bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraventricular Nucleus Over Activation Is A Critical Driver In The Development Of Neurogenic Hypertension
Authors: Basting Tyler , Sriramula Srinivas , Epling Joel , Lazartigues Eric 
Published: June 2021

Rationale and objectivesIn conscious mammals the importance of neural control over sympathetic tone in relation to cardiovascular (CV) function is well established. Neuro‐CV dysregulation leads to increased sympathetic activity and neurogenic hypertension. The paraventricular nucleus (PVN) of the hypothalamus is currently viewed as one of the key hubs for BP control and is implicated in producing or relaying the increased sympathetic tone in hypertension. We hypothesize that it is through chronic over excitation of the glutamatergic PVN neurons that this central sympathetic drive is originating. We test this theory by examining how stimulation or lesioning of the excitatory PVN neurons in conscious mice affects blood pressure and sympathetic activity.Results & ConclusionGlutamatergic PVN neurons were unilaterally transduced with channelrhodopsin2 using an adeno‐associated virus (CamKII‐ChR2‐eYFP‐AAV2) in wildtype mice (N = 7). We then measured the effect of acute stimulation of excitatory PVN neurons selectively on resting blood pressure (DSI telemetry) in conscious mice. Stimulation of the PVN glutamatergic population resulted in an immediate frequency dependent (2 Hz, 10Hz, 20Hz) increase in blood pressure from baseline by ~10 mmHg at 20 Hz stimulation (p<0.001). Additionally, in vGlut2‐cre mice glutamatergic neurons of the PVN were bilaterally lesioned utilizing a cre‐dependent caspase (Dio‐Caspase‐AAV). We then recorded resting blood pressure and urinary norepinephrine levels in conscious mice before and after DOCA‐Salt hypertension. Quantified glutamatergic lesions of the PVN (39.3%, p<0.05) resulted in a blunted rise in BP when animals went through the DOCA‐salt protocol (p<0.05 at 7 day time point, N = 8). Finally, we measured nor‐epinephrine levels as a quantification of sympathetic activity between the lesion group and widtype group and observed a significant reduction after DOCA‐salt induced hypertension in the lesioned animals (p<0.05). These experiments demonstrate that stimulation of the PVN is sufficient to cause autonomic dysfunction. Additionally, the dysautonomia observed in neurogenic hypertension is due, in part, to over activation in the PVN.Support or Funding InformationHL093178‐07, HL135635‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Myo‐inositol in Ischemic Stroke Outcome in a Type 2 Diabetic Mouse Model
Authors: Villalba Heidi , Vaidya Bhuvaneshwar , Abbruscato Thomas 
Published: June 2021

Stroke is the leading cause of disability in the United States; ischemic stroke is the common form that occurs in 87% of all strokes. It has been reported that an increase in brain edema after ischemic stroke worsens long‐term clinical outcome. Myo‐inositol (MI), a major organic osmolyte that promotes cell membrane stability and various cellular functions, has been reported to be detected at lower brain levels in stroke patients. Furthermore, glucose can compete with MI transport which could lead to further lowering of brain levels of MI in diabetic patients which is compounded with higher brain edema reported in diabetic stroke patients. Therefore, understanding the relationship between MI and diabetic stroke injury is vital. In this study, we investigated the role of MI transporters during stroke and post‐stroke outcomes especially related to the role of glial cells and post‐stroke reorganization. Our hypothesis is that MI plays a putative role in recovery of motor function after stroke. Restoration of activity in the primary motor cortex has been associated with better motor function in stroke patients. Primary astrocytes were used for in vitro studies and middle cerebral artery occlusion (MCAO) mouse model for in vivo stroke studies. Immunocytochemistry (ICC) studies showed that astrocytes express sodium dependent myo‐inositol transporter 1 (SMIT1) and sodium‐dependent glucose transporter 6 (SGLT6) transporters and level of expression changed in a time‐dependent manner during oxygen‐glucose deprivation (OGD). Further, this was confirmed by time‐dependent uptake of MI during normoxic and OGD conditions. Preliminary animal studies demonstrated that post‐stroke administration of MI attenuated infarction size and edema ratios in a db/db mouse model of type 2 diabetes compared to nondiabetic ischemic animals and also improved motor function in behavioral tests. This preliminary data suggests that myo‐inositol may have a neuroprotective role in ischemic stroke injury and could significantly improve stroke outcome. More studies are required to understand the neuroprotective mechanisms of MI in stroke injury.Support or Funding InformationRO1 NS070612This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dexmedetomidine Modification of the Chemoreflex Response to Severe Arterial Hypoxia in the Rabbit
Authors: Quail Anthony , Ravindran Bhavi , Cottee David , Johnstone Janice , White Saxon 
Published: June 2021

The carotid body contains alpha‐2 adrenoceptors but selective agonists given during hypoxia have shown inhibition or enhancement of carotid sinus nerve activity in vivo (1), and in vitro (2). Dexmedetomidine (DM) is a highly‐selective alpha‐2 adrenergic agonist currently used for clinical sedation and analgesia (3,4) but its effects on integrated chemoreflex control during hypoxia are unknown. We examined the hypothesis that DM would selectively alter components of the cardiorespiratory responses to severe arterial hypoxia (PaO2 <35 mm Hg). An ear artery and vein of 6 New Zealand White female rabbits were cannulated (lidocaine 2%). Mean arterial pressure (AP), arterial blood gases, heart rate (HR), minute ventilation (VE), tidal volume (VT), respiratory frequency (f) and oxygen saturation (ear SpO2) were measured breathing room air, followed by 5 minutes of hypoxia (FiO2 7–8%). After a one‐hour recovery period, the measurements were repeated during intravenous DM infusions (4 or 40 mcg/kg/hr), breathing room air followed by exposure to a matched hypoxic stimulus. One dose of DM was studied on each of two experimental days, one week apart. Behavioural responses were recorded before and during DM infusions. Data were analysed using two‐way repeated measures ANOVA. Significant differences were accepted at the p<0.05 level. In the absence of DM, hypoxia alone evoked a reflex fall in HR and f, with increases in VT, VE and AP. In rabbits breathing room air, DM alone caused dose‐dependent falls in f, VE, HR and AP, while VT was unchanged. With DM plus hypoxia, the reflex bradycardia was absent at the higher dose. The increase in VT remained intact during both doses, while the rise in VE was attenuated due to an unchanged f. The AP increased from a lowered baseline. DM produced dose‐dependent sedation. We conclude reflex vagal control of heart rate during severe hypoxia is modified by DM. There are dose‐dependent effects on AP and components of ventilation. The increase in VT in response to hypoxia during DM infusion indicates that chemotransduction at the carotid body is intact. The data suggest the main sites of action of dexmedetomidine on cardiorespiratory control during hypoxia are within the CNS and not at the carotid body.Support or Funding InformationJohn Hunter Hospital Charitable Trust and Hunter Medical Research InstituteThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of local Interleukin‐6 on Skeletal Muscle Mitochondrial Physiology
Authors: Abid Hinnah , Hart Corey , Lanza Ian 
Published: June 2021

Skeletal muscle is vital to metabolic health and physical function. Skeletal muscle mitochondria have been extensively interrogated as organelles whose function and dysfunction are closely tied with chronic diseases such as diabetes and sarcopenia. There is accumulating evidence suggesting that chronic inflammation that is prevalent with aging and obesity is associated with skeletal muscle abnormalities such as functional impairments in mitochondria. Despite compelling links between inflammation, oxidative stress, and skeletal muscle dysfunction, the local effects of inflammatory cytokines on skeletal muscle mitochondrial physiology are currently not well‐understood. The purpose of this study was to determine how the inflammatory cytokine interleukin‐6 (IL‐6) influences skeletal muscle mitochondrial function. To determine the acute effects of IL‐6, mitochondria were isolated from skeletal muscle of healthy male mice (C57BL6) and were exposed to IL‐6 (IL6+,50 ng/ml) or vehicle (CTRL) for one hour. Multiplexed measurements of mitochondrial respiration (high‐resolution respirometry) and reactive oxygen species production (ROS, fluorometry) revealed that IL‐6 significantly increased ROS production as a percent of oxygen (4.14%±0.40) compared to CTRL (2.74%±0.34). Similarly, IL‐6 increased ROS production in differentiated C2C12 myotubes that were incubated for 18 hrs with 50 ng/mL IL‐6 (4.71%±.57) compared to CTRL (2.21%±.34). To evaluate the possibility that IL‐6 triggers ROS production by stimulating the mitochondrial transition pore (mPTP), isolated mitochondria were ale treated with cyclosporin A (CsA), a mPTP inhibitor in the presence or absence of IL‐6. Inhibition of mPTP attenuated IL‐6 induced ROS production (IL6+ (4.14%±0.40) vs. IL6+/CsA (2.78%±0.58). These results suggest that IL‐6 triggers an increase in mitochondrial ROS production that appears to be mediated by opening of the mPTP. Prolonged opening of the mPTP caused by chronically elevated IL‐6 may contribute to increased oxidative stress that is evident in skeletal muscle with aging and obesity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Urocortin 2 gene transfer reduces fasting glucose, polydipsia, hyperphagia and increases body weight in type 1 diabetes
Authors: Bhargava Raag , Tay May Ling , Gao Meihua , Hammond HK 
Published: June 2021

We previously have shown that a single intravenous (IV) injection of Adeno‐associated Virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal and insulin sensitivity in insulin resistant mice (type‐2 diabetes). The current study tests the hypothesis that UCn2 gene transfer is effective in type‐1 diabetes. We used insulin‐deficient Akita mice and assessed water and food consumption, body weight and fasting glucose before and after UCn2 gene transfer. Akita mice (n=50; 21.3±1.5 g; 2.4±0.2 months of age) were used. Sixteen mice with a mean pre‐treatment 12‐hr fasting glucose of 322±80 mg/dL, received either AAV8.UCn2 (5×1011 genome copies, gc, IV; n=8) or Saline (IV; n=8). Fasting glucose was repeated 8 weeks after gene transfer. Thirty‐four additional mice were used to assess water and food intake and body weight before and 8w after UCn2 gene transfer (5×1011gc, IV; n=17) or Saline (IV; n=17).Fasting glucoseBefore randomization, 12‐hour fasting glucose was similar (Saline: 354±60 mg/dL, n=8; UCn2: 289±88 mg/dL, n=8; p=.11). Eight weeks after treatment, mice that received UCn2 gene transfer showed lower fasting glucose (Saline: 272±69 mg/dL, n=8; UCn2: 106±33 mg/dL, n=8; p<.0001).Water/food intake and body weightWater intake over the 8w course of the study was reduced after UCn2 gene transfer (Saline: 1.15±0.09 ml/day/g; UCn2: 0.63±0.05 ml/day/g; p<.0001) (Fig 1). Food intake over 8w was also reduced by UCn2 gene transfer (Saline: 0.32±0.04 g/day/g; UCn2: 0.22±0.02 g/day/g; p<.0001) (Fig 1). Body weight increased 8w after UCn2 gene transfer (Saline: 24.1±1.0 g; UCn2: 27.8±0.7 g; 2‐way ANOVA p<.0001) (Fig 2).ConclusionUCn2 gene transfer reduces fasting blood glucose and reduces food and water intake. Despite reduced food intake, Akita mice that received UCn2 gene transfer showed increased body weight. These data suggest a possible non‐insulin therapy for type‐1 diabetes.Support or Funding InformationI01 BX003774 VA Merit Grant; R42HL122038 NHLBIThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Altered Body Composition does not Fully Account for Impaired Glucose Tolerance in Women with Spinal Cord Injury
Authors: Li Jia , Hunter Gary R. , Chen Yuying , McLain Amie , Smith Daniel L. , Yarar‐Fisher Ceren 
Published: June 2021

ObjectiveTo investigate the differences in insulin sensitivity and glucose tolerance among women with spinal cord injury (SCI) in comparison to their able‐bodied (AB) counterparts after adjusting for differences in body composition.DesignCross‐sectional study. Following an overnight fast, each participant consumed a 75‐g glucose solution for oral glucose tolerance test (OGTT). Blood glucose, insulin, and C‐peptide concentrations were analyzed before and 30‐, 60‐, and 120‐minute post‐consumption. Insulin sensitivity index (ISI) was estimated using the Matsuda index. Percentage fat mass (%FM) and relative skeletal muscle index (RSMI) were estimated using data from dual‐energy X‐ray absorptiometry. Visceral fat (VF) was estimated using computerized tomography (CT). Outcome measures were compared among groups using ANCOVA with %FM, VF and RSMI as covariates.SettingResearch UniversityParticipantsWomen with SCI (tetraplegia: n=8; paraplegia: n=14) and their body mass index‐and age‐matched AB counterparts (n=20).InterventionsNot applicable.ResultsAt fasting, there was no difference in glucose homeostasis (glucose, insulin, and C‐peptide concentrations) among 3 groups of women. In contrast, glucose, insulin, and C‐peptide concentrations at OGTT 120 min were higher in women with tetraplegia vs. women with paraplegia and AB women (P < 0.05, adjusted for RMSI and %FM). In addition, women with tetraplegia had lower ISI (P < 0.05, adjusted for RMSI and %FM) vs. AB women. These differences remained after adjusting for VF and RSMI.ConclusionOur study confirms that while alterations in body composition may contribute to metabolic deficits in women with SCI, it does not fully account for impaired glucose homeostasis in women with tetraplegia.Support or Funding InformationThis work was supported by the NIH under Grant K12 HD001402/HD/NICHD NIH (Chen), M01 RR000032/RR/NCRR NIH (Chen), NIDLRR – DHHS‐Administration for Community Living Sponsor award 02‐90SI501901 The University of Alabama at Birmingham Spinal Cord injury Model System (McLain).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In Utero Exposure To Cigarette Smoke Promotes Cardiac Dysfunction In High‐fat Fed Mice
Authors: Xia Huijing , Rodrigues Samya Lima , Ronis Martin J. , Noel Alexandra , Penn Arthur , Pullium Casey , Gardner Jason , Varner Kurt J. 
Published: June 2021

Maternal smoking during pregnancy is associated with an increased risk for metabolic syndrome, a risk factor for heart disease. In this study, we investigated whether in utero exposure to second hand cigarette smoke would adversely affect cardiac structure/function in the exposed offspring fed a high‐fat diet. Pregnant mice (C57B1/6J) were exposed to cigarette smoke or air (4 hr/d) on gestational days 6–19. The male offspring (age: 35 days) from the smoke and air exposure groups were fed either normal chow, or high‐fat liquid diet (35% of fat; HFD) for 16 weeks (n=12/group). Cardiac function was measured by echocardiography at baseline (30 days) and at the end of pair feeding. Mice were then sacrificed and heart tissue collected for histological analysis. At baseline, left ventricular internal diameter at end systole was significantly greater in the smoke‐exposed compared to the air group (3.2±0.1 vs 2.8±0.1 mm, P<0.05). All other baseline echocardiographic parameters were similar between the groups. 16 weeks of HFD feeding significantly increased the body weight and heart weight/tibial length in both the air and smoke‐exposed mice (P<0.05, smoking+HFD vs. smoking+chow; air+HFD vs. air+chow). However, there was no significant difference in body weight or heart weigh/tibial length between the smoking+HFD and air+HFD groups. Compared to air+HFD mice, smoking+HFD mice had significantly decreased left ventricular internal diameters and volumes during diastole (3.95±0.09 vs. 4.34±0.24 mm; 67.8±1.5 vs. 85.4±4.4 μl, P<0.05) and systole (2.91±0.07 vs. 3.34±0.15 mm; 32.5±1.9 vs. 46.3±5.1 μl, P<0.05), accompanied by increases in left ventricular wall during diastole (0.72±0.03 vs. 0.66±0.03 mm, P<0.01) and septal thickness during systole (1.2±0.06 vs. 0.99±0.05 mm, P<0.05) and increased fractional shortening. There was also increased collagen in the hearts of the smoking+HFD mice. These data indicate the development of concentric cardiac hypertrophy in smoking+HFD mice. We conclude that in utero exposure to second hand cigarette smoke produces differential cardiac responses following challenge with obesogenic high fat diet.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Negative energy balance up‐regulate the levels of hepatokines in dairy cows during the peripartum period
Authors: WANG Jianguo , LIU Lei , ZHAO Baoyu 
Published: June 2021

IntroductionThe periparturient period is vitally important to the health status and the reproductive performance of dairy cows. Negative energy balance (NEB) is considered as the pathological basis of energy metabolic disorders. Serum non‐esterified fatty acids (NEFA) and β‐hydroxybutyrate (BHBA) concentrations are the indicators of energy balance status. Angiopoietin‐like protein 4 (ANGPTL4) and fibroblast growth factor 21 (FGF21), known as hepatokines, play essential roles in lipid metabolism. However, in vivo the kinetics of ANGPTL4 and FGF21 are not entirely clear of dairy cows, particularly in dairy cows with ketosis and fatty liver. The purposes of this project were to evaluate the variations in serum concentrations of ANGPTL4 and FGF21 in periparturient dairy cows, and to examine the correlations between serum NEFA, BHBA concentrations and ANGPTL4, FGF21 concentrations, respectively, in the serum of experimental cows. Moreover, the serum concentrations of hepatokines from cows with spontaneous ketosis and fatty liver, and healthy cows were compared.MethodsExperiment IBlood parameters were measured in healthy periparturient Holstein cows from 4 wk antepartum to 4 wk postpartum (n=219). In this experiment, weekly blood samples were obtained from 4 wk before the expected calving date to 4 wk after calving.Experiment IIBlood parameters were measured in healthy cows (n=30), cows with ketosis (n=29) and fatty liver (n=25) within the first 4 wk of lactation. In this present study, all blood samples were collected from the coccygeal vein in the early morning before feeding.ResultsSerum concentrations of ANGPTL4 and FGF21 peaked at parturition, and declined rapidly over the following 2 wk. Serum ANGPTL4 and FGF21 concentrations were positively correlated with serum NEFA concentration (ANGPTL4 and NEFA: r=0.856, P=003; FGF21 and NEFA: r=0.848, P=0.004). However, the correlations between serum BHBA concentration and the serum concentrations of ANGPTL4 and FGF21 were not observed in experimental cows. Cows with ketosis and fatty liver had significantly higher serum concentrations of ANGPTL4 and FGF21 when compared with healthy cows (P<0.01).ConclusionSerum concentrations of ANGPTL4 and FGF21 were elevated during peripartum period in dairy cows, demonstrating that the energy balance changes that were associated with parturition contributed significantly to these effects. We propose that blood ANGPTL4 and FGF21 concentrations could be used as supplementary biomarkers of “energy balance” status in postpartum dairy cows. Although FGF21 and ANGPTL4 could play important roles in the adaptation of energy metabolism, they may be involved in the pathological processes of energy metabolism disorders of dairy cows in the peripartum period.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Activation of lipogenesis by hematopoietic‐ and neurologic‐expressed sequence1 stimulates hepatocellular carcinoma cell proliferation and metastasis
Authors: Jin Hua , Kim Soo Mi 
Published: June 2021

Hepatocellular carcinoma (HCC) is the second most common cause of cancer‐related mortality worldwide and its five‐year survival rate is less than 12%. Since it has been reported that hematopoietic‐ and neurologic‐expressed sequence1 (HN1) gene is upregulated in various cancers, its functional significance in HCC remains unclear. Thus, we investigated the biological role of HN1 in HCC using HepG2 and SNU449 cells. HN1 was significantly overexpressed in HCC tumors compared to normal liver tissues. Silencing of HN1 significantly diminished the viability of HCC cells whereas overexpression of HN1 stimulated the viability of HCC cells. Silencing of HN1 increased apoptotic proteins and increased the number and size of colonies. In addition, silencing of HN1 inhibited the invasion and metastasis of HCC cells whereas overexpression of HN1 promoted the invasion and metastasis of HCC cells. In gene expression profiling, we identified 130 upregulated genes and 379 downregulated genes after HN1 silencing in HCC cells. Putative gene networks revealed suppressed expression of proteins associated with lipogenic signaling pathway. Silencing of HN1 significantly inhibited the expression levels of SREBP1 and SREBP2 of HCC cells whereas overexpression of HN1 increased the expression levels of SREBP1 and SREBP2 of HCC cells. In addition, silencing of SREBP1 also diminished the expression levels of HN1 and suppressed the survival and metastasis of HCC cells. In cholesterol assay and triglyceride assay, silencing of HN1 inhibited the lipid formation of HCC cells whereas overexpression of HN1 promoted the lipid formation of HCC cells. Taken together, HN1 encourages the proliferation, invasion and metastasis of HCC cells in part through the activation of SREBP signaling pathway. Therefore, our results suggest that targeting HN1 may constitute a potential therapeutic strategy for HCC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.