Inflammation biomarkers and inflammatory genes expression in metabolically healthy obese patients

Background and aimsObesity without metabolic alterations (Metabolically Healthy Obesity, MHO) is a condition with a risk of death and cardiovascular disease lower than that of obesity associated with metabolic alterations (Metabolically Unhealthy Obesity, MUO) and similar to that of healthy non obese individuals. Inflammation is considered as a key risk factor mediating the adverse health outcomes in obesity.Methods and resultsWe compared circulating levels of thirteen major cytokines and adipokines and the expression profiles of fifteen pro-inflammatory and two anti-inflammatory genes in visceral and subcutaneous adipose tissue in a series of 16 MHO patients and in 32 MUO patients that underwent bariatric surgery. MHO was defined according to the most applied definition in current literature.Serum levels of a large set of major cytokines and adipokines did not differ between MHO and MUO patients (p ≥ 0.15). Analyses of the expression profile of pro-inflammatory and anti-inflammatory genes in subcutaneous and visceral adipose tissue failed to show differences between MHO and MUO patients (p ≥ 0.07). Sensitivity analyses applying two additional definitions of MHO confirmed the results of the primary analysis.ConclusionIn a series of metabolically healthy obese patients neither circulating levels of major cytokines and adipokines nor the gene expression profile of a large set of pro-inflammatory and anti-inflammatory genes in subcutaneous and visceral fat differed from those in metabolically unhealthy obese patients.     

The relationship of visfatin/pre-B-cell colony-enhancing factor/nicotinamide phosphoribosyltransferase in adipose tissue with inflammation, insulin resistance, and plasma lipids

Visfatin/pre-B-cell colony-enhancing factor (PBEF)/nicotinamide phosphoribosyltransferase (Nampt) has been proposed as an insulin-mimicking adipocytokine predominantly secreted from visceral adipose tissue (VAT) and correlated with obesity. However, recent evidence challenged this proposal and instead suggested visfatin/PBEF/Nampt as a proinflammatory cytokine. The study aimed to examine whether visfatin/PBEF/Nampt was predominantly expressed in VAT and was correlated with obesity. The relationship of visfatin/PBEF/Nampt gene expression in adipose tissues with proinflammatory gene expression and metabolic phenotypes was also examined. The relative messenger RNA (mRNA) levels of visfatin/PBEF/Nampt, macrophage-specific marker CD68, and proinflammatory genes were measured in paired abdominal VAT and subcutaneous adipose tissues (SAT) and from 53 nondiabetic adults using quantitative real-time polymerase chain reaction. Fasting glucose, insulin, triglyceride, cholesterol, and uric acid levels were measured; and systemic insulin sensitivity was quantified with modified insulin suppression tests. There was no difference in visfatin/PBEF/Nampt mRNA levels between VAT and SAT, and neither was associated with measures of obesity. Visfatin/PBEF/Nampt mRNA levels were strongly correlated with proinflammatory gene expression including CD68 and tumor necrosis factor-α gene in both VAT and SAT. The VAT and SAT visfatin/PBEF/Nampt mRNA expressions were positively correlated with steady-state plasma glucose concentrations measured with modified insulin suppression tests, a direct measurement of systemic insulin resistance (r = 0.42, P = .03 and r = 0.44, P = .03, respectively). The VAT visfatin/PBEF/Nampt mRNA expression was also positively correlated with fasting triglyceride (r = 0.42, P = .002) and total cholesterol levels (r = 0.37, P = .009). Visfatin/PBEF/Nampt is not predominantly secreted from VAT and is not correlated with obesity. Our findings suggest that visfatin/PBEF/Nampt is a proinflammatory marker of adipose tissue associated with systemic insulin resistance and hyperlipidemia.     

Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans

CONTEXT: Visfatin was recently identified as a protein highly expressed and secreted in adipose tissue with insulin-mimetic effect and is a candidate hormone to help explain the association among adipose tissue expansion, insulin resistance, and type 2 diabetes. OBJECTIVE: The objective of the study was to assess expression of visfatin in lean and obese subjects and in sc and visceral adipose tissue and moreover to explore the role of visfatin on insulin resistance in humans. DESIGN: We measured circulating visfatin and its mRNA expression in sc adipose tissue (SAT) in lean and obese subjects. Furthermore, we measured visfatin mRNA in visceral adipose (VAT) and SAT by quantitative RT-PCR. Finally, plasma visfatin and its mRNA in SAT were measured under free fatty acid-induced insulin resistance in healthy subjects. RESULTS: Plasma visfatin and its mRNA in SAT were significantly lower in obese subjects, compared with normal-weight controls. Both circulating visfatin and SAT visfatin mRNA were negatively correlated with body mass index, whereas no correlation was found with homeostasis model assessment. Significantly higher visfatin mRNA was found in VAT of obese subjects, compared with lean controls. Interestingly, visfatin mRNA in VAT was positively correlated with BMI. Elevation of free fatty acid induced a condition of insulin resistance but did not affect either circulating visfatin or its mRNA. CONCLUSIONS: Our findings show that, in human obesity, plasma visfatin is reduced, whereas visfatin mRNA is differentially regulated in SAT and VAT. Visfatin is not related to insulin resistance either as assessed by homeostasis model assessment or during lipid infusion.     

Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

OBJECTIVE: To investigate whether adiponectin receptor genes (AdipoR1 and AdipoR2) expression in human subcutaneous (SAT) and visceral (VAT) adipose tissue in severely obese patients with or without diabetes is related to adiponectin gene (APM1) expression and in vivo metabolic parameters. DESIGN: Cross-sectional, clinical research study. SUBJECTS: Total RNA was extracted from SAT and VAT tissue obtained during surgery from 13 lean controls, 30 obese diabetic patients, 19 obese glucose-intolerant patients and 54 obese subjects with normal glucose tolerance. MEASUREMENTS: Tissue expression of APM1, AdipoR1 and AdipoR2, tissue concentration of adiponectin (ApN), and metabolic variables. RESULTS: APM1 expression was higher in SAT than VAT (1.06+/-0.76 vs 0.69+/-0.52, P<0.0001) as was AdipoR1 (1.17+/-0.70 vs 0.66+/-0.38, P<0.0001) and AdipoR2 (7.02+/-6.19 vs 0.75+/-0.64, P<0.0001). In SAT, APM1 and AdipoR1 expression tended to be lower - by 0.38+/-0.22 and 0.35+/-0.22, respectively - and AdipoR2 expression was markedly depressed - by 4.82+/-1.93 - in association with obesity, whereas presence of diabetes had no additional effect. In VAT, APM1 and AdipoR1 expressions were also reduced - by 0.36+/-0.16 and 0.30+/-0.11, respectively - in association with obesity. Within both SAT and VAT, expression levels of APM1, AdipoR1 and AdipoR2 were all positively interrelated. Tissue ApN concentrations in SAT were similar across groups, whereas ApN levels in VAT were substantially lower in association with obesity (by an average of 63+/-12 ng/mg total protein, P<0.0001). In multivariate models adjusting for sex, age and obesity, serum triglyceride concentrations were reciprocally related to APM1 (r=-0.27, P<0.02), AdipoR1 (r=-0.37, P<0.002 and AdipoR2 expression (r=-0.37, P<0.002) in VAT. Likewise, plasma insulin concentrations were inversely related only to APM1 in VAT (r=-0.25, P<0.03). CONCLUSIONS: Severe obesity is associated with suppressed expression of both ApN and its receptors in both SAT and VAT, the expression levels in VAT are specifically linked with hyperinsulinemia and dyslipidemia.     

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

BACKGROUND: Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. METHODS: We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. RESULTS: Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. CONCLUSIONS: The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are independent of amounts of VAT or SAT.     

Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines

Objective The controversial results on the physiopathological role of visfatin led us to examine both circulating visfatin levels and gene expression in visceral (VAT) and subcutaneous fat (SAT) in a homogeneous group of morbidly obese women. Design, patients and measurements We analysed circulating levels of several adipo/cytokines in 133 Spanish women: 40 lean (C) [body mass index (BMI) < 25 kg/m²] and 93 morbidly obese (MO) (BMI > 40 kg/m²). In the MO group, we found 31 diabetic and 62 nondiabetic subjects. We obtained follow‐up blood samples at 6 and 12 months after bariatric surgery from 30 MO patients. We determined the circulating levels of visfatin, adiponectin, interleukin‐6 (IL6), C‐reactive protein (CRP), resistin and tumour necrosis factor‐α (TNFα) by ELISA, and visfatin, adiponectin, IL6, resistin and TNFα gene expression in SAT and VAT by real‐time RT‐PCR. Results Circulating visfatin levels were higher in MO women compared with lean controls (C = 1·43 ± 0·14 μg/l, MO = 3·60 ± 0·29 μg/l, P < 0·001). After bariatric surgery‐induced weight loss, visfatin levels were reduced significantly over 12 months. Visfatin expression in SAT and VAT was similar, but significantly higher in MO compared to C and independent of the presence of diabetes mellitus. Circulating visfatin levels were positively related to IL6 and CRP levels. Visfatin gene expression in VAT and SAT was strongly related to IL6 and TNFα expression. Conclusion In a homogeneous cohort of morbidly obese women, our findings show that visfatin has a strong relationship with pro‐inflammatory factors in severe obesity.     

Relationship between vaspin gene expression and abdominal fat distribution of Korean women

Visceral adipose tissue-derived serpin (vaspin) is a novel adipokine that is thought to have insulin-sensitizing effects. We investigated vaspin mRNA expression in abdominal adipose tissue and examined how gene expression related to abdominal fat distribution and metabolic parameters in Korean women. We measured anthropometric variables, metabolic parameters, serum vaspin concentration, and vaspin mRNA expression in abdominal adipose tissue obtained from women who underwent abdominal gynecological surgery and were aged 18-67 years (n = 85). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area were measured in 40 subjects using computed tomography (CT). Vaspin expression was analyzed by real-time quantitative RT-PCR according to abdominal fat distribution. Vaspin mRNA expression was greater in adipocytes than in stroma/vascular cells. In the total subjects, vaspin expression was significantly higher in SAT than in VAT. Vaspin expression in SAT in subcutaneous fat type (VSR ≤ 0.3) was significantly higher than in visceral fat type (VSR > 0.3), although vaspin expression in VAT was similar between subcutaneous and visceral fat type. There was a significant negative correlation between vaspin expression in SAT and VAT area (r = -0.55, p = 0.001). Serum vaspin concentration was significantly correlated with fasting insulin (r = 0.30, p = 0.02), HOMA-IR (r = 0.29, p = 0.02), and the ratio of vaspin expression in VAT to vaspin expression in SAT (r = 0.41, p = 0.04). Vaspin expression in abdominal adipose tissue was adipocyte-specific and vaspin expression in SAT decreased as VAT area increased.     

The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue

Objective:Hypoadiponectinemia observed in obesity is associated with insulin resistance, diabetes and atherosclerosis. The aim of the present study was to investigate secretion of adiponectin and its multimeric isoforms by explants derived from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese and non-obese subjects.Design:Paired samples of SAT and VAT and blood samples were obtained from 23 subjects (10 non-obese and 13 obese) undergoing elective abdominal surgery. Total adiponectin quantities and adiponectin isoforms were measured in conditioned media of explants derived from SAT and VAT using enzyme-linked immunosorbent assay and non-denaturing western blot, respectively.Results:Total adiponectin plasma levels were lower in obese than in non-obese subjects (P<0.05). Secretion of total adiponectin in adipose tissue (AT) explants was lower in obese than in non-obese subjects in SAT (P<0.05) but not in VAT. In both, SAT and VAT, the most abundant isoform released into conditioned media was the high-molecular weight (HMW) form. Its relative proportion in relation to total adiponectin was higher in conditioned media of explants from both fat depots when compared with plasma (P<0.001). The proportion of secreted HMW vs total adiponectin was higher in VAT than in SAT explants in the group of non-obese individuals (49.3±3.1% in VAT vs 40.6±2.8% in SAT; P<0.01), whereas no difference between the two depots was found in obese subjects (46.2±3.0 % in VAT vs 46.0±2.4 % in SAT).Conclusion:Obesity is associated with the decrease of total adiponectin secretion in SAT. The profile of adiponectin isoforms secreted by SAT and VAT explants differs from that in plasma. Secretion of total adiponectin and HMW isoform of adiponectin are different in obese and non-obese subjects in relation to AT depot.     

Association between low SIRT1 expression in visceral and subcutaneous adipose tissues and metabolic abnormalities in women with obesity and type 2 diabetes

Aims

To assess the importance of adipose tissue sirtuin 1 (SIRT1) in the regulation of whole-body metabolism in humans with obesity and type 2 diabetes.

Methods

In total, 19 non-diabetic obese women, 19 type 2 diabetic women undergoing gastric bypass surgery, and 27 normal-weight women undergoing gynecological surgery (total 65 women) were enrolled. Their anthropometric variables, abdominal fat distribution and metabolic parameters, serum adiponectin concentrations, and SIRT1 mRNA and protein and adiponectin mRNA expressions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured.

Results

SIRT1 mRNA levels in VAT and SAT were similar and these levels were suppressed in obese and type 2 diabetic women compared to normal-weight subjects. These decreases in SIRT1 expression were observed in both adipocytes and non-fat cells. There was a strong association between adipose tissue SIRT1 mRNA and protein levels. Adipose SIRT1 expression correlated inversely with HOMA-IR and other insulin resistance-related parameters. Adipose SIRT1 and adiponectin mRNA expression correlated very strongly and positively. SIRT1 mRNA level in VAT correlated inversely with visceral obesity whereas its expression in SAT correlated negatively with body mass index.

Conclusions

Adipose tissue SIRT1 may play a key role in the regulation of whole body metabolic homeostasis in humans. Downregulation of SIRT1 in VAT may contribute to the metabolic abnormalities that are associated with visceral obesity.     

Relation of visceral adiposity to circulating natriuretic peptides in ambulatory individuals

Natriuretic peptides have important roles in the regulation of vasomotor tone, salt homeostasis, and ventricular remodeling. Lower natriuretic peptide levels observed in obese individuals may underlie the greater cardiovascular risk associated with obesity. Thus the aim of this study was to determine whether lower natriuretic peptide levels in obesity are attributable to differences in regional fat distribution. We investigated the relation of plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to regional adiposity in 1,873 community-based individuals (46% women, mean age 45 years). Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured by multidetector computed tomography. In gender-specific multivariable analyses adjusting for age and blood pressure, log NT-pro-BNP was inversely associated with VAT in men (beta -0.11 per standard deviation increment, p <0.001) and women (beta -0.19, p <0.001). Log NT-pro-BNP was inversely associated with SAT in women only (beta -0.14, p <0.001). In models containing VAT and SAT, only VAT was significantly associated with log NT-pro-BNP (men, beta -0.137, p <0.001; women, beta -0.184, p <0.001). VAT remained associated with log NT-pro-BNP even after adjustment for body mass index and waist circumference (beta -0.119, p <0.001) and in analyses restricted to nonobese patients (beta -0.165, p <0.001). Adjustment for insulin resistance attenuated the associations of NT-pro-BNP with VAT and SAT. In conclusion, this study demonstrates that circulating NT-pro-BNP is related to variations in regional and particularly visceral adiposity. These findings suggest that excess visceral adiposity and concomitant hyperinsulinemia may contribute to the natriuretic peptide "deficiency" observed in obesity.     

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors α and β were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-α, CD68, IL-6, IL-8, ERα, ERβ) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.     

The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects

Obesity is a well-known chronic low-grade inflammation condition characterized by dysregulated adipokine secretion and function. Both CTRP12 and CTRP13 are adipokines that influence glucose and lipid metabolism. We aimed to investigate CTRP12, CTRP13, and inflammatory gene expressions in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery in comparison with the normal weight women. This case-control study included 20 obese [body mass index (BMI) > 35–40 kg/m²] candidates for bariatric surgery and 20 normal-weight women (BMI <25 kg/m²) as control group, who underwent elective surgeries. Real-time PCR was used to evaluate mRNA expression levels of CTRP12, CTRP13, and inflammatory genes in SAT and VAT from both groups. We observed significantly higher mRNA expression of CTRP12 in SAT (p = 0.048) and VAT (p = 0.046) from obese patients compared to the controls. There was significantly greater expression of IL-6 and MCP-1 inflammatory genes in SAT (p = 0.013 and p = 0.005 respectively) and VAT (p = 0.000 and p = 0.001 respectively) of obese patients compared to the control group. IL-1β (p = 0.015) and TNF-α (p = 0.014) expressions significantly increased in VAT from obese patients compared to the control group. Spearman correlation analysis showed that CTRP12 expression significantly correlated with obesity indices. Our findings showed that CTRP12 significantly increased in both VAT and SAT of obese group. More importantly, we observed a positive correlation between CTRP12 with inflammatory parameters. These results indicated that CTRP12 might be part of an intricate network for glucose metabolism and obesity-related inflammation processes.     

Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study

Visceral adipose tissue (VAT) is an independent risk factor for metabolic and cardiovascular disorders. There has been no study that demonstrated different abdominal fat distribution between Asian and Caucasian men. As the Japanese are less obese but more susceptible to metabolic disorders than Caucasians, they may have larger VAT than Caucasians at similar levels of obesity. We compared the abdominal fat distribution of the Japanese (n=239) and Caucasian-American (n=177) men aged 40-49 years in groups stratified by waist circumference in a population-based sample. We obtained computed tomography images and determined areas of VAT and subcutaneous adipose tissue (SAT). We calculated VAT to SAT ratio (VSR). The Japanese men had a larger VAT and VSR in each stratum, despite substantially less obesity overall. In multiethnic studies, difference in abdominal fat distribution should be considered in exploring factors related to obesity.     

Associations of Obesity With Lipoprotein Subfractions in Japanese American,African American,and Korean Men

BackgroundBoth indices of obesity and lipoprotein subfractions contribute to coronary heart disease risk. However, associations between indices of obesity and lipoprotein subfractions remain undetermined across different ethnic groups.ObjectiveThis study aims to examine the associations of indices of obesity in Japanese Americans, African Americans, and Koreans with lipoprotein subfractions.MethodsA population-based sample of 230 Japanese American, 91 African American, and 291 Korean men ages 40 to 49 was examined for indices of obesity—that is, visceral and subcutaneous adipose tissue (VAT and SAT, respectively); waist circumference; and body mass index—and for lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Multiple regression analyses were performed in each of the 3 ethnic groups to examine the associations of each index of obesity with lipoprotein.ConclusionsVAT had significant positive associations with total and small low-density lipoprotein (LDL) and a significant negative association with large high-density lipoprotein (HDL) in all 3 ethnicities (p < 0.01). SAT, waist circumference, and body mass index had significant positive associations with total and small LDL in only Japanese Americans and Koreans, whereas these indices had significant inverse associations with large HDL in all ethnic groups (p < 0.01). Compared with SAT, VAT had larger R² values in the associations with total and small LDL and large HDL in all 3 ethnic groups. VAT is significantly associated with total and small LDL and large HDL in all 3 ethnic groups. The associations of SAT, waist circumference, and body mass index with lipoprotein subfractions are weaker than the associations of VAT in all 3 ethnic groups.     

Association of Periaortic Fat and Abdominal Visceral Fat with Coronary Artery Atherosclerosis in Chinese Middle Aged and Elderly Patients Undergoing Computed Tomography Coronary Angiography

Background and Aims:Coronary artery disease (CAD) is usually caused by atherosclerosis, which is associated with general obesity and stronger associations with localized ectopic fat depots have been reported. We measured body ectopic fat distribution in Chinese patients to determine the association with coronary artery atherosclerosis (CA).Methods:Patients undergoing coronary computed tomography angiography (CCTA) who agreed to participate in the study (n = 750, 50.4% men, mean age 64.8 years) had cardiovascular disease and risk assessment. Body ectopic fat depots were measured from CT and their association with CA, determined from CCTA, was evaluated by univariate and multivariate logistic regression models.Results:CAD with CA (CAD-CA) was present in 57.2% of participants with CAD of moderate/severe CA (CAD-msCA) present in 23.5% and both were significantly more frequent in men than in women. Overall, men had greater body mass index (BMI) but there was no difference in waist circumference (WC) between genders. However, significantly higher visceral adipose tissue (VAT) and periaortic fat volume (PAFV) were observed in men, whereas women had significantly higher abdominal subcutaneous adipose tissue (SAT). With increasing age, there was a significant decline in BMI, WC and SAT in men, but a significant increase of WC and VAT, PAFV and epicardial fat volume (EFV) in women. A high proportion of non-calcified plaques was observed in CAD-CA, 55.3% in CAD of minimal/mild CA (CAD-mmCA) with 38.7% exclusively non-calcified plaques, and 59.7% in CAD-msCA with multiple type plaques containing non-calcified ones. Multivariate logistic regression showed a significant association of PAFV with CAD-CA and CAD-msCA that was independent of general obesity and clinical risk factors, and independent of abdominal obesity in the highest PAFV quartile patients. VATA was associated with an increased prevalence of CAD-msCA in the patients in the upper 2 VATA quartiles that was independent of clinical risk factors and both general and abdominal obesity.Conclusions:We found age and gender differences of body ectopic fat distribution in Chinese patients with higher VAT and PAFV in men and higher SAT in women. With increased age, there was a decline of WC and SAT in men but not in women and an increase in WC, VAT and PAFV in women but not in men. PAFV was significantly associated with overall CAD-CA and CAD-msCA, while VAT was associated with CAD-msCA.     

Altered pattern of cannabinoid type 1 receptor expression in adipose tissue of dysmetabolic and overweight patients

In overweight patients (OW), the increased peripheral activity of the endocannabinoid system in visceral adipose tissue (VAT) may be mediated by cannabinoid type 1 (CB1) receptor expression. We determined whether CB1 receptor splice variants and messenger RNA (mRNA) levels in perirenal and subcutaneous adipose tissues are associated with obesity and metabolic syndrome (MetS). Gene expression with multiple-primers real-time polymerase chain reaction (TaqMan; Applied Biosystem, Weiterstadt, Germany) was performed to study VAT and paired subcutaneous adipose tissue (SAT) mRNA from 36 consecutive patients undergoing nephrectomy. Cannabinoid type 1A and CB1E mRNAs variants with the longer version of exon 4 were expressed. The CB1 expression in perirenal VAT significantly correlated with body mass index (BMI). Paired subcutaneous/perirenal samples from normal-weight patients (BMI <25 kg/m²) showed higher CB1 expression in SAT (P = .002), whereas in OW (BMI ≥25 kg/m²), the higher CB1 expression was in VAT (P = .038). In unpaired samples, SAT of normal-weight patients had significantly higher CB1 mRNA levels compared with SAT of OW, whereas higher CB1 expression (P = .009) was found in VAT of OW (n = 25). Overweight patients with increased visceral CB1 expression had higher waist circumference (P < .01), insulin (P < .01), and homeostasis model assessment index (P < .01). In addition, patients with the MetS (n = 22) showed higher CB1 expression in perirenal adipose tissues (P = .007). Visceral adipose CB1 expression correlated with BMI. Overweight patients and those with MetS showed a CB1 expression pattern supporting a CB1-mediated overactivity of the endocannabinoid system in human VAT.     

Plasma cytokines, glomerular filtration rate and adipose tissue cytokines gene expression in chronic kidney disease (CKD) patients

Background and AimSystemic inflammation is a hallmark of chronic kidney disease (CKD) and obesity represents a major risk factor for CKD. We investigated the relationship between plasma interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) and the glomerular filtration rate (GFR) in 75 stage 2–5 CKD patients.Methods and ResultsWe studied the steady-state relationship between plasma and subcutaneous adipose tissue (SAT) gene expression of the same cytokines in 19 patients and in 17 well-matched healthy subjects (HS) and compared SAT gene expression of these cytokines and of two additional cytokines (IL-1β and IL-8) in CKD patients and in HS.Plasma IL-6 and TNF-α were higher in CKD patients than in HS (P < 0.001). IL-6 was similarly increased in patients with mild, moderate and severe CKD and largely independent of the GFR (r = ?0.03, P = NS). TNF-α was inversely related to GFR, which was the first factor in rank (β = ?0.37, P = 0.001) explaining the variability in TNF-α in CKD. SAT messenger RNA (mRNA) levels of IL-6, TNF-α, IL- β and IL-8 were similar in CKD patients and in HS. Plasma and SAT mRNA levels of IL-6 and TNF-α levels were largely unrelated.ConclusionsPlasma IL-6 rises early in CKD and does not show any further increase at more severe stages of CKD, whereas TNF-α is inversely associated with the GFR indicating a substantial difference in the dynamics of the relationship between these cytokines and renal function. Cytokines are not overexpressed in SAT in these patients, and circulating IL-6 and TNF-α are dissociated from the corresponding mRNA levels in SAT, both in CKD patients and in HS.     

Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in obese subjects

OBJECTIVE: The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor alpha (TNFalpha) and two glucocorticoid-regulated adipokines able to influence the metabolic control. DESIGN AND SUBJECTS: Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1+/-5.3 kg/m(2)). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9+/-5.1 kg/m(2)). MEASUREMENTS: Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFalpha and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11beta-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFalpha. Western blot analysis to evaluate 11beta-HSD1 protein expression. RESULTS: In the majority of the obese subjects, VAT expresses more 11beta-HSD1 than SAT. VAT 11beta-HSD1 expression was not associated with metabolic disorders. SAT 11beta-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11beta-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11beta-HSD1 was associated with increased adiponectin and TNFalpha expression and decreased serum adiponectin levels (all P's <0.05). CONCLUSIONS: In obese subjects, increased 11beta-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release.