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

Maternal Exercise Activates Genes Associated with Mitochondrial Biogenesis in Fetal Myocardium of Mouse

Maternal exercise during pregnancy has been shown to improve long-term metabolic health on offspring in later life. Mitochondria are the critical site of metabolism, and are inherited by maternal origin. However, the effects of maternal exercise during pregnancy on fetal mitochondrial biogenesis are not well understood. PURPOSE: To test whether maternal exercise can activate genes associate with mitochondrial biogenesis in the fetal heart. METHODS: Female C57BL/6 mice were divided into sedentary and exercise groups. The mice in the exercise group were exposed to voluntary cage-wheel from gestational day 1 through 17, at which time they were sacrificed. Litter size and individual fetal weights (3 days before birth) were taken when pregnant dams were sacrificed. All fetuses were sexed and two to three hearts from same sex within the group were pooled to study gene expression: all data were presented by group since there was no sex difference within group. RESULTS: Exercise dams ran an average of 7.22 ± 0.41km/day until mid-pregnancy and gradually decreased to low levels (1.39 ± 0.43 km/day) through the remainder of gestation. Weight gain during pregnancy was not significantly different between exercise (14.45 ± 0.99g) and sedentary (15.99 ± 1.13g) pregnant dams. There were no significant differences in litter size, sex distribution, and average fetal body weight per litter between sedentary and exercise dams. Genes associated with mitochondrial biogenesis, including Ppargc1a (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), Nrf1 (nuclear respiratory factor-1), and Nrf2 (nuclear respiratory factor-2) were significantly upregulated in fetuses from exercise dams. CONCLUSION: Although total kilometers run per day (km/day) were significantly decreased in later stage of pregnancy, maternal exercise initiated at day 1 of gestation significantly increased genes associated with mitochondria biogenesis, indicating that maternal exercise enhances mitochondrial biogenesis and mitochondrial function

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

Does one bout of high intensity resistance training change circulatory levels of Irisin?

The recently novel identified myokine, irisin, has gained attention as a way to increase energy expenditure by enhancing metabolic function. Exercise and active lifestyle increase the synthesis of contraction-regulated myokines that have direct effect on cells metabolism. PURPOSE: The objective of this study is to analyze the effects of one bout of high intensity exercise on circulatory levels of irisin in healthy young adults. METHODS: A total of 24 participants (age 21.3 ± 2.1 years, body mass index [BMI] 22.12 ± 1 kg/m2, lean body mass [LBM] 46 ± 10.1 kg, and relative body fat [%BF] 25.9 ± 9.9) were recruited. Subjects were blocked by sex, BMI, LBM, and %BF content and randomized to either control (n=13) or intervention (n=11). Physical Fitness was assessed by means of dual-energy x-ray absorptiometry (DXA), strength tests (Bench press and Leg press one repetition maximum [1RM]), and cardiopulmonary maximal stress test. Blood samples were collected to assess irisin at baseline, during (45 minutes), and post-intervention. RESULTS: Irisin (ul/ml) levels for control and intervention groups were 6.1 ± 1.7 and 5.77 ± 0.9 at baseline, 5.6 ± 1.3 and 6.03 ± 1 at 45-min, and 6.3 ± 1.9 and 5.8 ± 1.1 at post respectively. Interaction effect (time x intervention) was close to statistical significance (F[2,44]=3.106, p=0.055), and time (F[2,44]=0.837, p=0.440) and intervention (F[1,22]=0.091, p=0.766) factors were not significant. CONCLUSIONS: In addition to heterogeneous research findings, the lack of changes on serum concentrations of irisin after intervention shown in this study adds controversial results to the literature. Furthermore, values obtained on irisin concentrations in the control group resulted in more questions rather than answers. We hypothesize that, if irisin is an exercise-induced hormone, other confounding variables such as room temperature, or body temperature might be critical factors to control for future studies

Effects of Acupuncture, Electroacupuncture, and Electrostimulation Treatments on Plantaris by Casting Model

It is essential to seek the therapeutic strategy for attenuating muscle atrophy because muscle atrophy diminishes the quality of life. Acupuncture and electrostimulation have been used as a therapeutic intervention to control pain under pathological conditions. However, little is known about the effects of acupuncture and electrostimulation on skeletal muscle mass and function. PURPOSE: To test whether acupuncture, electroacupuncture, and electrostimulation affect muscle mass and contractile properties METHODS: Forty female Sprague Dawley rats were randomly divided into 5 groups: 1) Control (CON), 2) Cast (CT), 3) CT+ Acupuncture (AC), 4) CT+ Electroacupuncture (EA), and 5) CT+ Electrostimulation (ES) (n=8 each). The plaster casting material was wrapped from the trunk to the middle of one hind paw. Acupuncture and Electro-Acupuncture treatment (2-15 Hz, 2-4 Voltage) was applied by needling ST36 and GB34 (acupoints). Electrostimulation (2-15 Hz, 2-4 Voltage) was conducted by needling in the lateral and medial Gastrocnemius. All treatments were conducted 15 minutes with 3 times/wk for 14 days. Two major atrophy markers, muscle-specific E3 ubiquitin ligases, MAFbx/atrogin1 and muscle ring Finger -1 (MuRF1), were measured using the Western blot method. Data were analyzed using one-way ANOVA with the Least Significant Difference post hoc test. RESULTS: After 2 weeks of casting, plantaris showed significant atrophy in CT compared to the CON group (143.94±13.08 vs. 223.9±20.93 mg; p\u3c0.05). MAFbx/atrogin1 and MuRF1 were significantly increased with CT, while decreased with treatments (AC, EA, and ES). The peak twitch tension was significantly decreased in CT, while increased in AC and ES. However, AC, EA, ES did not alleviate muscle atrophy associated with casting. CONCLUSION: Acupuncture and electrostimulation can be used as effective therapeutic interventions for decreased muscle strength that is associated with casting-induced muscle atrophy

Impact of time to treatment of oseltamivir on influenza hospitalization cost among Korean children

BackgroundAlthough oseltamivir is a common influenza treatment, there is a lack of data on the economic benefits of timely oseltamivir treatment.MethodsFrom February 2004 through June 2007, 116 hospitalized children ≤15 years of age with laboratory‐confirmed influenza who received oseltamivir were identified via retrospective medical chart review. Demographic, clinical, and cost data were abstracted and multivariate linear regression was used to assess the association between oseltamivir time to treatment and treatment‐related costs among hospitalized children with laboratory‐confirmed influenza.ResultsOverall, 28% (n = 33) of patients were treated with oseltamivir ≥day 3 of admission. Rapid influenza diagnostic test was used in a significantly lower proportion of patients treated with oseltamivir ≥day 3 of admission compared with those who received oseltamivir earlier. On multivariate linear regression, initiation of oseltamivir ≥day 3 of admission was associated with a 60.84% increase (95%CI: 32.59–95.11) in treatment‐related hospital costs, compared with initiation on admission.ConclusionDelayed initiation of oseltamivir was found to be associated with increased treatment‐related hospital costs among children hospitalized with laboratory‐confirmed influenza.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111958/1/ped12526.pd

Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo

Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10-30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesisclos

Nitrous oxide-induced NO-dependent neuronal release of β-endorphin from the rat arcuate nucleus and periaqueductal gray

Nitrous oxide (N 2O)-induced antinociception is thought to result from nitric oxide (NO)-dependent neuronal release of endogenous opioid peptides in the central nervous system. The present study employed microdialysis to determine whether exposure to N 2O stimulates proopiomelanocortin (POMC) neurons to release β-endorphin in the arcuate nucleus (ARC) of the hypothalamus and the periaqueductal gray (PAG) of the midbrain. Male Sprague–Dawley rats were stereotaxically implanted with microdialysis probes in the ARC or PAG. Exposure to 70% N 2O significantly increased dialysate levels of oxidation products of NO as well as β-endorphin, compared to levels in fractions collected under room air. These increases in the ARC and PAG were abolished by systemic pretreatment with l-N G-nitro arginine methyl ester ( l-NAME). These findings suggest an association between increased NO activity and the stimulated release of β-endorphin during exposure of rats to N 2O. ►N 2O increases extracellular levels of nitrite and nitrate in the ARC and PAG. ►N 2O increases extracellular levels of β-endorphin in the ARC and PAG. ►These increases are both reversed by pretreatment with a NOS-inhibitor