Lower Zinc-α2-Glycoprotein Production by Adipose Tissue and Liver in Obese Patients Unrelated to Insulin Resistance

Context: Zinc-α2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays. Objective: The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored. Design: This was a case-control study. Setting: The study was conducted at a university referral center. Patients and Methods: Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures. Results: Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 ± 10.45 vs. 63.26 ± 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = −0.65, P < 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = −0.68, P < 0.001) and VAT were detected (r = −0.64, P < 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro. Conclusion: A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance. A downregulation of zinc-α2 glycoprotein in adipose tissue and liver exists in obese patients, and it is unrelated to insulin resistance.

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Influence of Obesity in the miRNome: miR-4454, a Key Regulator of Insulin Response Via Splicing Modulation in Prostate

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa580 ◽

2020 ◽

Author(s):

Vicente Herrero-Aguayo ◽

Juan M Jiménez-Vacas ◽

Prudencio Sáez-Martínez ◽

Enrique Gómez-Gómez ◽

Juan L López-Cánovas ◽

...

Keyword(s):

Insulin Resistance ◽

Body Mass Index ◽

Body Mass ◽

Dependent Manner ◽

Model Assessment ◽

Major Health Problem ◽

Altered Expression ◽

Mirna Array ◽

Obese Subjects

Abstract Context Obesity is a major health problem associated with severe comorbidities, including type 2 diabetes and cancer, wherein microRNAs (miRNAs) might be useful as diagnostic/prognostic tools or therapeutic targets. Objective To explore the differential expression pattern of miRNAs in obesity and their putative role in obesity-related comorbidities such as insulin resistance. Methods An Affymetrix-miRNA array was performed in plasma samples from normoweight (n = 4/body mass index < 25) and obese subjects (n = 4/body mass index > 30). The main changes were validated in 2 independent cohorts (n = 221/n = 18). Additionally, in silico approaches were performed and in vitro assays applied in tissue samples and prostate (RWPE-1) and liver (HepG2) cell-lines. Results A total of 26 microRNAs were altered (P < 0.01) in plasma of obese subjects compared to controls using the Affymetrix-miRNA array. Validation in ampler cohorts revealed that miR-4454 levels were consistently higher in obesity, associated with insulin-resistance (Homeostatic Model Assessment of Insulin Resistance/insulin) and modulated by medical (metformin/statins) and surgical (bariatric surgery) strategies. miR-4454 was highly expressed in prostate and liver tissues and its expression was increased in prostate and liver cells by insulin. In vitro, overexpression of miR-4454 in prostate cells resulted in decreased expression levels of INSR, GLUT4, and phosphorylation of AMPK/AKT/ERK, as well as in altered expression of key spliceosome components (ESRP1/ESRP2/RBM45/RNU2) and insulin-receptor splicing variants. Conclusions Obesity was associated to an alteration of the plasmatic miRNA landscape, wherein miR-4454 levels were higher, associated with insulin-resistance and modulated by obesity-controlling interventions. Insulin regulated miR-4454, which, in turn may impair the cellular response to insulin, in a cell type-dependent manner (i.e., prostate gland), by modulating the splicing process.

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Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance

Acta Endocrinologica ◽

10.1530/eje.0.1490331 ◽

2003 ◽

Vol 149 (4) ◽

pp. 331-335 ◽

Cited By ~ 350

Author(s):

JV Silha ◽

M Krsek ◽

JV Skrha ◽

P Sucharda ◽

BL Nyomba ◽

...

Keyword(s):

Insulin Resistance ◽

Body Mass Index ◽

Adipose Tissue ◽

Statistical Significance ◽

Model Assessment ◽

Fasting Insulin ◽

Homeostasis Model Assessment ◽

Glucose Levels ◽

Obese Subjects ◽

The Relationship

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.

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Ultra-Early and Early Changes in Bile Acids and Insulin after Sleeve Gastrectomy among Obese Patients

Medicina ◽

10.3390/medicina55120757 ◽

2019 ◽

Vol 55 (12) ◽

pp. 757

Author(s):

Adriana Florinela Cӑtoi ◽

Alina Elena Pârvu ◽

Aurel Mironiuc ◽

Horațiu Silaghi ◽

Ioana Delia Pop ◽

...

Keyword(s):

Insulin Resistance ◽

Body Mass Index ◽

Sleeve Gastrectomy ◽

Model Assessment ◽

Obese Patients ◽

Fasting Insulin ◽

Homeostasis Model Assessment ◽

Insulin Homeostasis ◽

Obese Subjects ◽

Time Point

Background and Objective: In obese patients, sleeve gastrectomy (SG) has shown mixed results on bile acid (BA) values. The aim of our study was to examine the potential ultra-early and early changes of the circulating total BA in relation with the changes of insulin resistance (IR) in obese patients submitted to laparoscopic SG. Materials and Methods: Twenty-four obese subjects were investigated for body mass index (BMI), total fasting BA, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and leptin before and at 7 and 30 d after SG. Results: After surgery, mean BMI decreased at the first (p < 0.001) and at the second time point (p < 0.001) relative to baseline. Total fasting BA values did not change significantly at 7 d (p = 0.938) and at 30 d (p = 0.289) after SG. No significant changes were found at 7 d (p = 0.194, p = 0.34) and 30 d (p = 0.329, p = 0.151) after surgery regarding fasting insulin and HOMA-IR, respectively. However, a trend of increased total fasting BA and decreased fasting insulin and HOMA- after laparoscopic SG has been found. Negative correlations between total fasting BA and insulin (r = −0.807, p = 0.009), HOMA-IR (r = −0.855, p = 0.014), and blood glucose (r = −0.761, p = 0.047), respectively, were observed at one month after SG. Conclusion: In conclusion, here, we found a lack of significant changes in total fasting BA, insulin, and HOMA-IR ultra-early and early after SG, which precluded us to consider a possible relation between the variations of BA and IR. However, the presence of the tendency for total fasting BA to increase and for insulin and HOMA-IR to decrease, as well as of the negative correlations one month after laparoscopic SG, suggest that this surgery brings about some changes that point towards the existence, and possibly towards the restoration, at least to some extent, of the link between BA and glucose metabolism.

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Elevated β2-adrenoceptor protein concentration in adipose tissue from obese subjects is closely related to the body mass index and waist/hip ratio

Clinical Science ◽

10.1042/cs1040093 ◽

2003 ◽

Vol 104 (2) ◽

pp. 93-102 ◽

Cited By ~ 2

Author(s):

Mads RASMUSSEN ◽

Thomas ALMDAL ◽

Palle BRATHOLM ◽

Niels Juel CHRISTENSEN

Keyword(s):

Body Mass Index ◽

Adipose Tissue ◽

Body Mass ◽

Protein Concentration ◽

The Body ◽

Receptor Protein ◽

Mrna Levels ◽

Membrane Area ◽

Waist Hip Ratio ◽

Obese Subjects

The aim of the present study was to quantify β2-adrenoceptor protein content in adipose tissue during fasting, and to study the relationships between β2-adrenoceptor protein and mRNA levels and changes in metabolites related to lipolysis. Groups of male subjects with a body mass index of <25kg/m2 or >30kg/m2 fasted for 60h. Abdominal subcutaneous fat biopsies were analysed for receptor mRNA levels by reverse transcription–PCR–HPLC. The β2-adrenoceptor protein concentration was measured by Western blotting using fluorescence laser scanning for detection. The β2-adrenoceptor protein concentration per cell (on a DNA basis) was higher in obese subjects (P<0.03). There were highly significant relationships between β2-adrenoceptor protein concentration and both body mass index and waist/hip ratio (P<0.001 for both). Furthermore, there was an inverse relationship between the receptor protein concentration and the serum β-hydroxybutyrate level during fasting (P<0.005). β2-Adrenoceptor protein levels decreased in both groups during fasting, to a similar degree. Basal β2-adrenoceptor mRNA levels were similar in the two groups, but there was a smaller increase in the obese group during fasting (P<0.03). The increased β2-adrenoceptor protein level in obese subjects is likely to be related to the greater plasma membrane area of their adipocytes. The decrease during fasting may be due to increased binding of noradrenaline and subsequent internalization and degradation of the receptor. Elevated levels of less responsive β2-adrenoceptor protein in obese subjects may contribute to the development of obesity.

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Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways

Thrombosis and Haemostasis ◽

10.1160/th14-06-0506 ◽

2015 ◽

Vol 113 (04) ◽

pp. 838-850 ◽

Cited By ~ 20

Author(s):

Alessandra Quercioli ◽

Fabienne Burger ◽

Aurélien Thomas ◽

Estelle Lauer ◽

Analina Raquel da Silva ◽

...

Keyword(s):

Gastric Bypass ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

University Hospital ◽

Control Group ◽

Obese Patients ◽

Cc Chemokines ◽

Obese Subjects ◽

Morbid Obese

SummaryParadoxically, morbid obesity was suggested to protect from cardiovascular co-morbidities as compared to overweight/obese patients. We hypothesise that this paradox could be inferred to modulation ofthe “endocannabinoid” system on systemic and subcutaneous adipose tissue (SAT) inflammation. We designed a translational project including clinical and in vitro studies at Geneva University Hospital. Morbid obese subjects (n=11) were submitted to gastric bypass surgery (GBS) and followed up for one year (post-GBS). Insulin resistance and circulating and SAT levels of endocannabinoids, adipocytokines and CC chemokines were assessed pre- and post-GBS and compared to a control group of normal and overweight subjects (CTL) (n=20). In vitro cultures with 3T3-L1 adipocytes were used to validate findings from clinical results. Morbid obese subjects had baseline lower insulin sensitivity and higher hs-CRP, leptin, CCL5 and anandamide (AEA) levels as compared to CTL. GBS induced a massive weight and fat mass loss, improved insulin sensitivity and lipid profile, decreased C-reactive protein, leptin, and CCL2 levels. In SAT, increased expression of resistin, CCL2, CCL5 and tumour necrosis factor and reduced MGLL were shown in morbid obese patients pre-GBS when compared to CTL. GBS increased all endocannabinoids and reduced adipocytokines and CC chemokines. In morbid obese SAT, inverse correlations independent of body mass index were shown between palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) levels and inflammatory molecules. In vitro, OEA inhibited CCL2 secretion from adipocytes via ERK1/2 activation. In conclusion, GBS was associated with relevant clinical, metabolic and inflammatory improvements, increasing endocannabinoid levels in SAT. OEA directly reduced CCL2 secretion via ERK1/2 activation in adipocytes.

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Human-Specific Function of IL-10 in Adipose Tissue Linked to Insulin Resistance

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00341 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4552-4562 ◽

Cited By ~ 2

Author(s):

Juan R Acosta ◽

Beatriz Tavira ◽

Iyadh Douagi ◽

Agné Kulyté ◽

Peter Arner ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Mass Index ◽

Flow Cytometry ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Body Mass ◽

Model Assessment ◽

Fat Cell ◽

Anti Inflammatory

Abstract Objective Although IL-10 is generally considered as an anti-inflammatory cytokine, it was recently shown to have detrimental effects on insulin sensitivity and fat cell metabolism in rodents. Whether this also pertains to human white adipose tissue (hWAT) is unclear. We therefore determined the main cellular source and effects of IL-10 on human adipocytes and hWAT-resident immune cells and its link to insulin resistance. Methods Associations between hWAT IL-10 production and metabolic parameters were investigated in 216 participants with large interindividual variations in body mass index and insulin sensitivity. Adipose cells expressing or secreting IL-10 and the cognate IL-10 receptor α (IL10RA) were identified by flow cytometry sorting. Effects on adipogenesis, lipolysis, and inflammatory/metabolic gene expression were measured in two human primary adipocyte models. Secretion of inflammatory cytokines was investigated in cultures of IL-10–treated hWAT macrophages and leukocytes by Luminex analysis (Luminex Corp.). Results IL-10 gene expression and protein secretion in hWAT correlated positively with body mass index (BMI) and homeostasis model assessment-insulin resistance (HOMA-IR). Gene expression analyses in mature fat cells and flow cytometry–sorted hWAT-resident adipocyte progenitors, macrophages, and leukocytes demonstrated that the expression of IL-10 and the IL10RA were significantly enriched in proinflammatory M1 macrophages. In contrast to murine data, functional studies showed that recombinant IL-10 had no effect on adipocyte phenotype. In hWAT-derived macrophages and leukocytes, it induced an anti-inflammatory profile. Conclusion In hWAT, IL-10 is upregulated in proinflammatory macrophages of obese and insulin-resistant persons. However, in contrast to findings in mice, IL-10 does not directly affect human adipocyte function.

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Insulin Resistance, Body Mass Index and Coronary Atherosclerotic Stenosis in Obese Adults

10.21203/rs.3.rs-28915/v1 ◽

2020 ◽

Author(s):

Nianrong Zhang ◽

Yumeng Liu ◽

Guoshan Yang ◽

Biao Zhou ◽

Guanming Qi ◽

...

Keyword(s):

Insulin Resistance ◽

Body Mass Index ◽

Body Mass ◽

Metabolic Surgery ◽

Coronary Stenosis ◽

Model Assessment ◽

Obese Patients ◽

Clinical Indicators ◽

Atherosclerotic Stenosis ◽

Significant Difference

Abstract Background: Obesity is associated with an increased risk of all-cause mortality. Mortality related to excess body weight occurs mostly due to coronary artery disease(CAD). This study is to observe the prevalence of coronary atherosclerotic stenosis in obese young-middle adults and outcomes of coronary stenosis in patients with obesity after metabolic surgery. Methods: Patients with obesity undergoing metabolic surgery were included from December 2015 to June 2017.Coronary computed tomography angiography(CTA) was examined preoperatively. Patients were divided into the stenosis group and the non-stenosis group and differences in clinical indicators and Homeostasis model assessment insulin resistance(HOMA-IR)were compared between the two groups. After metabolic surgery, the clinical indicators and severity of coronary stenosis were compared with those before metabolic surgery. Results: Among 217 consecutive obese patients with a mean body mass index(BMI) of 37.92±6.14kg/m2, 58(26.72%) patients were diagnosed with coronary atherosclerotic stenosis. Compared with the non-stenosis group, patients in the stenosis group had a more elder age, higher rates of male, smoking, hypertension and type 2 diabetes mellitus(T2DM), and higher levels of glycated haemoglobin(HbA1C),fasting blood glucose(FBG),fasting C-peptide and HOMA-IR(P<0.05). While there was no significant difference in BMI, waist circumstance(WC), serum lipid levels (P＞0.05). The multivariate binomial logistic regression analysis showed that the age(β=0.070, OR=1.073, 95% CI 1.028-1.120, P<0.001),smoking(β=1.371, OR=3.941, 95% CI 1.257-12.357, P=0.019), and HOMA-IR(β=0.040, OR=1.041, 95% CI 1.000-1.083, P=0.047) were independent risk factors of coronary stenosis. After metabolic surgery, coronary stenosis relieved in 11/19 cases (57.89%), in which 9 cases got complete remission; coronary stenosis was aggravated in one case and remained the same in another one case.Conclusions: HOMA-IR, as well as age and smoking, is an independent risk factor for CAD in obese patients. Metabolic surgery is possibly helpful to reverse mild to moderate coronary atherosclerotic stenosis in patients with obesity.

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Chemotactic cytokines, obesity and type 2 diabetes:in vivoandin vitroevidence for a possible causal correlation?

Proceedings of The Nutrition Society ◽

10.1017/s0029665109990218 ◽

2009 ◽

Vol 68 (4) ◽

pp. 378-384 ◽

Cited By ~ 41

Author(s):

Henrike Sell ◽

Jürgen Eckel

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Obese Patients ◽

Tissue Mass ◽

Tissue Biology ◽

Wide Range ◽

Adipose Tissue Mass

A strong causal link between increased adipose tissue mass and insulin resistance in tissues such as liver and skeletal muscle exists in obesity-related disorders such as type 2 diabetes. Increased adipose tissue mass in obese patients and patients with diabetes is associated with altered secretion of adipokines, which also includes chemotactic proteins. Adipose tissue releases a wide range of chemotactic proteins including many chemokines and chemerin, which are interesting targets for adipose tissue biology and for biomedical research in obesity and obesity-related diseases. This class of adipokines may be directly linked to a chronic state of low-grade inflammation and macrophage infiltration in adipose tissue, a concept intensively studied in adipose tissue biology in recent years. The inflammatory state of adipose tissue in obese patients may be the most important factor linking increased adipose tissue mass to insulin resistance. Furthermore, chemoattractant adipokines may play an important role in this situation, as many of these proteins possess biological activity beyond the recruitment of immune cells including effects on adipogenesis and glucose homeostasis in insulin-sensitive tissues. The present review provides a summary of experimental evidence of the role of adipose tissue-derived chemotactic cytokines and their function in insulin resistancein vivoandin vitro.

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Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2373 ◽

2013 ◽

Vol 98 (12) ◽

pp. 4899-4907 ◽

Cited By ~ 235

Author(s):

Kyung Hee Park ◽

Lesya Zaichenko ◽

Mary Brinkoetter ◽

Bindiya Thakkar ◽

Ayse Sahin-Efe ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Mass Index ◽

Body Mass ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Cvd Risk ◽

Baseline Serum ◽

The Metabolic Syndrome ◽

Increased Risk

Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = −0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66–33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72–19.60), high triglycerides (OR = 3.89, 95% CI = 1.16–13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18–9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

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Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

Genes ◽

10.3390/genes9080410 ◽

2018 ◽

Vol 9 (8) ◽

pp. 410 ◽

Cited By ~ 7

Author(s):

Daniel Castellano-Castillo ◽

Isabel Moreno-Indias ◽

Jose Carlos Fernandez-Garcia ◽

Mercedes Clemente-Postigo ◽

Manuel Castro-Cabezas ◽

...

Keyword(s):

Insulin Resistance ◽

Dna Methylation ◽

Adipose Tissue ◽

Messenger Rna ◽

Density Lipoprotein ◽

Complement Factor ◽

Mrna Levels ◽

Model Assessment ◽

Tissue Samples ◽

Obese Class

Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns out to be an important protein in metabolic disorders, via either inflammation or the C3 subproduct acylation stimulating protein (ASP) which directly stimulates lipid storage. In this study, we analyze C3 DNA methylation in adipose tissue from subjects with a different grade of obesity. Adipose tissue samples were collected from subjects with a different degree of obesity determined by their body mass index (BMI) as: Overweight subjects (BMI ≥ 25 and <30), obese class 1/2 subjects (BMI ≥ 30 and <40) and obese class 3 subjects (BMI ≥ 40). C3 DNA methylation was measured for 7 CpGs by pyrosequencition using the Pyromark technology (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre-designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was measured using a ELISA kit. The data were analyzed using the statistic package SPSS. C3 DNA methylation levels were lower in the morbid obese group. Accordingly, C3 methylation correlated negatively with BMI and leptin. However, C3 mRNA levels were more associated with insulin resistance, and positive correlations with insulin, glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity variables, such as BMI and leptin, while the C3 mRNA levels were associated to glucose metabolism.

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