Cecilia Invitti

Metabolic syndrome in obese Caucasian children : prevalence using WHO-derived criteria and association with nontraditional cardiovascular risk factors

Objective:Studies on the prevalence of metabolic syndrome (MS) in European obese children using child-based criteria are scanty. Moreover, it is unknown if nontraditional cardiovascular disease (CVD) risk factors are associated with the MS at this early age in these subjects.Design and subjects:We studied the prevalence of the MS in 588 Caucasian obese children and adolescents by devising a World Health Organization derived definition and child-specific criteria, whose deviation from normalcy was based on an age, sex, and ethnically comparable control group of 1363 subjects. In a subgroup of 206 obese children, we investigated the association of the MS with nontraditional CVD risk factors.Measurements:Fasting blood samples for glucose and lipids measurements were taken in both control and obese children. In addition, the obese children underwent an oral glucose tolerance test. In the subgroup of 206 obese children, albumin excretion rate , plasma uric acid, fibrinogen, plasminogen activator inhibitor type 1(PAI-1), C-reactive protein, interleukin 6 and white blood cells were also measured.Results:The prevalence of MS was 23.3%. A similar prevalence of 23% of MS was recorded in the subgroup of 206 obese children in whom measurements of nontraditional CVD risk factors were available. After adjustment for the degree of obesity, subjects with MS had significantly higher uric acid (6.6±0.23 vs 6.1±0.12 mg/dl, P<0.0001) and PAI-1 plasma concentrations (231.4±25.50 vs 214.3±12.96 ng/ml, P<0.05) and a higher frequency of microalbuminuria (37 vs 20%, P<0.05) than those without MS. Microalbuminuria, uric acid and PAI-1 explained 10.6% of the variance of MS.Conclusion:Approximately, a quarter of Caucasian obese children have the MS. The association of MS with several nontraditional risk factors for CVD early in life suggests a heightened CVD risk in these individuals.

Type 2 diabetes and metabolic syndrome are associated with increased expression of 11β-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, 11β-hydroxysteroid dehydrogenase type 1 (11β-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 α (TNFα) 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/m2). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9±5.1 kg/m2).Measurements:Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFα and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFα. Western blot analysis to evaluate 11β-HSD1 protein expression.Results:In the majority of the obese subjects, VAT expresses more 11β-HSD1 than SAT. VAT 11β-HSD1 expression was not associated with metabolic disorders. SAT 11β-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 11β-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11β-HSD1 was associated with increased adiponectin and TNFα expression and decreased serum adiponectin levels (all P’s <0.05).Conclusions:In obese subjects, increased 11β-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.

Protein Kinase A Regulatory Subunits in Human Adipose Tissue Decreased R2B Expression and Activity in Adipocytes From Obese Subjects

OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity.

Predictors of the early impairment of renal disease in human obesity

Objective:The mechanisms underlying the association of the increased albumin excretion rate (AER) with adiposity have yet to be clarified. We therefore investigated (1) the predictors of AER after 3 months of lifestyle intervention in a large cohort of nondiabetic obese women and (2) the relationships between AER and the adipose tissue gene expression of adipokines linked to inflammation and insulin resistance.Subjects:A total of 269 obese nondiabetic women (age 49.9±13.1 years, body mass index (BMI) 36.8±4.6 kg m−2) participated in this program. Measurements used were anthropometrics parameters, blood pressure, oral glucose tolerance test, lipids, creatinine, AER, homeostasis model assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3 (SOCS-3), tumor necrosis factor α (TNF-α), pentraxine 3 (PTX-3), angiotensinogen and angiotensin-converting enzyme, and a blood sample was also taken from this group for the measurement of circulating adiponectin, interleukin-6, TNF-α and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio ⩾3.5 mg mmol−1. Real-time PCR was used to quantify mRNA.Results:Six percent of obese women had microalbuminuria. When dividing the whole cohort into three groups according to AER changes (decrease, stability and increase), we noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for all) only in women who had a decrease in AER, whereas BMI and waist circumference significantly decreased in all the three groups (P<0.05). At baseline, higher AER was associated to significantly higher adipose tissue mRNA expression levels of SOCS-3 and PTX-3 (P<0.05) and to higher TNF-α and angiotensinogen expression.Conclusions:In obese women, weight loss alone is not sufficient to induce the AER decrease that occurs only with a concomitant improvement in glucose homeostasis. The adipose tissue gene expression profile seems to favor the early renal impairment often seen in obese subjects.