Effects of Saturated Fat,Polyunsaturated Fat,Monounsaturated Fat,and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials

BackgroundEffects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis.ConclusionsThis meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.     

The Impact of Dietary and Metabolic Risk Factors on Cardiovascular Diseases and Type 2 Diabetes Mortality in Brazil

Background

Trends in food availability and metabolic risk factors in Brazil suggest a shift toward unhealthy dietary patterns and increased cardiometabolic disease risk, yet little is known about the impact of dietary and metabolic risk factors on cardiometabolic mortality in Brazil.

Methods

Based on data from Global Burden of Disease (GBD) Study, we used comparative risk assessment to estimate the burden of 11 dietary and 4 metabolic risk factors on mortality due to cardiovascular diseases and diabetes in Brazil in 2010. Information on national diets and metabolic risks were obtained from the Brazilian Household Budget Survey, the Food and Agriculture Organization database, and large observational studies including Brazilian adults. Relative risks for each risk factor were obtained from meta-analyses of randomized trials or prospective cohort studies; and disease-specific mortality from the GBD 2010 database. We quantified uncertainty using probabilistic simulation analyses, incorporating uncertainty in dietary and metabolic data and relative risks by age and sex. Robustness of findings was evaluated by sensitivity to varying feasible optimal levels of each risk factor.

Results

In 2010, high systolic blood pressure (SBP) and suboptimal diet were the largest contributors to cardiometabolic deaths in Brazil, responsible for 214,263 deaths (95% uncertainty interval [UI]: 195,073 to 233,936) and 202,949 deaths (95% UI: 194,322 to 211,747), respectively. Among individual dietary factors, low intakes of fruits and whole grains and high intakes of sodium were the largest contributors to cardiometabolic deaths. For premature cardiometabolic deaths (before age 70 years, representing 40% of cardiometabolic deaths), the leading risk factors were suboptimal diet (104,169 deaths; 95% UI: 99,964 to 108,002), high SBP (98,923 deaths; 95%UI: 92,912 to 104,609) and high body-mass index (BMI) (42,643 deaths; 95%UI: 40,161 to 45,111).

Conclusion

suboptimal diet, high SBP, and high BMI are major causes of cardiometabolic death in Brazil, informing priorities for policy initiatives.     

The effect of resistance level and stability demands on recruitment patterns and internal loading of spine in dynamic flexion and extension using a simple trunk model

The effects of external resistance on the recruitment of trunk muscles in sagittal movements and the coactivation mechanism to maintain spinal stability were investigated using a simple computational model of iso-resistive spine sagittal movements. Neural excitation of muscles was attained based on inverse dynamics approach along with a stability-based optimisation. The trunk flexion and extension movements between 60° flexion and the upright posture against various resistance levels were simulated. Incorporation of the stability constraint in the optimisation algorithm required higher antagonistic activities for all resistance levels mostly close to the upright position. Extension movements showed higher coactivation with higher resistance, whereas flexion movements demonstrated lower coactivation indicating a greater stability demand in backward extension movements against higher resistance at the neighbourhood of the upright posture. Optimal extension profiles based on minimum jerk, work and power had distinct kinematics profiles which led to recruitment patterns with different timing and amplitude of activation.     

Copy Number Analysis Identifies Novel Interactions Between Genomic Loci in Ovarian Cancer

Ovarian cancer is a heterogeneous disease displaying complex genomic alterations, and consequently, it has been difficult to determine the most relevant copy number alterations with the scale of studies to date. We obtained genome-wide copy number alteration (CNA) data from four different SNP array platforms, with a final data set of 398 ovarian tumours, mostly of the serous histological subtype. Frequent CNA aberrations targeted many thousands of genes. However, high-level amplicons and homozygous deletions enabled filtering of this list to the most relevant. The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11. We performed a novel co-occurrence analysis to assess cooperation and exclusivity of CNAs and analysed their relationship to patient outcome. Positive associations were identified between gains on 19 and 20q, gain of 20q and loss of X, and between several regions of loss, particularly 17q. We found weak correlations of CNA at genomic loci such as 19q12 with clinical outcome. We also assessed genomic instability measures and found a correlation of the number of higher amplitude gains with poorer overall survival. By assembling the largest collection of ovarian copy number data to date, we have been able to identify the most frequent aberrations and their interactions.     

Copper uptake induces self-assembly of 18.5 kDa myelin basic protein (MBP)

Myelin basic protein (MBP) is predominantly found in the membranes of the myelin sheath of the central nervous system and is involved in important protein-protein and protein-lipid interactions in vivo and in vitro. Furthermore, divalent transition metal ions, especially Zn²⁺ and Cu²⁺, seem to directly affect the MBP-mediated formation and stabilization of the myelin sheath of the central nervous system. MBP belongs to the realm of intrinsically disordered proteins, and only fragmentary information is available regarding its partial structure(s) or supramolecular arrangements. Here, using standard continuous wave and modern pulse electron paramagnetic resonance methods, as well as dynamic light scattering, we demonstrate the uptake and specific coordination of two Cu²⁺ atoms or one Zn²⁺ atom per MBP molecule in solution. In the presence of phosphates, further addition of divalent metal ions above a characteristic threshold of four Cu²⁺ atoms or two Zn²⁺ atoms per MBP molecule leads to the formation of large MBP aggregates within the protein solution. In vivo, MBP-MBP interactions may thus be mediated by divalent cations.     

Bioimpedance Analysis Parameters and Epicardial Adipose Tissue Assessed by Cardiac Magnetic Resonance Imaging in Patients With Heart Failure

There is increasing evidence that body composition should be considered as a systemic marker of disease severity in congestive heart failure (CHF). Prior studies established bioelectrical impedance analysis (BIA) as an objective indicator of body composition. Epicardial adipose tissue (EAT) quantified by cardiac magnetic resonance (CMR) is the visceral fat around the heart secreting various bioactive molecules. Our purpose was to investigate the association between BIA parameters and EAT assessed by CMR in patients with CHF. BIA and CMR analysis were performed in 41 patients with CHF and in 16 healthy controls. Patients with CHF showed a decreased indexed EAT (22 ± 5 vs. 34 ± 4 g/m², P < 0.001) and phase angle (PA) (5.5° vs. 6.4°, P < 0.02) compared to healthy controls. Linear regression analysis showed a significant correlation of CMR indexed EAT with left ventricular ejection fraction (LV‐EF) (r = 0.56, P < 0.001), PA (r = 0.31, P = 0.01), total body muscle mass (TBMM) (r = 0.41, P = 0.001), fat‐free mass (FFM) (r = 0.30, P = 0.02), and intracellular water (ICW) (0.47, P = 0.0003). Multivariable analysis demonstrated that LV‐EF was the only independent determinant of indexed EAT (P < 0.0001). Receiver operating characteristic curve analysis indicated good predictive performance of PA and EAT (area under the curve (AUC) = 0.86 and 0.82, respectively) with respect to cardiac death. After a follow‐up period of 5 years, 8/41 (19.5%) patients suffered from cardiac death. Only indexed EAT <22 g/m² revealed a statistically significant higher risk of cardiac death (P = 0.02). EAT assessed by CMR correlated with the BIA‐derived PA in patients with CHF. EAT and BIA‐derived PA might serve as additional prognostic indicators for survival in these patients. However, further clinical studies are needed to elucidate the prognostic relevance of these new findings.     

Arachidonic acid alleviates the detrimental effects of acetylsalicylic acid on human granulosa cells performance in vitro

Here, we investigated the biological effects of arachidonic acid (AA) in human cumulus granulosa cells (CGCs) after exposure to ASA. Cells were isolated from the follicular fluid and incubated with 0.5 mM acetylsalicylic acid (ASA) and 50 µM AA. Cell viability was analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. E₂ and P₄ levels were measured by chemiluminescence assay. Expression of genes including CYP19A1, FACN, and SCD1 was measured by real‐time polymerase chain reaction assay. Oxidative status was analyzed by monitoring glutathione peroxidase activity. The fatty acid profile was analyzed by the gas chromatography technique. Enzyme‐linked immunosorbent assay was used to measure prostaglandin E₂ (PGE₂) in CGCs after exposure to ASA and AA. Protein levels of the estrogen receptor were studied by immunofluorescence staining. Ultrastructural changes were evaluated by transmission electron microscopy imaging. ASA treatment reduced E₂ production, Cyp19a1 expression, glutathione peroxidase (GPx) activity, and estradiol receptor expression in CGCs. The addition of AA prevented the ASA‐induced E₂ reduction (p < .05) and expression of Cyp19a1. Moreover, AA increased the antioxidant capacity of CGCs exposed to ASA by promoting GPx activity (p < .05). AA increased monounsaturated fatty acid/saturated fatty acid ratio compared with the ASA group (p < .05). AA supplementation triggered the synthesis and secretion of PGE₂ in ASA‐treated CGCS (p < .05). Cytoplasmic vacuolation observed in the ASA group and treatment with AA intensified vacuolation rate. The expression of the estrogen receptor was increased after AA supplementation. Data demonstrated that AA decreased the detrimental effects of ASA on human CGCs after 72 hr.     

Effect of ionic liquids on the solution structure of human serum albumin

The effect of several ionic liquids (ILs) on the solution structure of human serum albumin (HSA) is revealed by continuous wave electron paramagnetic resonance (EPR) spectroscopy and nanoscale distance measurements with double electron-electron resonance (DEER) spectroscopy. HSA, the most abundant protein in human blood, is able to bind and transport multiple fatty acids (FAs). Using spin-labeled FA, the uptake of the FA by the protein and their spatial distribution in the protein can be monitored. The FA distribution provides an indirect yet effective way to characterize the structure of the protein in solution. Addition of imidazolium-based ILs to an aqueous solution of HSA/FA conjugates is accompanied by significant destabilization and unfolding of the protein's tertiary structure. In contrast, HSA maintains its tertiary structure when choline dihydrogenphosphate (dhp) is added. The comparison of FA distance distributions in HSA with and without choline dhp surprisingly revealed that with this IL, the FA anchoring units are in better agreement with the crystallographic data. Furthermore, the FA entry point distribution appears widened and more asymmetric than in pure buffer. These results indicate that choline dhp as a cosolvent may selectively stabilize HSA conformations closer to the crystal structure out of the overall conformational ensemble.