850

Apelin signalling: a promising pathway from cloning to pharmacology. Masri B,Knibiehler B,Audigier Y Cellular signalling The discovery of new signalling pathways is always followed by the development of pharmacological agents as drugs that can be used in the treatment of diseases resulting from a dysfunction of the signalling pathway in question. Apelin signalling plays a role in the central and peripheral regulation of the cardiovascular system, in water and food intake, and possibly in immune function. Up-regulation of ligand and receptor is also associated with pathophysiological states such as cardiac dysfunction and neovascularisation. Finally, the apelin receptor is a coreceptor for the entry of several HIV-1 and SIV strains. In view of these features, the apelin receptor constitutes a very interesting target for the design of new drugs for treating the prime causes of human mortality. 10.1016/j.cellsig.2004.09.018

Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization. Hu Liuying,Hayashi Yumiko,Kidoya Hiroyasu,Takakura Nobuyuki Scientific reports The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Consistent with this, treating WT mice with [Pyr]Apelin-13 inhibited tumor growth. In MC38 tumors, only endothelial cells (ECs) strongly express APJ, a cognate receptor for Apelin, indicating that EC-derived Apelin might regulate tumor formation in an autocrine manner. Comparing with WT mice, larger numbers of vessels with narrower diameters were observed in tumors of Apelin knockout mice and lack of Apelin enhanced tumor hypoxia. Investigating immune cells in the tumor revealed that [Pyr]Apelin-13 infusion induced the accumulation of CD8 and CD4 T cells in central areas. Moreover, RNA-sequencing analysis showed that Apelin induces chemokine CCL8 expression in ECs. Thus, enhancing anti-tumor immunity might be one of the mechanisms by which Apelin is involved in tumor growth. Our result indicated that increased CCL8 expression might induce CD8  T cells infiltration into tumor and tumor inhibition. 10.1038/s41598-021-93619-5