Monica D’Adamo

Relationship between plasma free fatty acids and uncoupling protein‐3 gene expression in skeletal muscle of obese subjects: in vitro evidence of a causal link

objective To investigate whether skeletal muscle uncoupling protein‐2 (UCP2) and uncoupling protein‐3 (UCP3) gene expression is altered in massive obesity and whether it correlates with in vivo insulin sensitivity and with metabolic and hormonal status.

Effects of whole body vibration plus diet on insulin-resistance in middle-aged obese subjects.

We investigated the early effects of whole body vibration (WBV) added to hypocaloric diet on insulin-resistance and other parameters associated with glucose regulation in sedentary obese individuals. We randomly assigned 34 patients to WBV plus hypocaloric diet (WBV group) or diet alone (CON group) for 8 weeks. Fasting and post-load glucose, insulin, lipids, C-reactive protein, tumor necrosis factor-α, leptin, adiponectin were assessed. Insulin sensitivity index (ISI) was derived from oral-glucose-tolerance test. Body composition was evaluated with dual-energy X-ray absorptiometry. Both groups lost approximately 5% of weight, with greater reduction of body fat in WBV than in CON (-7.1±1.2 Kg vs. -5.3±1.0 Kg, p=0.003). Percent variation of ISI was more pronounced in WBV than in CON group (+35±4% vs. + 22±5%, p=0.002), accompanied by slight improvement in post-load glucose (-1.07±0.02 vs. - 0.12±0.01 mmol/l, p=0.031) but without changes in fasting levels. Adiponectin significantly increased in WBV group compared with CON (p=0.021 for comparison) whereas no differences in leptin and inflammatory markers were observed. In middle-aged sedentary obese subjects, WBV added to hypocaloric diet for 8 weeks improved body composition, insulin-resistance, glucose regulation and adiponectin levels to a greater extent compared with diet alone. Efficacy and feasibility of this approach in the long term need to be ascertained.

Magnetic Resonance Imaging Determined Visceral Fat Reduction Associates with Enhanced IL-10 Plasma Levels in Calorie Restricted Obese Subjects

Background Obesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI) protocol before and after weight loss. Materials and Methods In 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight. Results Weight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05), increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03), and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively). A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05) and IL-6 (r = 0.19 p<0.05) plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels. Conclusion The reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.

MicroRNA 21 is up-regulated in adipose tissue of obese diabetic subjects

We investigated miR21 expression in omental (OAT) and subcutaneous adipose tissue (SAT) from 16 obese subjects undergoing bariatric surgery. Patients were divided into two age- and BMI-matched groups according to the presence of type 2 diabetes (T2D). miR21 was not differently expressed in OAT and SAT. However, miR21 expression was two folds greater in adipose tissue in patients with T2D. Accordingly, in primary cultures of adipocytes from non diabetic overweight subjects, miR21 expression increased after 24-h exposure to high glucose and insulin. In conclusion, miR21 appears linked to insulin-resistance deterioration within its pathophysiologic progression from obesity to T2D.

Relationship between Regional Fat Distribution and Hypertrophic Cardiomyopathy Phenotype

Background Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is characterized by heterogeneous phenotypic expression. Body mass index has been associated with LV mass and heart failure symptoms in HCM. The aim of our study was to investigate whether regional (trunk, appendicular, epicardial) fat distribution and extent could be related to hypertrophy severity and pattern in HCM. Methods Cardiovascular magnetic resonance was performed in 32 subjects with echocardiography-based diagnosis of HCM (22M/10F, 57.2±12.6 years) characterized by predominant hypertrophy at the interventricular septum (IVS). Regional fat distribution was assessed by dual-energy X-ray absorptiometry. Results Gender differences were detected in maximum IVS thickness (M: 18.3±3.8 mm vs. F: 14.3±4 mm, p = 0.012), right ventricle (RV) systolic function (M: 61.3±6.7%; F: 67.5±6.3%, p = 0.048), indexed RV end-diastolic (M: 64.8±16.3 ml/m2; F: 50.7±15.5 ml/m2, p = 0.04) and end-systolic volumes (M: 24.3±8.3 ml/m2; F: 16.7±7.4 ml/m2, p = 0.04). After adjusting for age and gender, maximum IVS thickness was associated with truncal fat (Tr-FAT) (β = 0.43, p = 0.02), but not with either appendicular or epicardial fat. Epicardial fat resulted independently associated with NT-proBNP levels (β = 0.63, p = 0.04). Late Gadolinium Enhancement-positive subjects displayed greater maximum IVS thickness (p = 0.02), LV mass index (p = 0.015) and NT-proBNP levels (p = 0.04), but no associations with fat amount or distribution were observed. Conclusion Truncal, but not appendicular or epicardial fat amount, seems to be related with maximum IVS thickness, the hallmark feature in our cohort of HCM patients. Further prospective researches are needed to assess a potential causative effect of central adiposity on HCM phenotype.

Insulin Resistance Affects Gene Expression in Endothelium

To the editor: We and others have found that either genetic insulin resistance or hyperinsulinemia may dampen insulin ability to activate the PI3-kinase/Akt pathway, leading to perturbation of endothelial nitric oxide synthase (eNOS) activation.1,2 However, little is known about insulin effects on transcription of antiatherogenic and proatherogenic genes in insulin resistant conditions. Therefore, we used a genetic model of vascular insulin resistance, primary human umbilical vein endothelial cells (HUVECs) naturally carrying the G972R Insulin Receptor Substrate-1 (IRS-1) variant,2 to investigate the effect of both genetic insulin resistance and hyperinsulinemia on transcription of atherosclerosis related genes. G972R IRS-1 variant reduces IRS-1 activation of the PI3-K/Akt pathway,3 and it has been associated to coronary artery disease and obesity.3,4 HUVECs carrying the wild-type (WT) or G972R IRS-1 variant were obtained as previously described.3 For the experiments, 3rd through 5th passage HUVEC-WT and 972 were incubated in serum free EGM-2 medium for 16 hours in the presence or absence of insulin 5×10−7 mol/L, to obtain a full effect of insulin on nitric oxide production.5 Total RNA was extracted from the HUVECs with Trizol reagent according to the manufacturer’s protocol. To profile gene expression pattern we made use of U133A Affymetrix DNA microarray containing a total number of 22283 probe sets corresponding to about 15 000 genes, using previously described methods.6 Gene expression profiling was obtained by …

A rare cardiac finding in a morbidly obese patient with severe hypertension

Dr. Fiore, Dr. Marinoni: A 46-year-old morbidly obese man was admitted to our emergency department (ED) with the acute onset of epigastric pain, nausea, and vomiting. He reported having a 10-year history of hypertension treated with doxazosin, atenolol, ramipril, and potassium canrenoate; in addition, during the last 2 years, he was treated with overnight continuous positive airway pressure (C-PAP) device for obstructive sleep apnea syndrome. He had never smoked or used illicit drugs. On examination, he appeared anxious. The height was 190 cm, the weight 155 kg, and the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) 42.9. The abdomen was soft and obese, with mild-to-moderate tenderness in the epigastrium, with no rebound tenderness or guarding. The bowel sounds were normal. The lungs were clear to auscultation, and the first and second heart sounds were faint but normal; a diastolic murmur (grade 1/6) was heard at the right sternal border. The temperature was 36.1 C, heart rate 97 beats per minute, blood pressure was 210/115 mmHg, respiratory rate 20 breaths per minute and oxygen saturation 98% while he was breathing ambient air. The sclerae were anicteric. Routine blood measurements revealed a hypochromic microcytic anemia (hemoglobin: 9.6 g/dl; hematocrit: 30%; mean corpuscular volume: 75 fl) and increased values of the classical markers of inflammation (erythrocyte sedimentation rate: 99 mm/h; C-reactive protein: 13.1 mg/l). A complete blood count, serum levels of glucose, creatinine, total protein, albumin, globulin, troponin I, creatine kinase and creatine kinase isoenzymes, lactate dehydrogenase, amylase, lipase and results of liver-function tests, and serum protein electrophoresis were normal. An electrocardiogram was normal. The patient was treated with intravenous labetalol and proton-pump inhibitors. Although symptoms, physical examination, and anemia were consistent with peptic ulcer or erosive gastritis, an esophagogastroduodenoscopy was unremarkable. The initial symptoms improved gradually during the following 24 h, although mild epigastric discomfort persisted. However, several hypertensive crises (systolic and diastolic values in a range of 180–220 and 110–140 mmHg, respectively) occurred that required labetalol infusion for 3 days. Upon labetalol withdrawal, therapy with doxazosin (16 mg daily), transdermal clonidine (10 mg weekly), atenolol (200 mg daily), spironolactone (50 mg daily), furosemide (50 mg daily), amlodipine (10 mg daily), ramipril (10 mg daily) was gradually set, still with poor blood pressure control.