Acylation Stimulating Protein Research Articles

Relationship between a novel polymorphism of C5L2 gene and coronary artery disease in Chinese Han and Uyghur population

BackgroundC5L2 was demonstrated a functional receptor of acylation-stimul- ating protein (ASP) which is a stimulator of either triglyceride synthesis or glucose transport. However, little is known about the variations in...

Relationship between a novel polymorphism of the C5L2 gene and coronary artery disease

BackgroundC5L2 has been demonstrated to be a functional receptor of acylation-stimulating protein (ASP), which is a stimulator of triglyceride synthesis or glucose transport. However, little is known about the variations...

Adipose Tissue Gene Expression of Factors Related to Lipid Processing in Obesity

BackgroundAdipose tissue lipid storage and processing capacity can be a key factor for obesity-related metabolic disorders such as insulin resistance and diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim of this study was to analyze the gene expression of factors involved in lipid uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue according to body mass index (BMI) and the degree of insulin resistance (IR).Methods and Principal FindingsVLDL receptor (VLDLR), lipoprotein lipase (LPL), acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR, 10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean controls. In SAT, LPL and FABP4 expression were also higher in lean controls. BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple regression analysis showed that BMI was the main variable contributing to LPL and FABP4 gene expression in both VAT and SAT.ConclusionsMorbidly obese patients have a lower gene expression of factors related with lipid uptake and processing in comparison with healthy lean persons.

CD55 Deficiency Protects against Atherosclerosis in ApoE-Deficient Mice via C3a Modulation of Lipid Metabolism

Atherosclerosis, the leading cause of death in the Western world, is driven by chronic inflammation within the artery wall. Elements of the complement cascade are implicated in the pathogenesis, because complement proteins and their activation products are found in the atherosclerotic plaque. We examined the role of CD55, a membrane inhibitor of the complement component 3 (C3) convertase, which converts C3 into C3a and C3b, in atherosclerosis. CD55-deficient (CD55−/−) mice were crossed onto the atherosclerosis-prone apolipoprotein E (apoE)-deficient (apoE−/−) background. High fat–fed male apoE−/−/CD55−/− mice were strongly protected from developing atherosclerosis compared with apoE−/− controls. Lipid profiling showed significantly lower levels of triglycerides, nonesterified fatty acids, and cholesterol in apoE−/−/CD55−/− mice than that in controls after high-fat feeding, whereas body fat in apoE−/−/CD55−/− mice content was increased. Plasma levels of C3 fell, whereas concentrations of C3adesArg (alias acylation stimulating protein; ASP), produced by serum carboxypeptidase N–mediated desargination of C3a, increased in nonfasted high fat–fed apoE−/−/CD55−/− mice, indicating complement activation. Thus, complement dysregulation in the absence of CD55 provoked increased C3adesArg production that, in turn, caused altered lipid handling, resulting in atheroprotection and increased adiposity. Interventions that target complement activation in adipose tissue should be explored as lipid-decreasing strategies.

Relationship between a Novel Polymorphism of the C5L2 Gene and Coronary Artery Disease

BackgroundC5L2 has been demonstrated to be a functional receptor of acylation-stimulating protein (ASP), which is a stimulator of triglyceride synthesis or glucose transport. However, little is known about the variations in the coding region of the C5L2 gene and their association with coronary artery disease (CAD).Methodology/Principal FindingsWe identified a novel single nucleotide polymorphism (SNP), 698C>T (P233L), in exon 2 using a polymerase chain reaction direct-sequencing method. This nucleotide change causes the amino-acid order from proline to leucine at codon 233. We examined the role of this SNP for CAD using two independent case–control studies: one was in the Han population (492 CAD patients and 577 control subjects) and the other was in the Uygur population (319 CAD patients and 554 control subjects). Heterozygote carriers of the 698CT genotype were more frequent among CAD patients than among controls not only in the Han population (7.3% versus 1.7%) but also in the Uygur population (4.7% versus 1.6%). The odds ratio (OR) for carriers of the 698CT genotype for CAD was 4.484 (95% confidence interval (CI): 2.197–9.174) in the Han group and 2.989 (95% CI: 1.292–6.909) in the Uygur population. After adjustment of confounding factors such as sex, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, high-density lipoprotein, the difference remained significant in the Han group (P<0.001, OR = 6.604, 95% CI: 2.776–15.711) and in the Uygur group (P = 0.047, OR = 2.602, 95% CI: 1.015–6.671).Conclusion/SignificanceThe 698CT genotype of C5L2 may be a genetic maker of CAD in the Han and Uygur population in western China.

Plasma Adipokine and Hormone Changes in Mountaineers on Ascent to 5300 Meters

The current study evaluated multiple metabolic and inflammatory hormone responses in recreational climbers (7 men and 3 women, age 26-49 years) over 9 days. In particular, acylation-stimulating protein (ASP), which influences fat storage in adipose tissue, has not been measured at high altitude. Serial measurements were taken at sea level (SL), or 353 m, on day 0, 4000 m on day 3, 4750 m on day 6, and 5300 m on day 9 of the expedition. Body mass index (BMI) decreased upon ascent to 5300 m from SL (SL 23.2 ± 1.5 kg/m(2); 4000 m 23.2 ± 1.4 kg/m(2); 4750 m 22.9 ± 1.3 kg/m(2); 5300 m 22.3 ± 1.2 kg/m(2); P<.001). Similarly, plasma non-esterified fatty acids and triglycerides increased, while HDL cholesterol decreased (P<.05 to <.001) from SL to 5300 m. Acylation-stimulating protein (SL 42.2 ± 40.2 nm; 4000 m 117.0 ± 69.6 nm; 4750 m 107.9 ± 44.5 nm; 5300 m 82.2 ± 20.2 nm; P=.019) and adiponectin (SL 10.4 ± 6.5 ng/mL, 4000 m 13.9 ± 8.5 ng/mL, 4750 m 18.3 ± 8.3 ng/mL, 5300 m 14.7 ± 8.0 ng/mL; P=.015) increased, as did insulin and Interleukin-6 (IL-6) levels (up to 71% and 168%, respectively; P<.05) with no change in leptin, complement C3 (C3), high sensitivity C-reactive protein (hsCRP) or cortisol levels throughout the mountain ascent from SL to 5300 m. Acylation-stimulating protein and adiponectin are increased during a 9-day period of high altitude (SL to 5300 m) exposure despite weight loss in healthy mountaineers.

Récentes adipokines : un lien entre l’obésité et l’athérosclérose

Today, cardiovascular diseases (CVD) remain the principal cause of death in industrialized countries and are linked to obesity and metabolic syndrome. Metabolic syndrome is characterized by changes in arterial blood pressure, glucose metabolism, lipid and lipoprotein profiles in addition to inflammation. Adipose tissue produces many cytokines and secretory factors termed adipokines. Intra-abdominal (visceral) adipose tissue in particular, rather than peripheral, appears to be associated with global cardiometabolic risk. The present article summarizes information on five recently discovered adipokines: vaspin, visfatin, apelin, acylation stimulating protein (ASP) and retinol-binding protein 4 (RBP4) and their potential beneficial or deleterious roles in obesity and atherosclerosis. Vaspin may have antiatherogenic effects through its potential insulin-sensitizing properties. Similarly, visfatin has been suggested to enhance insulin sensitivity, but its potential role in plaque destabilization may counteract this. Apelin, via inhibition of food intake, and increases in physical activity and body temperature, may promote weight loss, resulting in a beneficial antiatherogenic effect. Further, favourable effects on vasodilatation and blood pressure add to this positive effect. Considering its increased levels in subjects with demonstrated atherosclerosis, RBP4 may constitute a biomarker. Lastly, ASP, often increased in obesity and metabolic disorders, may be contributing to efficient lipid storage, and decreasing or blocking ASP may provide a potential antiobesity target. Adipokines may further contribute to obesity-atherosclerosis relationships, the full understanding of which will require further research.

Acute injection of ASP in the third ventricle inhibits food intake and locomotor activity in rats

Acylation-stimulating protein (ASP; also known as C3adesArg) stimulates triglyceride synthesis and glucose transport via interaction with its receptor C5L2, which is expressed peripherally (adipose tissue, muscle) and centrally. Previous studies have shown that ASP-deficient mice (C3KO) and C5L2-deficient mice (C5L2KO) are hyperphagic (59 to 229% increase, P < 0.0001), which is counterbalanced by increased energy expenditure measured as oxygen consumption (Vo(2)) and a lower RQ. The aim of the present study was to evaluate ASP's effect on food intake, energy expenditure, and neuropeptide expression. Male rats were surgically implanted with intracerebroventricular (icv) cannulas directed toward the third ventricle. After a 5-h fast, rats were injected, and food intake was assessed at 0.5, 1, 2, 4, 16, 24, and 48 h, with a 5- to 7-day washout period between each injection. Acute icv injections of ASP (0.3-1,065 pmol) had a time-dependent effect on decreasing food intake by 20 to 57% (P < 0.05). Decreases were detected by 30 min (maximum 57%, P < 0.01) and at the highest dose effects extended to 48 h (19%, P < 0.05, 24- to 48-h period). Daily body weight gain was decreased by 131% over the first 24 h and 29% over the second 24 h (P < 0.05). A conditioned taste aversion test indicated that there was no malaise. Furthermore, acute ASP injection affected energy substrate usage, demonstrated by decreased Vo(2) and RQ (P < 0.05; implicating greater fatty acid usage), with a 49% decrease in total activity over 24 h (P < 0.05). ASP administration also increased anorexic neuropeptide POMC expression (44%) in the arcuate nucleus, with no change in NPY. Altogether ASP may have central in addition to peripheral effects.

The molecular mechanism of acylation stimulating protein regulation of adipophilin and perilipin expression: Involvement of phosphoinositide 3-kinase and phospholipase C

The novel adipokine acylation stimulating protein (ASP) is involved in lipid metabolism and obesity-related disorders. Adipophilin and perilipin, two members of the lipid droplet protein family, participate not only in fat storage within adipocytes, but also in ectopic lipid deposition in the form of cytoplasmic triglyceride (TG) droplets within many types of mammalian cells. During differentiation to mature adipocytes, mechanisms controlling the synthesis and turnover of these lipid droplet proteins are only partially understood, the mechanisms regulating gene/protein expression as yet unidentified. In our previous study, ASP has been shown to regulate adipophilin and perilipin expression to facilitate TG synthesis during 3T3-L1 cell differentiation. Our aim in this study was to provide insight into the physiological importance of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) in ASP-triggered alteration of adipophilin and perilipin expression. We found that acute (2.5 h) inhibition of PLC or PI3K results in a decrease in mRNA and protein of perilipin and adipophilin at any time during differentiation. The fact that there is such a rapid change even with mRNA levels suggests a rapid turnover of both mRNA and protein independent of a direct ASP effect. Also, the presence of these inhibitors blocked the ASP stimulatory effects with a maximal decrease in gene and protein expression of adipophilin (-45% and -60%, respectively, P < 0.01) and perilipin (-96% and -63%, respectively, P < 0.01 and P < 0.05). These findings provide further understanding of the adipogenic properties of ASP in adipocytes.

Abnormal Adipokines Associated with Various Types of Obesity in Chinese Children and Adolescents

Objective To explore the role of adipokines including insulin, resistin, leptin, adiponectin, acylation stimulating protein (ASP) and complement C3 (C3) in various types of obesity (peripheral obesity, abdominal obesity and mixed obesity) in Chinese children and adolescents, and their relationships with body size and pubertal development. Methods Children and adolescents ( n=3 508) aged 6 to 18 years, with 1 788 boys and 1 720 girls were assessed for body mass index, waist circumference, pubertal development, blood insulin, resistin, leptin, adiponectin, ASP and C3 levels. Three types of obesity [peripheral obesity ( n=43), abdominal obesity ( n=473), mixed obesity ( n=1 187)] and non-obese control ( n=1 805) were defined with combined use of Chinese body mass index and waist circumference criteria. Results Serum resistin, leptin and adiponectin levels were higher in girls than those in boys (all P<0.01). Insulin and leptin increased and adiponectin decreased across five Tanner stages in both girls and boys (all P<0.001), while ASP changed only in girls ( P<0.001) and C3 only in boys ( P<0.001). Insulin, leptin and ASP were higher, but adiponectin was lower in all three types of obesity vs. the non-obese control (all P<0.05). The greatest abnormalities of all six adipokines were found in the mixed obesity group. With inclusion of body mass index and waist circumference in simultaneous regression analyses, both body size indices were independently and significantly correlated with insulin, leptin and adiponectin after age and gender adjustment. Compared with waist circumference, the body mass index was stronger in interpreting insulin, leptin, adiponectin and ASP levels, whereas it was weaker in explaining variance of plasma C3. Conclusion Obese children have a worse metabolic profile with high insulin, resistin, leptin, ASP and C3, and low adiponectin levels. The adipokine profile in mixed obesity is worse than that in peripheral or abdominal obesity. Identification of obese subjects with a malignant adipokine profile using a combination of body mass index and waist circumference is important for the prevention of obesity-related disease.

Acylation stimulating protein: a female lipogenic factor?

Acylation stimulating protein (ASP) is a potent lipogenic factor produced from adipocytes. Plasma ASP levels were shown to increase in obesity, diabetes mellitus type II and dyslipidemia, and decrease after weight loss and fasting. Growing evidence suggests that ASP may significantly contribute to subcutaneous fat storage in females. In vitro, ASP stimulated triglyceride synthesis to a larger extent in subcutaneous compared with omental adipocytes. The ASP receptor binding affinity to plasma membranes prepared from adipose tissue showed higher binding affinity to plasma membranes from female adipose tissue compared with male adipose tissue, and was more pronounced to subcutaneous compared with omental plasma membranes. Human studies demonstrated that postprandial triglyceride clearance predicted by ASP levels was more efficient in women than in men. In mice, postprandial triglyceride clearance, with intraperitoneal ASP administration, was faster in females compared with males. The ASP deficient mice were resistant to weight gain and had reduced fat mass that was more pronounced in females. Recent findings in humans and mice point to a significant association between progesterone and ASP variations in females. In this review, we highlight findings, to date, linking ASP to physiological and hormonal alterations that may contribute to subcutaneous fat distribution typical to females.

Evaluation of chylomicron effect on ASP production in 3T3-L1 adipocytes

In the past few years, there has been increasing interest in the production and physiological role of acylation-stimulating protein (ASP), identical to C3adesArg, a product of the alternative complement pathway generated through C3 cleavage. Recent studies in C3 (-/-) mice that are ASP deficient have demonstrated a role for ASP in postprandial triglyceride clearance and fat storage. The aim of the present study was to establish a cell model and sensitive ELISA assay for the evaluation of ASP production using 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated into adipocytes, then cultured in different media such as serum-free (SF), Dulbecco's modified Eagle's medium (DMEM)/F12 + 10% fetal calf serum (FBS), and at varying concentrations of chylomicrons and insulin + chylomicrons up to 48 h. ASP production in SF and DMEM/F12 + 10% FBS was compared. Chylomicrons stimulated ASP production in a concentration- and time-dependent manner. By contrast, chylomicron treatment had no effect on the production of C3, the precursor protein of ASP, which was constant over 48 h. Addition of insulin (100 nM) to a low-dose of chylomicrons (100 µg TG/ml) significantly increased ASP production compared with chylomicrons alone at 48 h (P < 0.001). Furthermore, addition of insulin significantly increased C3 secretion at both 18 and 48 h of incubation (P < 0.05, P < 0.001, respectively). Overall, the proportion of ASP to C3 remained constant, indicating no change in the ratio of C3 cleaved to generate ASP. This study demonstrated that 3T3-L1 adipocyte is a useful model for the evaluation of C3 secretion and ASP production by using a sensitive mouse-specific ELISA assay. The stimulation of ASP production with chylomicrons demonstrates a physiologically relevant response, and provides a strategy for further studies on ASP production and function.

The beta-1 adrenergic antagonist, atenolol, decreases acylation stimulating protein, exercise capacity and plasma free fatty acids in men with type 2 diabetes

Background and aimsAtenolol is a beta-1 adrenergic antagonist commonly prescribed for the treatment of systemic hypertension or coronary artery disease yet its use in individuals with type 2 diabetes mellitus (T2DM) is controversial due to potentially negative side effects on insulin resistance. Non-esterified fatty acid (NEFA) metabolism is altered in T2DM especially under conditions of metabolic stress such as exercise or the postprandial state. We evaluated atenolol effects on circulating NEFA and related hormones in men with T2DM during acute cardiorespiratory exercise in both the fasting and postprandial state, including the adipokine acylation stimulating protein (ASP) which stimulates adipose tissue NEFA uptake. Methods and resultsTen men with T2DM underwent four 1-h exercise sessions at 60% of their maximal oxygen uptake (VO2max) under the following conditions: 1) fasting (F), and 2) 2 h postprandial (PP) without medication; and 3) fasting (F-Atenolol), and 4) 2 h postprandial (PP-Atenolol) after a one-week treatment with atenolol. Results were tested for the effects of atenolol via two-way ANOVA for the F vs F-Atenolol and PP vs PP-Atenolol states separately. Atenolol treatment decreased fasting and postprandial glycerol (p < 0.0001) and NEFA (p < 0.0001), postprandial epinephrine (p = 0.048), postprandial cortisol (p = 0.02), postprandial ASP (p = 0.04) and postprandial dopamine (p < 0.004). ConclusionAtenolol alters fatty acid metabolism and associated metabolic hormones including ASP during exercise in men with T2DM and its effects are more apparent during conditions of stress such as the postprandial state, acute exercise and obesity.

S323I polymorphism of the C5L2 gene was not identified in a Chinese population with familial combined hyperlipidemia or with type 2 diabetes

C5L2, a G protein-coupled receptor, is known to be a functional receptor of acylation-stimulating protein, which is a stimulator of triglyceride synthesis and glucose transport. A novel C5L2 variant (S323I) was identified and its association with familial combined hyperlipidemia (FCH) was recently reported. We looked for this SNP in three Chinese ethnic groups, including Han, Uygur, and Kazakh controls and patients with FCH and type 2 diabetes. One hundred and eighty-two unrelated subjects (77 of Han, 57 of Uygur, and 48 of Kazakh) with FCH were genotyped by direct sequencing, and 852 subjects (342 of Han, 338 of Uygur, 172 of Kazakh) with type 2 diabetes and 200 healthy controls (67 of Han, 72 of Uygur, and 61 of Kazakh) chosen from a cardiovascular risk survey study were genotyped with PCR-RFLP analysis. All 182 subjects with FCH, 99.5% of the type 2 diabetes patients and 100% of the healthy controls were successfully genotyped. Neither the FCH subjects nor the type 2 diabetes patients were found to have the S323I variant. This variant was also not identified in the healthy controls. We found no evidence to demonstrate that the S323I polymorphism contributes to familial combined hyperlipidemia or type 2 diabetes in the Chinese population.

POTENTIAL MARKERS OF INSULIN RESISTANCE IN HEALTHY VS OBESE AND OVERWEIGHT SUBJECTS

Insulin resistance can lead to the metabolic syndrome, which may have cardiovascular and metabolic consequences. The study aimed at verifying the serum concentration levels of the adipose tissue proteins adiponectin, adipocyte-fatty acid binding protein (a-FABP) and acylation stimulating protein (ASP), and the potential use of these markers for early diagnosis of insulin resistance. Healthy subjects (Group A, n = 53), overweight subjects (Group B, n = 29) and obese subjects (Group C, n = 51) were studied. Those in Groups B and C had symptoms of insulin resistance. The subjects were selected based on clinical and laboratory findings. The concentrations of adiponectin were highest in the healthy subjects in Group A (14.18 ± 6.99 mg/), lower in the overweight subjects in Group B (11.12 ± 4.46 mg/l) and lowest in the obese subjects in Group C (8.15 ± 2.70 mg/l). The a-FABP values were lowest in Group A (20.23 ± 7.95 mg/l), higher in Group B (32.22 ± 15.56 mg/l) and highest in Group C (40.43 ± 23.31 mg/l). The concentrations of ASP were lowest in the Group A healthy subjects (43.01 ± 22.78 nmol/l), higher in the Group B overweight subjects (50.58 ± 25.57 nmol/l) and highest in the Group C obese subjects (54.70 ± 26.41 nmol/l). Statistically significant correlation coefficients in subjects from all groups among the markers studied describe the highest correlation is between a-FABP and BMI (r = 0.48), adiponectin and QUICKI (r = 0.42), adiponectin and triacylglycerols (r = -0.35), ASP and BMI (r = 0.33) and adiponectin and BMI (r = -0.31). The concentrations of all studied markers were different in the healthy subjects as compared to the overweight or obese ones. Adiponectin proved to be a good indicator of insulin sensitivity, the low concentration of which could signal the initial stage of insulin resistance. A-FABP proved to be a prominent marker of "adiposity" in association with the development of insulin resistance. ASP did not prove to show significant differences between the overweight and healthy subjects, but significant differences were found between the obese and healthy subject.

Key role of CD14 in the E. coli- and LPS-induced mRNA down regulation of the C5a receptors CD88 and C5L2

Recent studies suggested that the immunometabolic receptors; C5aR and C5L2, constitutively self-associate into homo-/heterodimers and that acylation stimulating protein (ASP/C3adesArg) or C5a treatment of adipocytes increased their colocalization. The present study evaluates the C5aR contribution in adipocytes to the metabolic and immune responses elicited by ligand stimulation.The effects of C5a, ASP, and insulin on cytokine production, triglyceride synthesis (TGS), and key signaling pathways were evaluated in isolated primary adipocytes and cultured 3T3-L1 differentiated adipocytes. In addition, mRNA expression of IRS1 and PGC1α was compared in adipose tissue samples from WT vs. C5aRKO mice.Both C5a and ASP directly increased MCP-1 (238 ± 4%; P < 0.001, and 377 ± 2% vs. basal 100%; P < 0.001, respectively) and KC (413 ± 11%; P < 0.001, and 529 ± 16%; P < 0.001 vs. basal 100%, respectively) secretion, TGS (131 ± 1%; P < 0.001, and 152 ± 6%; P < 0.001, vs. basal 100% respectively), and Akt/NFκB phosphorylation pathways in adipocytes. However, in C5aRKO adipocytes, C5a effects were disrupted, while stimulatory effects of ASP were mostly maintained. Addition of C5a completely blocked ASP signaling and activity in both C5aRKO and WT adipocytes as well as 3T3-L1 adipocytes. Furthermore, C5aRKO adipocytes revealed impaired insulin stimulation of cytokine production, with partial impairment of signaling and TGS stimulation, consistent with decreased IRS1 and PGC1α mRNA expression in adipose tissue.These observations indicate the importance of C5aR in adipose tissue metabolism and immunity, which may be regulated through heterodimerization with C5L2.

The ASP and C5L2 pathway: another bridge between inflammation and metabolic homeostasis

Hormones secreted from the adipose tissue, termed adipokines, have been extensively studied in the past two decades and this work has triggered a paradigm shift. Previously considered to be a passive organ exclusively devoted to storage, adipose tissue is now seen as a major endocrine modulator of energy homeostasis. Acylation-stimulating protein (ASP) is one of these adipokines and it interacts with its receptor C5L2 to induce several anabolic effects. Both ASP and C5L2 are also closely linked with the immune system. However, few studies have examined the duality of roles observed with ASP and C5L2. This article aims to demonstrate the potential roles of ASP and C5L2 in metabolic homeostasis and inflammation and to discuss the relationships of these two parallel systems.

Growth patterns during childhood and the relationship with acylation‐stimulating protein

Acylation-stimulating protein (ASP) is an adipose tissue-derived hormone, which stimulates glucose and free fatty acid (FFA) uptake into adipocytes. Changes in ASP metabolism are associated with alterations in lipid metabolism. As postnatal catch-up growth has been associated with dyslipidaemia in later life, we investigated the association between ASP and birth size, adult size and different growth patterns during childhood. The associations were investigated by multiple regression analyses in 285 young adults, aged 18-24. Subsequently, differences in ASP were analysed in four clinically relevant subgroups, young adults either born small for gestational age with short stature (SGA-S) or with catch-up growth (SGA-CU), or born appropriate for gestational age with idiopathic short stature (ISS) or with normal stature (controls). Weight gain during childhood, particularly fat accumulation, was positively related to ASP levels in early adulthood, independent of birth size, age and gender. Foetal growth, reflected by birth size, was not related to ASP levels. Between the subgroups, no differences in ASP were found, but SGA-CU and ISS subjects had significantly higher levels of FFA. Exaggerated weight gain during childhood, but not foetal growth, contributes to alterations in ASP metabolism, which may be associated with impaired FFA uptake and delayed triglycerides clearance. Therefore, exaggerated weight gain during childhood should be prevented.

The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice

BackgroundAcylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure.ResultsIn mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P < 0.05) while Anti-ASP neutralized the rASP response. Mice treated with Anti-ASP showed elevated energy expenditure (P < 0.0001), increased skeletal muscle glucose oxidation (+141%, P < 0.001), reduced liver glycogen (-34%, P < 0.05) and glucose-6-phosphate content (-64%, P = 0.08) compared to control mice. There was no change in body weight, food intake, fasting insulin, adiponectin, CRP or TG levels compared to controls. Interestingly, HFD mice treated with rASP showed the opposite phenotype with reduced energy expenditure (P < 0.0001) and increased body weight (P < 0.05), cumulative food intake (P < 0.0001) and liver glycogen content (+59%, P < 0.05). Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).ConclusionIn vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

Cardiovascular and Metabolic Risk Profile and Acylation-Stimulating Protein Levels in Children with Prader-Willi Syndrome and Effects of Growth Hormone Treatment

Cardiovascular and Metabolic Risk Profile and Acylation-Stimulating Protein Levels in Children with Prader-Willi Syndrome and Effects of Growth Hormone Treatment