Acylation-stimulating Protein Levels Research Articles

Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis.

It is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a variety of complement components, and the relationship between complement components and the risk and severity of NAFLD is inconsistent. The aim of this meta-analysis was to evaluate the association of complement components with the risk and severity of NAFLD. We searched PubMed, Embase, Cochrane Library, Google Scholar, Scopus, and ZhiWang Chinese databases from inception to May 2022 for observational studies reporting the risk of NAFLD with complement components. Random-effects meta-analysis was used to obtain pooled estimates of the effect due to heterogeneity. We identified 18 studies with a total of 18560 included subjects. According to recent studies, levels of complement component 3 (C3) (mean difference (MD): 0.43, 95% confidence interval (CI) 0.26-0.60), complement component 4 (C4) (MD: 0.04, 95% CI 0.02-0.07), complement component 5(C5) (MD: 34.03, 95% CI 30.80-37.27), complement factor B (CFB) (MD: 0.22, 95% CI 0.13-0.31) and acylation stimulating protein (ASP) (standard mean difference (SMD): 5.17, 95% CI 2.57-7.77) in patients with NAFLD were significantly higher than those in the control group. However, no statistical significance was obtained in complement factor D (CFD) levels between NAFLD and non-NAFLD (MD=156.51, 95% CI -59.38-372.40). Moreover, the levels of C3, C5, CFB, and ASP in patients with moderate and severe NAFLD were significantly higher than those in patients with mild NAFLD. Except for C4 and CFD, the included studies did not explore the changes in the severity of NAFLD according to the concentration of C4 and CFD. This meta-analysis demonstrates that an increase in complement components including C3, C5, CFB, and ASP is associated with an increased risk and severity of NAFLD, indicating that they may be good biomarkers and targets for the diagnosis and treatment of NAFLD. PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42022348650.

Acylation-stimulating protein and heart failure progression in arrhythmogenic right ventricular cardiomyopathy.

Our previous studies suggested that the complement system was critical in the prognosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). The acylation-stimulating protein (ASP), generated through the alternate complement pathway, was reported to regulate lipogenesis and triglyceride storage. This study aimed to investigate the role of ASP in predicting adverse cardiac events in an ARVC cohort. We enrolled 111 ARVC patients and 106 healthy volunteers, and measured their plasma ASP levels using enzyme-linked immunosorbent assays. Plasma ASP levels were significantly higher in the ARVC patients than in the healthy controls (2325.22±20.08 vs. 2189.75±15.55, P<0.001), with a similar trend observed in the myocardial explant assay. Spearman correlation analysis indicated plasma ASP level associated with cardiac structural (right ventricular internal dimension, P=0.006) and functional remodelling (left ventricular ejection fraction, P=0.002) in ARVC patients. The ARVC patients were followed up for an average of 17.79±1.09months. Heart failure-associated events (HFAEs) were defined as heart transplantation, on a cardiac transplant list, or death due to end-stage heart failure. Plasma ASP levels in patients with HFAEs were significantly higher than in those without clinical events (2486.03±26.70 vs. 2268.83±23.51, P<0.001) or those with malignant arrhythmic events (2486.03±26.70 vs. 2297.80±60.46, P=0.008). LASSO (least absolute shrinkage and selection operator) and multivariable Cox regression analyses showed the ASP level (HR=1.004, 95% CI [1.002,1.006], P=0.002) was an independent predictor for adverse HFAEs in ARVC patients. The spline-fitting procedure was applied to illustrate the HFAE-free probabilities at different time points. Our results suggest that plasma ASP may be a useful biomarker in prediction of adverse HF-associated events in ARVC patients.

Roux-en-Y Gastric Bypass Surgery Has Early Differential Effects on Bile Acids and the Levels of Complement Component 3 and Acylation-Stimulating Protein.

Bile acids have been implicated in the mechanism by which Roux-en-Y gastric bypass (RYGB) can induce remission of type 2 diabetes (T2D). Our goal was to identify circulating proteins whose levels changed after RYGB when dysglycemic parameters normalized. This was a retrospective study of 26 participants who underwent RYGB. Blood proteins were identified using two-dimensional electrophoresis and mass spectroscopy. Complement proteins were measured using immunoassays and bile acids measured using ultra-high-performance liquid chromatography and mass spectroscopy. A total of 7/452 blood proteins were found to change 2days after RYGB. Complement component 3 (C3) was selected because of its regulation by bile acids and the glucoregulatory function of its proteolytically processed product C3adesArg or acylation-stimulating protein (ASP). The median (inter-quartile range/IQR) C3 level was 47.4 (34.5, 65.9) mg/dL before surgery decreasing to 40.9 (13.4, 64.1) mg/dL within 2days after surgery (p = 0.0292). The median (IQR) ASP level increased from 2.8 (0.9, 7.3) nM before surgery to 8.0 (5.3, 14.1) nM within 2days after surgery (p = 0.0016). ASP levels increased in 14/17 (82%) with T2D remission and in 6/6 with normoglycemia but decreased in 3/3 with persistent T2D. Of ten bile acids measured, the levels of ursodeoxycholic acid (UDCA) were significantly decreased after RYGB and the levels of taurodeoxycholic acid (TDCA) were significantly decreased with T2D remission. These data further support an association of C3 with glucose metabolism and implicate bile acids and ASP in the early remittive effects of RYGB on T2D.

The Effect of Atorvastatin (and Subsequent Metformin) on Adipose Tissue Acylation-Stimulatory-Protein Concentration and Inflammatory Biomarkers in Overweight/Obese Women With Polycystic Ovary Syndrome.

Background: Atorvastatin has been shown to improve cardiovascular risk (CVR) indices in women with polycystic ovary syndrome (PCOS). Low-grade chronic inflammation of adipose tissue may link PCOS and adverse CVR. In pro-inflammatory states such as PCOS, spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index.Methods: The objective of this study was to determine the effect of atorvastatin on markers of adipose tissue dysfunction and inflammation; acylation-stimulating-protein (ASP), interleukin-6 (IL-6), and monocyte-chemoattractant-protein-1 (MCP-1) in PCOS. This was a randomized, double-blind, placebo-controlled study where 40 medication-naive women with PCOS and biochemical hyperandrogenaemia were randomized to either atorvastatin 20 mg daily or placebo for 12 weeks. Following the 12 week randomization; both group of women with PCOS were subsequently started on metformin 1,500 mg daily for further 12 weeks to assess whether pre-treatment with atorvastatin potentiates the effects of metformin on markers of adipose tissue function We conducted a post-hoc review to detect plasma ASP and the pro-inflammatory cytokines IL6 and MCP-1 before and after 12 and 24 weeks of treatment.Results: There was significant reduction in ASP (156.7 ± 16.2 vs. 124.4 ± 14.8 ng/ml p <0.01), IL-6 (1.48 ± 0.29 vs.0.73 ± 0.34 pg/ml p = 0.01) and MCP-1 (30.4 ± 4.2 vs. 23.0 ± 4.5 pg/ml p = 0.02) after 12 weeks of atorvastatin that was maintained subsequently with 12 weeks treatment with metformin. There was a significant positive correlation between ASP levels with CRP (p < 0.01), testosterone (p < 0.01) and HOMA-IR (p < 0.01); IL-6 levels with CRP (p <0.01) and testosterone (p < 0.01) and MCP-1 with CRP (p < 0.01); testosterone (p < 0.01) and HOMA-IR (p < 0.02).Conclusions: This post-hoc analysis revealed that 12 weeks of atorvastatin treatment significantly decreased the markers of adipose tissue dysfunction and inflammation, namely ASP, IL-6 and MCP-1 in obese women with PCOS. Changes in adipose tissue markers were significantly associative with substantial improvements in HOMA-IR, testosterone and hs-CRP levels.ISRCTN Number: ISRCTN24474824.

Association of A:O ratio with metabolic risk markers in North Indian women

BackgroundPlasma concentrations of Acylation stimulating protein (ASP) and Orexin-A are closely linked to body weight and energy homeostasis. The purpose of this study is to describe the associations of A:O with metabolic risk marker in women. MethodsThis is a case control study. Total 382 women were recruited for the study.192 women with metabolic syndrome (WmetS) &190 women without metabolic syndrome (WometS) according to NCEP-ATPIII guidelines. Serum ASP and Orexin-A level were determined by enzyme linked immunosorbent assay. ResultsResult indicated that Waist Circumference, Blood pressure, Lipid profile, Glucose (FPG), Insulin resistance (HOMA-IR), ASP and A:O ratio were significantly higher but HDL and Orexin-A level were significantly lower in WmetS than WometS. The correlation of ASP, A:O ratio were positively significant correlated with Waist Circumference (WC), Triglyceride (TG), Glucose (FPG) and negatively significant correlated with High density lipoprotein (HDL), however the orexin-A was negatively significant correlated with WC and TG in WmetS. ConclusionThe study concluded that A:O ratio may be one of the potential biomarker for metabolic syndrome.

Association of acylation stimulating protein and adiponectin with metabolic risk marker in North Indian obese women

BackgroundPlasma concentrations of Acylation stimulating protein (ASP) and adiponectin are associated with body weight and energy homeostasis. The purpose of this study is to describe the potential role of acylation stimulating protein and adiponectin with metabolic risk marker in North Indian obese women. MethodsThis is a case control study. Total 520 women were recruited for the study n = 260 women with obesity (BMI>30) study group and n = 260 women without obesity (BMI<25) control group. Serum ASP and adiponectin level were determined by enzyme linked immunosorbent assay. ResultsResult indicated that WC, BP, lipid profile, FPG, FPI, IR (HOMA-IR), ASP were significantly higher but adiponectin and HDL were significantly lower in women with obesity than in women without obesity. Furthermore ASP was significantly positive correlated with WC, FPG, TG, VLDL, FPI and IR, whereas the correlation of adiponectin was significantly negative correlated with WC, FPG, TG, IR, ASP and significantly positive correlated with HDL in women with obesity. ConclusionThe study shows that high level of ASP and low level of Adiponectin could be a potential marker of women with obesity among metabolic syndrome.

Acylation-stimulating protein is a surrogate biomarker for acute myocardial infarction: Role of statins.

BACKGROUND:Acylation-stimulating protein (ASP) is an adipokine synthesized within adipocytes environment due to adipocyte differentiation.AIM:The aim of this study was to assess changes in ASP levels in patients with acute myocardial infarction (MI) and to correlate these variations with disease variables.SUBJECTS AND METHODS:A total number of 111 patients previously and currently treated with rosuvastatin or atorvastatin presented with acute MI in a Coronary Care Unit, were divided into three groups, Group A: Thirty-nine patients treated with atorvastatin, Group B: Thirty patients treated with rosuvastatin, compared to 42 patients presented with MI not previously treated with statins were enrolled in this study. ASP and troponin-I levels and lipid profile were estimated in each group.RESULTS:The effects of atorvastatin and rosuvastatin compared to nonstatins-treated group on the anthropometric and biochemical variables in patients with acute MI showed significant difference in all biochemical and anthropometric parameters P < 0.05. Serum ASP (nmol/l) levels were higher in control patients 57.25 ± 9.15 compared to atorvastatin-treated patients 48.43 ± 7.42 and rosuvastatin-treated patients 49.33 ± 6.52 P = 0.0124.CONCLUSION:ASP levels are elevated in patients with acute MI and regarded as surrogate biomarker for acute MI also; therapy with statins leads to significant reduction in ASP levels compared to nonstatins-treated patients that presented with acute MI.

An increase level of acylation stimulating protein is correlated with metabolic risk markers in North Indian obese women

Background and aimsThe present study was to investigate the association between serum acylation stimulating protein (ASP) level with metabolic risk factors in North Indian obese women. MethodsThis is a case control study, total n=322 women aged between 20 and 45 years (n=162 with metabolic syndrome & n=160 without metabolic syndrome) were recruited for the study according to National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Serum ASP level were determined by enzyme linked immunosorbent assay. ResultsResults indicated that circulating ASP and other metabolic risk factors (waist circumference, triglycerides, fasting plasma glucose etc) were significantly higher in women with metabolic syndrome (WmetS) than in women without syndrome (WometS) (p<0.001). Furthermore circulating ASP was significantly higher possitively correlated with waist circumference (r=0.51, p<0.001), triglyceride (r=0.56, p<0.001), glucose (r=0.70, p<0.001), and negatively correlated with high density lipoprotein(r=−0.56, p<0.001) in women with metabolic syndrome. ConclusionsConclusively circulating ASP was found to be significantly associated with hyperlipidemia, obesity and obesity related disorders in North Indian obese women.

Components of the alternative complement pathway in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease. Adipose tissue plays important roles in the events that regulate body metabolism. This study determined the levels of complement 3 ( C3), acylation-stimulating protein (ASP), and adipsin, which take part in the alternate complement pathway, and are synthesized in and secreted by adipose tissue. Thirty-two patients with psoriasis were matched with 22 controls in terms of age, sex, body mass index, and lipid profiles. Serum C3, ASP, and adipsin levels were measured in both groups. The serum C3 level was higher and ASP and adipsin levels were lower in the patient group, but these differences were not significant (p = 0.708, p = 0.628, and p = 0.218, respectively). ASP and adipsin levels were correlated positively in patients with psoriasis (p = 0.029). To our knowledge, this study is the first to evaluate ASP and adipsin levels in patients with psoriasis. The roles of ASP and adipsin in the etiopathogenesis of psoriasis are unclear. Although not statistically significant, the lower ASP and adipsin levels in the patient group suggest a potential anti-inflammatory role of these proteins in psoriasis. Further studies should examine the relationships between ASP/adipsin and psoriasis.

Low acylation stimulating protein levels are associated with cardiometabolic disorders-secondary to autoimmune activation?

Objective:We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation.Methods:Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as “healthy.”Results:ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in “healthy” men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values ≥22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF <22 nmol/L. In linear regression analyses in the whole sample, ASP was inversely associated independently with PAF and PAF-AH and, in men, positively with Lp(a) and sex hormone-binding globulin. Prevalent and (at 2.0 years’ follow-up) incident metabolic syndrome (MetS, n=393), diabetes (n=154), and coronary heart disease (CHD, n=171) were analyzed by sex-, age-, and Lp(a)-adjusted logistic regression, using tertiles of ASP and PAF. The lower two (<42 nmol/L) ASP tertiles were a risk factor in combined sexes for MetS and diabetes. In women, incident CHD was predicted by either reduced or elevated ASP tertiles.Conclusion:Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for “reduced” values and increased likelihood of cardiometabolic disorders.

Persistent Complement Activation is Associated with Insulin Resistance and Chronic Inflammation in Overweight Patients with Type 2 Diabetes with Dyslipidemia

Insulin resistance is a major player in the pathogenesis of type 2 diabetes. C3 converts to C3a and acylation stimulating protein (ASP) by complement activation. ASP activates adipose tissue macrophages and accelerates continuous inflammation. Tissuebound C3a is known to induce insulin resistance. We examined the relationship between insulin resistance and complement activation by the in vivo alteration of ASP. The levels of ASP and parameters of insulin resistance and inflammation were measured in plasma from 25 patients with type 2 diabetes. A selective peroxisome proliferator-activated receptor gamma (PPAR) agonist was administered to these 25 patients for three months, and then ASP and the parameters were measured again. The alterations of ASP and the parameters were examined in the pathophysiological state. Plasma levels of ASP and complement activation products were significantly higher in diabetes. Parameters of insulin resistance were also significantly increased. The ASP level significantly improved after PPAR agonist administration. The improvement in ASP level correlated with improvements in parameters of insulin resistance and inflammation. The levels of other relevant adipocytokines by insulin resistance correlated with the degree of inflammation. ASP and complement activation were associated with insulin resistance and chronic inflammation in diabetes.

Relationships among acylation-stimulating protein, insulin resistance, lipometabolism, and fetal growth in gestational diabetes mellitus women

The aim of this study was to investigate the potential relationship between acylation-stimulating protein (ASP), insulin resistance, lipometabolism, the intrauterine metabolic environment and fetal growth in well-controlled gestational diabetes mellitus (GDM) women. A total of 55 well-controlled GDM women, 66 pregnant women with normal glucose tolerance (NGT) and their newborns, were included in this study. Fasting maternal and cord blood ASP, serum lipid profiles, glucose level, insulin level, HOMA-IR, in addition to neonatal anthropometry data, were measured. Maternal blood ASP in GDM is higher than that in NGT. In the GDM group, maternal blood ASP has a positive correlation with TG, FFA and HOMA-IR. Maternal and cord blood ASP levels of LGA fetuses correlate with elevated birth weight and SF4. Similarly, cord blood ASP levels of LGA fetuses also correlate with birth weight and SF4 in the NGT group. The maternal blood ASP level of GDM mothers is associated with lipometabolism, insulin resistance and LGA fetal growth. Nevertheless, the cord blood ASP level correlates with FFA of GDM mothers, LGA fetal growth of GDM and NGT mothers. ASP may be a biomarker for evaluating insulin resistance of GDM and LGA fetal growth.

Levels of acylation stimulating protein and the complement component 3 precursor are associated with the occurrence and development of coronary heart disease.

The aim of the present study was to investigate whether acylation stimulating protein (ASP) and complement component 3 (C3) are associated with the occurrence and development of coronary heart disease (CHD). The participants of the study were divided into three groups, including the healthy control (n=42), metabolic syndrome (MS, n=56) and CHD (n=62) groups. An enzyme-linked immunosorbent assay was used to measure the ASP concentrations, while an immunoturbidimetric assay was employed to determine the C3 concentrations. In addition, coronary angiography was performed to determine the severity of coronary artery disease in the CHD group. The CHD group was divided into three subgroups, according to the final Gensini score of coronary artery stenosis for each patient (mild, ≤20 points; moderate, 21–40 points; severe, >40 points). Western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed to analyze the protein and mRNA expression levels of C3 in the CHD subgroups and the healthy control group. The concentrations of ASP and C3 in the CHD group were found to be significantly higher compared with the control and MS groups. In addition, the levels of ASP and C3 in the mild and moderate CHD subgroups were significantly higher compared with the healthy controls or mild CHD patients. Furthermore, the protein expression levels of C3 in the moderate and severe CHD patients were found to be significantly higher compared with the healthy individuals and the mild CHD patients. The quantitative RT-PCR results revealed that the mRNA expression levels of C3 in the moderate and severe CHD patients were significantly higher compared with the healthy control group and the mild CHD patients. Furthermore, the mean levels of C3 transcripts in the severe CHD patients were found to be higher compared with the moderate CHD subgroup (P<0.05). Therefore, ASP and C3 were found to be associated with the occurrence and development of CHD; thus, may be used as novel indexes for CHD.

Acylation stimulating protein, complement C3 and lipid metabolism in ketosis-prone diabetic subjects.

BackgroundKetosis-prone diabetes (KPDM) is new-onset diabetic ketoacidosis without precipitating factors in non-type 1 diabetic patients; after management, some are withdrawn from exogenous insulin, although determining factors remain unclear.MethodsTwenty KPDM patients and twelve type 1 diabetic patients (T1DM), evaluated at baseline, 12 and 24 months with/without insulin maintenance underwent a standardized mixed-meal tolerance test (MMTT) for 2 h.ResultsAt baseline, triglyceride and C3 were higher during MMTT in KPDM vs. T1DM (p<0.0001) with no differences in non-esterified fatty acids (NEFA) while Acylation Stimulating Protein (ASP) tended to be higher. Within 12 months, 11 KPDM were withdrawn from insulin treatment (KPDM-ins), while 9 were maintained (KPDM+ins). NEFA was lower in KPDM-ins vs. KPDM+ins at baseline (p = 0.0006), 12 months (p<0.0001) and 24 months (p<0.0001) during MMTT. NEFA in KPDM-ins decreased over 30–120 minutes (p<0.05), but not in KPDM+ins. Overall, C3 was higher in KPDM-ins vs KPDM+ins at 12 months (p = 0.0081) and 24 months (p = 0.0019), while ASP was lower at baseline (p = 0.0024) and 12 months (p = 0.0281), with a decrease in ASP/C3 ratio.ConclusionsNotwithstanding greater adiposity in KPDM-ins, greater NEFA decreases and lower ASP levels during MMTT suggest better insulin and ASP sensitivity in these patients.

Cross-sectional associations of acylation stimulating protein (ASP) and adipose tissue gene expression with estradiol and progesterone in pre- and postmenopausal women.

Sex steroid hormones play an important regulatory role in fat metabolism and obesity. We hypothesized involvement of interactions between ovarian hormones with acylation stimulating protein (ASP). In 392 women with wide age (18-69years) and body size (BMI: 17 to 90kg/m(2) ) ranges, fasting plasma levels of ASP, ovarian hormones, glucose, adiponectin and lipids/apolipoproteins were assessed, along with determination of metabolic syndrome (MS) features. Gene expression of C3 (ASP precursor) and related receptors C5L2, C3aR and C5aR in subcutaneous and omental adipose tissues was measured in a subset. Acylation stimulating protein correlated negatively with concentrations of estradiol (P<0·0001), adiponectin (P<0·001) and apolipoprotein A1 (P<0·001) and positively with apolipoprotein B levels (P<0·001), systolic blood pressure (P<0·001), waist circumference (P<0·001), and triglyceride concentrations (P<0·01). In age-matched groups of lean, overweight, metabolically healthy obese (MHO) and obese with metabolic syndrome (MSO), there was a stepwise increase in ASP levels (P<0·001) while concentrations of adiponectin (P<0·0001) and estradiol (P<0·001) but not those of progesterone decreased. Progesterone but not estradiol levels correlated positively with C3 gene expression in omental adipose tissue (P<0·05) and negatively with C5L2 expression in both omental (P<0·01) and subcutaneous (P<0·05) adipose tissues. Our results are consistent with the concept that sex hormones differentially influence circulating ASP and adipose tissue gene expression of its related proteins in a depot-specific manner. ASP may play a role in the regulation of regional fat metabolism through interactions with sex hormones in women.

Acute effects of exogenous hormone administration on postprandial acylation stimulating protein levels in ovariectomized rats after a fat load.

Background. ASP, a potent lipogenic factor, was linked to female fat metabolism in association studies. Aim. To investigate acute effects of sex hormone treatment on postprandial ASP levels in vivo. Methods. 24 female rats were randomly divided into 4 groups including controls. The rats were ovariectomized and injected with progesterone, estrogen, or testosterone. An hour later, olive oil was administered orally. Plasma ASP and triglycerides were measured at several postprandial time points. Area under the curve (TG-AUC) represented TG clearance. Results. Only the progesterone treated group had a significant postprandial ASP increase at two hours compared to basal levels (439.8 ± 62.4 versus 253.4 ± 59.03 μg/mL, P = 0.04). Interestingly, increased ASP levels coordinated negatively with corresponding TG levels and TG-AUC postprandially, mostly evident in the opposite effects in the progesterone and testosterone treated groups. ASP levels increased 3-fold in the progesterone versus testosterone treated groups, whereas TG-AUC was significantly lower. Conclusion. These findings suggest that progesterone enhances ASP production and TG clearance simultaneously, supporting the notion of a stimulatory role for progesterone on ASP-mediated TG clearance. This is the first functional study demonstrating a cause-effect relationship between hormone treatment and ASP levels in vivo and may contribute to understanding the mechanism of progesterone function as a female lipogenic hormone.

Elevated Fetal Adipsin/Acylation-Stimulating Protein (ASP) in Obese Pregnancy: Novel Placental Secretion via Hofbauer Cells

Obesity in pregnancy is associated with increased risks of obesity in the offspring. We investigated the relationship between obesity in pregnancy and circulating maternal and fetal levels of adipose tissue-derived factors adipsin and acylation stimulating protein (ASP) in lean and obese mothers. Paired peripheral and cord blood samples were taken. Paired fat and placenta tissue were taken for explant culture. Media were assayed for secreted adipsin and ASP. Clinical parameters assayed included fasting insulin, glucose, and adipsin. The study was conducted at a university hospital maternity unit. Patients included 35 lean [body mass index (BMI) 19-25 kg/m(2), mean age 32 years and 39 obese (BMI) > 30 kg/m(2), mean age 32.49 years] pregnant Caucasian women, delivered by cesarean section at term. Identification of placental macrophages [Hofbauer cells (HBCs)], as a source of adipsin and ASP was determined. HBCs secreted both adipsin and ASP. Cord levels of adipsin (1663.78 ± 52.76 pg/mL) and ASP (354.48 ± 17.17 ng/mL) were significantly elevated in the offspring of obese mothers compared with their lean controls [1354.66 ± 33.87 pg/mL and 302.63 ± 14.98 ng/mL, respectively (P < .05 for both)]. Placentae from obese mothers released significantly more adipsin and ASP than placentae from lean mothers [546.0 ± 44 pg/mL · g vs 284.56 ± 43 pg/mL · g and 5485.75 ± 163.32 ng/mL · g vs 2399.16 ± 181.83 ng/mL · g, respectively (P < .05 for both)]. Circulating fetal adipsin and ASP positively correlated with maternal BMI (r = 0.611, P < .0001, and r = 0.391, P < .05, respectively). Fetal adipsin correlated positively with maternal (r = 0.482, P < .01) and fetal homeostasis model assessment of insulin resistance (r = 0.465, P < .01). We demonstrate novel secretion of adipsin and ASP by placental HBCs.

Obesity-inducing diet promotes acylation stimulating protein resistance

Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system that is involved in energy homeostasis and inflammation. ASP acts on and correlates positively with postprandial fat clearance in healthy subjects. However, in obesity, ASP levels are elevated and correlate inversely with fat clearance, indicative of a potential resistance to ASP. Using a mouse model, we hypothesized that, over time, diet-induced obesity (DIO) would result in development of ASP insensitivity, as compared to chow-fed animals as controls. Injection of recombinant ASP in DIO mice failed to accelerate fat clearance to the same extent as in chow-fed mice. DIO mice exhibited higher basal levels of plasma ASP and, after 30weeks of diet, showed lower ASP receptor (C5L2) expression in adipose tissue compared to chow-fed mice. Additionally, ex vivo ASP stimulation failed to induce normal Ser473AKT phosphorylation in adipose tissue from DIO mice VS chow-fed controls. These results demonstrate for the first time a state of diet-induced ASP resistance. Changes in the ASP-C5L2 pathway dynamics in obesity could alter the development of obesity and co-morbidities such as atherosclerosis and type 2 diabetes.

Increased acylation stimulating protein levels in young obese males is correlated with systemic markers of oxidative stress

As little is known about relationship between acylation stimulating protein (ASP) and oxidative stress, whether there is any link between ASP and oxidative stress in young obese males were investigated. Forty-five obese (median body mass index (BMI) = 36.99 (IQR = 3.65) kg m(-2)) male subjects (median age = 22 (IQR = 6) years) and 24 age-matched (median age = 22.5 (IQR = 4.8) years) healthy male volunteers (median body mass index (BMI) = 23.67 (IQR = 2.45) kg m(-2)) were recruited into the study. All obese subjects have BMI > 30 kg m(-2), while all controls have BMI < 25 kg m(-2). Fasting plasma ASP, lipid hydroperoxide, high sensitivity C-reactive protein (hs-CRP), fasting insulin, triglyceride, LDL-cholesterol levels and HOMA-IR were higher, whereas the mean HDL-cholesterol levels and glutathione peroxidase (GPx) enzyme activity were significantly lower in obese subjects than controls. The linear regression analysis showed that lipid hydroperoxide was independently associated with only BMI, while ASP was independently associated with BMI and triglyceride. The present data support the concept that obesity occurs under condition of compex interactions by adipokines, insulin, inflammation, and oxidative stress.

Plasma Levels of Acylation-Stimulating Protein Are Strongly Predicted by Waist/Hip Ratio and Correlate with Decreased LDL Size in Men

The association of abdominal obesity with cardiovascular risk is often linked to altered secretion of adipose-derived factors and an abnormal lipid profile including formation of atherogenic small dense low density lipoprotein particles (sdLDL). Acylation-stimulating protein (ASP) is an adipose-derived hormone that exhibits potent lipogenic effects. Plasma ASP levels increase in obesity; however, the association of ASP levels with body fat distribution is not yet established, and no study to date has investigated the association of ASP with LDL size. In this study, we examined the association of ASP levels with abdominal obesity measures and the lipid profile including LDL size in 83 men with a wide range of abdominal girths. Regression analysis showed that waist/hip ratio was the main predictor of ASP levels (β = 0.52, P < 0.0001), significantly followed by decreased LDL size. BMI and TG levels, although positively correlated with ASP levels, were excluded as significant predictors in regression analysis. No correlation was found with LDL-C or apoB levels. ASP levels were 62.5% higher in abdominally obese compared to nonobese men. Waist/hip ratio presenting as the main predictor of ASP levels, suggests increased ASP production by abdominal fat which, as proposed previously, may result from resistance to ASP function causing delayed TG clearance and subsequent formation of atherogenic sdLDL.