Effects of High Fat Diet and Exercise on the Metabolism of Maternal Hearts during Pregnancy

Obesity has become a major concern for developed nations across the world, and the United States is the country which is most affected by this pandemic. Excess adiposity is known to cause chronic inflammation, diabetes, cancer, and cardiovascular disease: the leading cause of death for over a decade. With many women of reproductive age considered overweight or obese, the association between obesity and metabolic disorder is concerning. Positive metabolic health outcomes of offspring due to maternal exercise have been documented; however, little is known about how maternal exercise modifies high fat diet associated metabolic dysregulation upon mothers during gestation. The aim of our study was to determine whether maternal exercise before and during pregnancy would alleviate high fat diet-associated glucose and insulin resistance in high fat fed pregnant mice. Using C57BL/6 virgin female mice as a model, we fed the animals either a low fat diet (LFD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for twelve weeks, with an exercise intervention after four weeks (HFD+Ex), and pregnancy initiation after eight weeks of diet consumption. Glucose and insulin tolerance tests were performed at day 15 of gestation. Prescribed diet and exercise (or sedentary) behavior continued throughout pregnancy until animals were sacrificed at the 19th day of gestation. The HFD animals experienced a significant increase in body weight, along with increased numbers of calories consumed per day, and exercise further increased body weight and food intake. Both the HFD and the HFD+Ex animals displayed impaired glucose and insulin tolerance testing when compared with the LFD animals. Interestingly, exercise improved serum insulin levels at termination. mRNA expression of genes involved in fatty acid and glucose metabolism were upregulated in the HFD+Ex animals compared with the HFD mice. Our study exhibits that the development of adiposity from the consumption of a high fat diet prior to pregnancy leads to detrimental maternal effects during late gestation, including higher body weight, and glucose tolerance. Surprisingly, the addition of exercise did not alter dam morphology or gestational glucose tolerance; however, it did improve serum insulin levels and metabolite handling in the heart

Exercise Before and During Pregnancy Does Not Alter Myosin Heavy Chain Isoforms in Pregnant Mice

The myosin heavy chain isoforms (β-MHC and α-MHC) determine shortening velocity and power output properties of the heart. There are two types of cardiac hypertrophy, pathological and physiological. Pathological cardiac hypertrophy is often accompanied by re-expression of β-MHC with decreases in kinetic properties of the heart. High fat diet is known to lead to cardiac dysfunction seen through the expression of β-MHC in the heart. However, little is known about the effects of high fat diet and exercises during pregnancy on MHC isoform content. The purpose of this study is to determine whether exercise in combination with high fat diet consumption before and during pregnancy would alter MHC isoforms. Our model consisted of C57BL/6 virgin female mice whom were first split into high fat diet (HFD, 45% kcal) and low fat diet (LFD 10% kcal) groups. Four weeks before pregnancy initiation, the HFD mice were split into two sub groups, sedentary (HFD) or exercised (HFD+Ex). The HFD+Ex participated in voluntary wheel running through gestation. All mice were sacrificed at 19 days gestation. The MHC isoform content of ventricular homogenates was determined using a 6% SDS-Polyacrylamide gel electrophoresis. We found, there were no differences in MHC isoform expression between the HFD, HFD+Ex group, and the LFD animals. We conclude that exercise before and during pregnancy does not alter MHC isoform content in pregnant mice fed by high fat diet

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Time Course Of Short-Term Hypertrophy In The Absence Of Eccentric Muscle Damage

Background: It has been proposed that the increase in skeletal muscle mass observed during the initial weeks of initiating a resistance training program is concomitant with eccentric muscle damage and edema. Purpose: We examined the time course of muscle hypertrophy during 4 weeks of concentric-only resistance training. Methods: Thirteen untrained men performed unilateral concentric-only dumbbell curls and shoulder presses twice per week for 4 weeks. Sets of 8–12 repetitions were performed to failure, and training loads were increased during each session. Subjects consumed 500 ml of whole milk during training. Assessments of soreness, lean mass, echo intensity, muscle thickness, relaxed and flexed arm circumference, and isokinetic strength were performed every 72 or 96 h. Results: Soreness, echo intensity, relaxed circumference, and peak torque data did not significantly change. Significant increases in lean mass, muscle thickness, and flexed circumference were observed within seven training sessions. Lean mass was elevated at tests #7 (+109.3 g, p =.002) and #8 (+116.1 g, p =.035), with eight different subjects showing changes above the minimal difference of 139.1 g. Muscle thickness was elevated at tests #6 (+0.23 cm, p =.004), #7 (+0.31 cm, p \u3c.001), and #8 (+0.27 cm, p \u3c.001), with ten subjects exceeding the minimal difference of 0.24 cm. There were no changes for the control arm. Conclusion: In individuals beginning a resistance training program, small but detectable increases in hypertrophy may occur in the absence of eccentric muscle damage within seven training sessions

Geranylgeraniol and Green Tea Polyphenols Mitigate Negative Effects of a High-Fat Diet on Skeletal Muscle and the Gut Microbiome in Male C57BL/6J Mice

Natural bioactive compounds are proposed as alternatives in mitigating obesity-associated skeletal muscle dysfunction. The objective of this study was to test the hypothesis that the combination of geranylgeraniol (GGOH) and green tea polyphenols (GTPs) can alleviate high-fat-diet (HFD)-induced muscle atrophy and alter gut microbiome composition. Male C57BL/6J mice fed an HFD were assigned to four groups (12 mice each) in a 2 (no GGOH vs. 400 mg GGOH/kg diet) × 2 (no GTPs vs. 0.5% weight/volume GTPs in water) factorial design. After 14 weeks of diet intervention, skeletal muscle and cecal samples were collected and examined. Compared to the control groups, the group that consumed a combination of GGOH and GTPs (GG + GTPs) had significantly decreased body and fat mass but increased skeletal muscle mass normalized by body weight and cross-sectional area. In soleus muscle, the GG + GTP diet increased citrate synthase activity but decreased lipid peroxidation. Gut microbiome beta-diversity analysis revealed a significant difference in the microbiome composition between diet groups. At the species level, the GG + GTP diet decreased the relative abundance of Dorea longicatena, Sporobacter termitidis, and Clostridium methylpentosum, and increased that of Akkermansia muciniphila and Subdoligranulum variabile. These results suggest that the addition of GGOH and GTPs to an HFD alleviates skeletal muscle atrophy, which is associated with changes in the gut microbiome composition

A comparison of methods used to unveil the genetic and metabolic pool in the built environment

Abstract Background A majority of indoor residential microbes originate from humans, pets, and outdoor air and are not adapted to the built environment (BE). Consequently, a large portion of the microbes identified by DNA-based methods are either dead or metabolically inactive. Although many exceptions have been noted, the ribosomal RNA fraction of the sample is more likely to represent either viable or metabolically active cells. We examined methodological variations in sample processing using a defined, mock BE microbial community to better understand the scope of technique-based vs. biological-based differences in both ribosomal transcript (rRNA) and gene (DNA) sequence community analysis. Based on in vitro tests, a protocol was adopted for the analysis of the genetic and metabolic pool (DNA vs. rRNA) of air and surface microbiomes within a residential setting. Results We observed differences in DNA/RNA co-extraction efficiency for individual microbes, but overall, a greater recovery of rRNA using FastPrep (> 50%). Samples stored with various preservation methods at − 80°C experienced a rapid decline in nucleic acid recovery starting within the first week, although post-extraction rRNA had no significant degradation when treated with RNAStable. We recommend that co-extraction samples be processed as quickly as possible after collection. The in vivo analysis revealed significant differences in the two components (genetic and metabolic pool) in terms of taxonomy, community structure, and microbial association networks. Rare taxa present in the genetic pool showed higher metabolic potential (RNA:DNA ratio), whereas commonly detected taxa of outdoor origins based on DNA sequencing, especially taxa of the Sphingomonadales order, were present in lower relative abundances in the viable community. Conclusions Although methodological variations in sample preparations are high, large differences between the DNA and RNA fractions of the total microbial community demonstrate that direct examination of rRNA isolated from a residential BE microbiome has the potential to identify the more likely viable or active portion of the microbial community. In an environment that has primarily dead and metabolically inactive cells, we suggest that the rRNA fraction of BE samples is capable of providing a more ecologically relevant insight into the factors that drive indoor microbial community dynamics

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases : subgroup analyses of the RESTART randomised, open-label trial

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627. Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05). Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision. Funding: British Heart Foundation