Obesity‐related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We ...hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (−30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7‐fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. Conclusion: A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low‐fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. (HEPATOLOGY 2011)
This study examined the effect of methylglyoxal (MGO)-derived nonenzymatic posttranslational modifications (nePTMs) on the binding affinity of S100A12 to its natural receptor for advanced glycation ...end-products (RAGE). Binding of MGO-modified S100A12 to RAGE decreased significantly with increasing MGO concentration and incubation time. Ca(2+)-induced S100A12 hexamerization was impaired only at higher MGO concentrations indicating that the loss of affinity is not predominantly caused by disturbance of ligand oligomerization. nePTM mapping showed carboxyethylation of lysine (CEL) and the N-terminus without preferential modification sites. Besides, hydroimidazolone, hemiaminals, argpyrimidine, and tetrahydropyrimidine rapidly formed at R21. Even at the highest modification rate, hexamerization of synthesized CEL-S100A12 was unaffected and RAGE-binding only slightly impaired. Thus, nePTMs at R21 seem to be the major cause of MGO-induced impairment of S100A12 oligomerization and RAGE binding.
Obesity predisposes to heart failure and premature cardiovascular death, particularly in sedentary women. In animal models and in men with type 2 diabetes mellitus, impaired cardiac function is ...associated with myocardial triglyceride (MTG) accumulation. Lipotoxic injury from altered myocardial metabolism may be causative. Whether such association also exists in obese, non-diabetic women is unknown.
To explore the relation between MTG content, cardiac remodelling and cardiorespiratory fitness in obese, insulin-sensitive and insulin-resistant non-diabetic women.
Cross-sectional investigation.
Academic clinical research centre.
65 Overweight/obese and sedentary, but otherwise healthy women (body mass index 33±4 kg/m(2); age 45±10 years).
None.
Cardiac structure and function measured by cardiovascular magnetic resonance imaging and MTG content of the interventricular septum by (1)H MR spectroscopy. Additional outcomes were cardiopulmonary fitness and insulin sensitivity during oral glucose tolerance testing.
Insulin resistance (composite insulin sensitivity index (C-ISI) <4.6) was present in 29 women. MTG content was higher (0.83±0.30 vs 0.61±0.23, p=0.002) and left ventricular diastolic (p<0.01), but not systolic function was reduced in women with insulin resistance compared with insulin-sensitive women. The remodelling index defined as left ventricular mass divided by end-diastolic volume was increased in women with impaired glucose tolerance (p=0.006). Furthermore, cardiopulmonary fitness was equal in both groups, but was inversely correlated with MTG (r=-0.28, p=0.02).
In overweight and obese women, insulin resistance is associated with increased MTG content, cardiac remodelling and reduced diastolic function.
ClinicalTrials.gov NCT00956566.
Cardiac Magnetic Resonance Monitors Reversible and Irreversible Myocardial Injury in Myocarditis Anja Zagrosek, Hassan Abdel-Aty, Philipp Boyé, Ralf Wassmuth, Daniel Messroghli, Wolfgang Utz, Andre ...Rudolph, Steffen Bohl, Rainer Dietz, Jeanette Schulz-Menger This study aimed to assess the value of cardiovascular magnetic resonance (CMR) to monitor myocarditis-related myocardial injury over the course of the disease. Thirty six patients hospitalized with acute myocarditis were studied acutely and 18 ± 10 months later. Acutely, T2 signal was elevated in 86%, global T1-signal post-contrast in 80%, and late gadolinium enhancement (LGE) was present in 63%. At follow-up, ejection fraction increased from 56% to 62% while both T2 and global T1 decreased. LGE persisted in all but one patient. Thus, the time course of signal properties in the myocardium as assessed by CMR can differentiate acute from healed myocarditis.
Aims
Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non‐invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains ...difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD.
Methods and results
We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD−, n = 26), and uncertain (DD±, n = 9). Diagnosis of DD was based on echocardiographic E/E′, invasive LV end‐diastolic pressure, and N‐terminal pro‐brain natriuretic peptide. CMR was performed at 1.5 T to assess LV and left atrial (LA) morphology, LV diastolic strain rate (SR) by tissue tracking and tagging, myocardial peak velocities by tissue phase mapping, and transmitral inflow profile using phase contrast techniques. Statistics were performed only on definitive DD+ and DD− (total number 41). DD+ showed enlarged LA with LA end‐diastolic volume/height performing best to identify DD+ with a cut‐off value of ≥0.52 mL/cm (sensitivity = 0.71, specificity = 0.84, and area under the receiver operating characteristic curve = 0.75). DD+ showed significantly reduced radial (inferolateral E peak: DD−: −14.5 ± 6.5%/s vs. DD+: −10.9 ± 5.9%/s, P = 0.04; anterolateral A peak: DD−: −4.2 ± 1.6%/s vs. DD+: −3.1 ± 1.4%/s, P = 0.04) and circumferential (inferolateral A peak: DD−: 3.8 ± 1.2%/s vs. DD+: 2.8 ± 0.8%/s, P = 0.007; anterolateral A peak: DD−: 3.5 ± 1.2%/s vs. DD+: 2.5 ± 0.8%/s, P = 0.048) SR in the basal lateral wall assessed by tissue tracking. In the same segments, DD+ showed lower peak myocardial velocity by tissue phase mapping (inferolateral radial peak: DD−: −3.6 ± 0.7 ms vs. DD+: −2.8 ± 1.0 ms, P = 0.017; anterolateral longitudinal peak: DD−: −5.0 ± 1.8 ms vs. DD+: −3.4 ± 1.4 ms, P = 0.006). Tagging revealed reduced global longitudinal SR in DD+ (DD−: 45.8 ± 12.0%/s vs. DD+: 34.8 ± 9.2%/s, P = 0.022). Global circumferential and radial SR by tissue tracking and tagging, LV morphology, and transmitral flow did not differ between DD+ and DD−.
Conclusions
Left atrial size and regional quantitative myocardial deformation applying CMR identified best patients with DD.
Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% ...body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients.
Venous mid-regional pro-ANP concentration was assessed at rest and after incremental exhaustive exercise testing before and after weight reduction. We also measured natriuretic peptide receptor A and C mRNA expression in subcutaneous adipose tissue to gauge both ANP responsiveness and clearance mechanisms.
The average weight reduction of 9.1 ± 3.8 kg was associated with reductions in visceral and subcutaneous abdominal fat mass, liver fat content, insulin resistance, and ambulatory blood pressure. However, mid-regional pro-ANP plasma concentrations were unchanged with weight loss (51 ± 24 vs. 53 ± 24 pmol/l). Exercise elicited similar acute mid-regional pro-ANP increases before and after weight loss. Adipose tissue natriuretic peptide receptor type A mRNA expression remained unchanged, whereas natriuretic peptide receptor type C mRNA decreased with weight loss.
We conclude that physical exercise acutely increases ANP release in obese patients, whereas modest diet-induced weight loss primarily affects ANP clearance mechanisms. Interventions combining weight loss and regular physical exercise may be particularly efficacious in reversing obesity-associated relative natriuretic peptide deficiency.
Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and ...complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the intrinsic activity of the regioisomers investigated is controlled by the ability of the heterocyclic unit to interact with both elements of the D4 binding-site crevice, the aromatic microdomain in TM6, and a serine residue in TM5.
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