Dimitris Babalis

Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake

BACKGROUND The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. OBJECTIVE We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. DESIGN After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. RESULTS Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. CONCLUSIONS The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control. This trial was registered at clinicaltrials.gov as NCT00390637.

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects

BACKGROUND Weight loss has been shown to reduce risk factors associated with cardiovascular disease and diabetes; however, successful maintenance of weight loss continues to pose a challenge. OBJECTIVE The present study was designed to assess whether changes in subcutaneous adipose tissue (scAT) gene expression during a low-calorie diet (LCD) could be used to differentiate and predict subjects who experience successful short-term weight maintenance from subjects who experience weight regain. DESIGN Forty white women followed a dietary protocol consisting of an 8-wk LCD phase followed by a 6-mo weight-maintenance phase. Participants were classified as weight maintainers (WMs; 0-10% weight regain) and weight regainers (WRs; 50-100% weight regain) by considering changes in body weight during the 2 phases. Anthropometric measurements, bioclinical variables, and scAT gene expression were studied in all individuals before and after the LCD. Energy intake was estimated by using 3-d dietary records. RESULTS No differences in body weight and fasting insulin were observed between WMs and WRs at baseline or after the LCD period. The LCD resulted in significant decreases in body weight and in several plasma variables in both groups. WMs experienced a significant reduction in insulin secretion in response to an oral-glucose-tolerance test after the LCD; in contrast, no changes in insulin secretion were observed in WRs after the LCD. An ANOVA of scAT gene expression showed that genes regulating fatty acid metabolism, citric acid cycle, oxidative phosphorylation, and apoptosis were regulated differently by the LCD in WM and WR subjects. CONCLUSION This study suggests that LCD-induced changes in insulin secretion and scAT gene expression may have the potential to predict successful short-term weight maintenance. This trial was registered at clinicaltrials.gov as NCT00390637.

Cardiac hypertrophy and characteristic impedance in spontaneously hypertensive rats

Characteristic impedance and systemic arterial compliance were evaluated in 12 anaesthetized spontaneously hypertensive rats (SHR) from analysis of phasic records of pressure and flow in the ascending aorta. Cardiac hypertrophy expressed as the ratio of the left ventricular weight to the body weight was not correlated with arterial blood pressure (systolic, diastolic or mean). In contrast, there was a significant relationship between the left ventricular weight to body weight ratio and the characteristic impedance, suggesting that increased arterial stiffness contributes to left ventricular hypertrophy in SHR.

Ventricular function and arterial compliance in patients with congestive cardiomyopathy

In order to study the interrelationship between left ventricular afterload, estimated from the mean left ventricular wall stress, and the mechanical properties of the aorta, we have simultaneously measured systemic arterial compliance and left ventricular wall stress in 19 patients with congestive cardiomyopathy. The strong linear relationship between the ejection fraction of the left ventricle and systemic arterial compliance, and between left ventricular wall stress and systemic arterial compliance, suggests that systemic arterial compliance is an important determinant of left ventricular afterload and thus of left ventricular function.

Vascular endothelium, mechanical properties of the arterial wall and local angiotensin converting enzyme inhibition

Methods: An experimental model of in situ isolated carotid arteries was used to study the contribution made by angiotensin II (Ang II) towards the mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The effects of local incubation with saralasin (Sar1-Thr8-Ang II, 10-6mol/l) and with lisinopril (5 x 10-6mol/l) on carotid compliance were compared to the effects of removing the endothelium and the effects of totally abolishing vasomotor tone with potassium cyanide (0.1 mg/ml). Results: With an intact endothelium, local incubation with lisinopril increased carotid compliance by 23% in WKY rats (P<0.05) and by 14% in SHR (P<0.01). Under the same experimental conditions, saralasin increased carotid compliance by 24% in WKY rats and 23% in SHR relative to control values (P<0.05 and P<0.001, respectively). Removal of the endothelium induced significant increases in carotid compliance in WKY rats (17%, P<0.01) and in SHR (33%, P< 0.001). After removal of the endothelium, there was no further increase in carotid compliance with lisinopril in either strain. In contrast, saralasin induced further significant compliance increases in both strains ( + 18%, P<0.001, and +11%, P<0.01, in WKY and SHR, respectively). After the artery had been poisoned with potassium cyanide, there was no further increase in compliance relative to values obtained with saralasin in either strain with or without the endothelium. Conclusions: These findings suggest that Ang II receptors have a major effect on the control of basal vasomotor tone of large arteries in both normotensive and hypertensive rats. Furthermore, the increase in carotid compliance induced by local incubation with saralasin and with angiotensin converting enzyme (ACE) inhibitors may involve similar mechanisms acting on smooth muscle angiotensin receptors.

Ebsteinʼs anomaly: a potential cause of misinterpretation of myocardial perfusion scintigraphy

We present the case of a 43-year-old woman with a history of Ebsteins anomaly, who was referred for a myocardial perfusion single-photon emission computed tomography (SPECT) study due to angina-like symptoms. Dilatation of the right ventricle and right atrium, apical displacement of the septal tricuspid leaflet, small left ventricle with good left ventricular and a moderate degree of tricuspid regurgitation with mild pulmonary hypertension were found on echocardiography. Myocardial SPECT perfusion imaging with [99m Tc]tetrofosmin demonstrated a large defect in the inferior septal wall in the stress study with mild partial reversibility at rest. Coronary angiography revealed normal coronary arteries. Histological studies have shown that these patients develop increased fibrosis in the left ventricular wall and ventricular septum, especially in the basal and middle region of the septum, which adjoins with the atrialized component of the right ventricle. This is in concordance with the findings of the myocardial perfusion scan in the case described.

Relationships between single-vessel coronary artery obstructions and wall motion dysfunction analyzed by four computer-based methods

We analyzed regional wall motion in 238 patients by using cineangiograms recorded in the 30 degrees right anterior oblique projection. The sample was divided into three groups: a normal group (n = 71), a group with isolated obstruction of the left anterior descending coronary artery and previous anterior myocardial infarction (n = 85), and a group with isolated obstruction of the right coronary artery and previous inferior myocardial infarction (n = 82). Both anterior and inferior groups also had motion abnormality within the corresponding anterior or inferior wall as judged by the qualitative analysis of cineangiograms. Four quantitative methods were compared: a long axis method and a center of mass method using internal reference systems, a method derived from the Stanford model and an area-based method using external reference systems. Normal regional values were determined from the normal group to evaluate the specificity and sensitivity of the methods. The area-based method was the most sensitive in the anterior infarction group, whereas the center of mass method was the most sensitive in the inferior infarction group. We conclude that there is no evidence that any method, among those tested, is superior to others for every expected location of wall motion abnormality.