bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsaicin suppressed body weight gain and pain reaction in mice
Authors: Yang William , Xu Benjamin , Xu Richard , Ouyang Kevin , Ouyang Amy , Shan Huimin , Wang Hong
Published: November 2023

Capsaicin is a hot pepper extracts and has been reported as an anti‐inflammatory and anti‐oxidant agent. It was suggested that Capsaicin may potentially control peripheral nerve pain and has anti‐obesity effect. To test this hypothesis, we examined the effect of Capsacin on body weight gain, general metabolism and pain reaction in the C57BL/6J mice. Male mice at 6 weeks of age were fed with capsaicin (2 mg/kg body weight) or vehicle (0.9% saline, 3% ethanol and 10% Tween 80) every other day for a total of 90 days (n=10). The average weight of mice is about 18.1 grams at 6 weeks of age. The control mice fed with vehicle has a normal body weight gain and grown to 26.3 grams by the end of the experiments at 4.5 month of age. Capsacin fed mice reached 24.1 grams by the end of the experiments, a 12% suppression on body weight gain. Mouse metabolism was assessed in a metabolic cage for 24h and was found not altered by Capsaicin supplement. Finally, we tested mouse pain reaction on a 52–54°C hot plate (Ugo Basile, Varese, Italy) by using either jumping or hind‐paw licking as the nociceptive endpoint. We found that Capsaicin delayed the pain reaction. Hot plate pain reaction time was 7.5 seconds in the control mice and extended to 14.5 seconds in mice fed Capsaicin for 30 days. After 90 days of Capsaicin treatment, pain reaction remained latent as 12.9 seconds as compared with that 7.7 seconds in the control mice. We conclude that Capsaicin can control body weight gain and suppress peripheral nerve pain reaction in adult mice. Our study support the hypothesis that hot pepper is beneficial to prevent obesity and suppress pain reaction. Study is ongoing to take advantage of this common dietary ingredient to prevent the onset and progression of obesity in metabolic disease mice and to test its clinical relevance.

Support or Funding Information

This study was supported by research funding from NIHR01HL077288
How does Estrogen Influence Attention? Impact of 17‐beta Estradiol on Performance in an Attentional Set Shifting Task
Authors: Chen Sandi , Kolangara Shiva , Mokler David
Published: November 2023

Estrogens have been shown to affect learning and memory in female rats. ADHD is 3–9× more prevalent in males, suggesting that gonadal hormones may be in part responsible for the observed disparity between the sexes. In this disorder dopamine and norepinephrine levels in the ventromedial prefrontal cortex may be deficient, as evidenced by the use of stimulants to treat this disorder. Estrogen has been shown to inhibit dopamine reuptake in the prefrontal cortex this increasing extracellular levels of dopamine. Our previous work has suggested that in ovariectomized female rats, estradiol supplementation yielded higher levels of dopamine in the PFC than in male rats (1). The purpose of the present study was to evaluate the effect of estrogen in ovariectomized (OVX) female Long‐Evans rats in the attentional set‐shifting task (ASST)(2), a measure of attention which is strongly associated with monoamine levels in the vmPFC. Adult female rats were ovariectomized (OVX) or underwent a sham surgery. OVX rats were then randomized into two groups and given injections of 21 ug/kg 17‐B‐estradiol or vehicle every other day for the remainder of the study, while sham surgery animals were given vehicle injections. Rats were then tested in the ASST, wherein rats are trained to dig in pots for food reward. Pots are labeled with three dimensions, scent, digging material and texture of the pot and trained to dig for a food reward. Once the animal reaches criteria performance in a simple discrimination (SD) and then a complex discrimination (CD), the animal is then tested for performance in the intradimensional shift (ID), followed by a reversal (IDR). The animal is then exposed to an extradimensional shift (odor to digging material) (ED), followed by the reversal within this ED (EDR). This study found that OVX rats performed better in the ASST than sham or OVX + E animals, possibly reflecting a complicated dose‐response relationship to 17‐B‐estradiol administration. Further studies are underway to assess the levels of dopamine, norepinephrine, and serotonin in the ventromedial prefrontal cortex of these animals using in vivo microdialysis.

Support or Funding Information

SC supported by a Morgane Research Fellowship from UNECOM.
Systemic and Central Nervous System Levels of Neutrophil Gelatinase‐Associated Lipocalin after Cardiac Surgery Are Associated with Postoperative Cognitive Impairment
Authors: Schoemaker Regien G , Hovens Iris B
Published: November 2023

Introduction

Postoperative cognitive dysfunction (POCD) is a debilitating surgical complication, with cardiac surgery patients at particular risk. The systemic and central inflammatory response to surgery is considered to be a key factor in POCD development. Neutrophil gelatinase‐associated lipocalin (NGAL), a sensitive marker for inflammatory damage, has previously been associated with development of depressive symptoms in patients with cardiac disease. The current study aimed to investigate the association of systemic and central NGAL concentrations with postoperative cognitive performance in a rat‐model for POCD.

Methods

Male Wistar rats were subjected to ischemia reperfusion of the left coronary artery (cardiac surgery), received thoracic sham surgery or remained naïve. Cognitive performance was assessed in the second postoperative week. Two weeks following surgery plasma (ELISA) and brain (immunohistochemistry) NGAL levels were determined.

Results

NGAL was increased from 80±7 ng/ml in control rats to 321±48 ng/ml (p<0.01) and 278±53 ng/ml (p<0.01) in rats that had undergone thoracic sham surgery or cardiac surgery respectively (F2,33=9.4, p<0.01). NGAL in the paraventricular nucleus of the hypothalamus (PVN) was increased significantly after cardiac surgery only (F2,29=9.2, p<0.01; control: 13±1%; sham: 15±1%; cardiac: 18±1%, p<0.01). The route of anesthesia did not affect NGAL levels. Plasma NGAL concentrations in cardiac surgery and control rats were significantly correlated with performance in the novel location test (r=−0.46, p=0.04), and learning (r=0.50, p=0.30) and reversal learning (r=0.66, p=<0.01) in the Morris water maze, while PVN NGAL was correlated with novel location recognition only (r=−0.53, p<0.01).

Conclusions

Opening of the thorax appears to be associated with a marked long‐lasting rise in systemic NGAL concentrations, but only in cardiac surgery this is associated in increased NGAL in the brain, specifically in the PVN. These surgery‐specific alterations in NGAL may provide a lead towards understanding the cognitive sequelae of cardiac surgery
Baseline levels and baroreflex control of cardiac sympathetic nerve activity during renovascular hypertension
Authors: Ramchandra Rohit , George Bindu , Mahesh Darvina
Published: November 2023

Globally, hypertension affects one in three adults and the sympathetic nervous system has been implicated in the development of hypertension. In this context, increased sympathetic drive to the heart promotes arrhythmias and sudden death in patients, but the level of cardiac sympathetic nerve activity (CSNA) in hypertension has been assessed only by indirect methods. We tested the hypothesis that directly recorded CSNA is increased in renovascular hypertension. Renovascular hypertension was induced by clipping of one renal artery. Following three weeks post‐clip, resting levels of mean arterial pressure, heart rate CSNA and renal SNA (RSNA) were recorded in conscious ewes. Baroreflex control of heart rate and CNSA was assessed using intravenous infusions of phenylephrine and sodium nitroprusside. The same protocol was repeated in sham clip ewes (n=5). Renal clipping was associated with a significant increase in resting MAP (108±4 vs. 87±6 mmHg; n=10) and resting CSNA (38±3 vs. 30±2 bursts/min; n=5 and 7). In contrast, there was no difference in resting RSNA levels (67±11 vs. 70±8 bursts/min; n=4 and 3) between the groups. The sensitivity of baroreflex control of CSNA and RSNA was unchanged. This study provides the first direct evidence that CSNA is increased in a sheep model of renovascular hypertension. This increase in SNA was specific to the heart at this stage of hypertension since resting RSNA levels were unchanged. This study indicates an important role for CSNA in mediating the chronic elevation in MAP in renovascular hypertensive animals.

Support or Funding Information

Supported by The University of Auckland Faculty Research Development Fund and the Maurice and Phyllis Paykel Trust
Differences in Gastrocnemius mRNA Expression in Sedentary and Chronically Resistance Trained Rats Fed a Standard Chow Diet, or a Low‐Carbohydrate Diet, or a Western Diet
Authors: Hyatt Hayden W , Mobley C. Brooks , Kephart Wesley C , Holland A. Maleah , Mumford Petey , Lowery Ryan P , Roberts Michael D , Wilson Jacob M , Kavazis Andreas N
Published: November 2023

Low‐carbohydrate diets (LCD) can facilitate weight loss, but their effects on skeletal muscle remain equivocal. In this experiment we investigated the effects of three diets on skeletal muscle gene expression in sedentary and resistance exercised rats. Male Sprague‐Dawley rats (9–10 weeks of age, 300–325 g) were divided into three groups: fed a standard chow diet (SCD) (30 g/day, 3.1 kcal/g, 58.0% CHO, 18.0%, fat 24.0% protein); fed a LCD (17 g/day, 5.2 kcal/g, 20.2% protein, 10.3% CHO, 69.5% fat); or fed a Western diet (WD) (20 g/day, 4.5 kcal/g, 15.2% protein, 42.7% CHO, 42.0% fat), for 6 weeks. During these six weeks animals were either sedentary (SED) or voluntarily exercised using resistance‐loaded running wheels (EXE). At the end of the experimental protocol, the gastrocnemius muscle was harvested and used to compare the gene expression of key metabolic targets in the gastrocnemius. There was a significant interaction (p = 0.04) in carnitine palmitoyltransferase 1B (CPT1B) mRNA levels in the gastrocnemius. Specifically, SCD‐EXE showed a decline compared to SCD‐SED, whereas LCD‐EXE and WD‐EXE showed an increase compared to LCD‐SED and WD‐SED, respectively. Also, there was a trend (p = 0.05) for an interaction effect in peroxisome proliferator‐activated receptor gamma, coactivator 1‐alpha (PGC‐1α) mRNA and there was a trend (p = 0.08) for an activity effect in pyruvate dehydrogenase kinase, isozyme 4 (PDK4) mRNA in the gastrocnemius. There were no significant (p > 0.05) differences for phosphofructokinase (PFK), phosphoenolpyruvate carboxykinase (PEPCK), or glucose transporter type 4 (GLUT4) mRNA levels in the gastrocnemius. Our data indicate that the three diets tested affect the mRNA expression of metabolic genes in the gastrocnemius of sedentary and chronic resistance exercise rats. Future experiments should investigate if these changes translate to protein and/or activity level differences.

Support or Funding Information

Funding for this project was provided by JMW.
Voluntary Exercise Attenuates Reactive Oxygen Species Mediated Endothelial Dysfunction in Rodents Fed a High Sodium Diet Independent of Blood Pressure
Authors: Guers John J. , Kasecky‐Lardner Lauren , Farquhar William B. , Edwards David G. , Lennon‐Edwards Shannon
Published: November 2023

High sodium diets have been shown to cause endothelial dysfunction and diminish nitric oxide bioavailability independent of blood pressure (BP). This deleterious effect has been linked to increases in reactive oxygen species (ROS). Exercise is known for its beneficial effect on endothelial function. This may be due, in part, to a reduction in ROS production. The purpose of this study was to test the hypothesis that voluntary wheel running prevents the deleterious effect of high sodium on endothelial function by reducing ROS independent of BP. Eight week old male Sprague‐Dawley rats were placed on either a normal sodium (NS, 0.4%) or high sodium (HS, 4.0%) diet for 6 weeks. Diet groups were further subdivided into a sedentary (NS, HS) or exercise group (NS‐EX, HS‐EX), the latter were placed in a cage with 24‐hour access to a running wheel. BP was measured 3 times per week and did not change in any group. Blood and urine were collected at baseline and 6 weeks in order to assess serum and urinary sodium. Animals were sacrificed after 6 weeks and endothelium‐dependent relaxation (EDR) was assessed by dose response to acetylcholine (ACh), in the presence and absence of the superoxide scavenger tempol and the NADPH oxidase inhibitor apocynin (Apo) in femoral rings. Citrate synthase (CS) activity was measured in the soleus muscle. Serum and urinary sodium concentrations were elevated in HS groups relative to NS (p<0.05). CS activity was greater in both exercise groups indicating a training effect (p < 0.05). Femoral EDR was reduced in HS (n=11) compared to NS (n=10) rats as demonstrated by an attenuated maximal response (Emax: HS, 39.4% ± 4.8 vs. NS, 66.9% ± 3.9; p < 0.05). Emax was improved by tempol (HS+T, 65.9% ± 5.6; p <0.05) and Apo (HS+Apo, 62.9% ± 10.9; p <0.05) compared to HS alone. Total EDR as assessed by area under the curve (AUC) increased in HS animals with the addition of tempol but did not quite reach significance (AUC: HS, 63.8% ± 8.1 vs. HS+T, 89.6% ± 8.02; p=0.06). Exercise rescued Emax in the presence of a HS diet (HS‐EX (n=8), 76.8% ± 7.3 vs. HS, 39.4% ± 4.8; p<0.05) and AUC (AUC: HS‐EX, 127.1% ± 0.1 vs. HS, 63.8% ± 8.1; p <0.05). The addition of tempol and/or Apo had negative effects in general on EDR in the exercise groups. AUC was diminished in the HS‐EX group with the addition of tempol (p<0.05), while the administration of Apo decreased AUC in NS‐EX (n=10) (p < 0.05). Both tempol and apocynin decreased Emax significantly in NS‐EX animals. In conclusion, HS impairs EDR through NADPH oxidase meditated ROS. Voluntary wheel running restored EDR likely through a reduction in ROS. EDR was diminished in the exercising groups with the addition of antioxidants suggesting there may be a critical level of ROS needed for maintenance of normal vascular functioning.

Support or Funding Information

ACSM Foundation Research Grant
Effect of Post‐Exercise Ethanol on Signaling Pathways Regulating Mitochondrial Biogenesis
Authors: Engel Amy L. , Kanhere Arun P. , Jimenez R. Tomas , Coleman Denver J. , Blank Jason M
Published: November 2023

Ethanol is known to impair protein synthesis in muscle via inhibition of IGF‐1 signaling, but ethanol effects on pathways regulating mitochondrial biogenesis are not as clear. This study focuses on the combined effects of ethanol and exercise on mitochondrial biogenesis in skeletal muscle. Female rats (n=48) were randomly assigned to one of 4 groups: exercise followed by ethanol injection (RunEth), exercise with saline injection (RunSal), non‐exercise with ethanol injection (SitEth), or non‐exercise with saline injection (SitSal). Rats in the exercise groups completed interval running workouts to exhaustion on a treadmill (60 to 90 minutes duration). Immediately after exercise, rats were injected intraperitoneally with ethanol (75 mmols/kg) or an equivalent volume of saline. Three hours after the injection, hindlimb muscles were harvested and frozen in liquid nitrogen. Western blots were used to measure phosphorylation and/or abundance of proteins involved in regulating mitochondrial biogenesis (PGC‐1a, p‐p38 MAPK, p‐CREB) in samples from both soleus and plantaris. In plantaris of saline injected rats, acute exercise increased the abundance of PGC‐1a to 2.5 times the resting level (p=0.002), but the exercise‐induced increase was blocked by ethanol (p=0.89). p‐p38 MAPK levels in plantaris were not altered by running (p=0.16) or ethanol (p=0.81). Neither exercise nor ethanol altered PGC‐1a, p‐p38 MAPK, or p‐CREB in soleus 3 hours after exercise. Analysis of mRNA responses is ongoing.
CARDIOVASCULAR ALTERATIONS IN THE ACUTE PHASE OF CHAGAS DISEASE IN SEDENTARY AND TRAINED MICE
Authors: Martins‐Pinge Marli Cardoso , Lucchetti Bruno Fernando Cruz , de Ataides Raquel Hiviny , Zanluqui Nagela Ghabdan , Lovo‐Martins Maria Izabel , Tatakihara Vera Lucia , Michelini Lisete Compagno , Pinge‐Filho Phileno
Published: November 2023

Trypanosoma cruzi infection causes heart inflammation and fibrosis with changes in the architecture and functionality of the heart. The literature shows that physical activity (PA) of chronic moderate‐intensity acts as a factor of resistance against T. cruzi infection in animals. The parameters of mean arterial pressure, heart rate (HR) and nitric oxide (NO) accompanying the acute phase of infection in animals trained have not been clarified. We aimed to evaluate the cardiovascular parameters, production of NO in the heart and plasma, parasitaemia and mortality in trained mice infected with T. cruzi. This study was approved by our institutional ethic committee (process number: 28105.2014.72). The AF was performed on treadmill for nine weeks. Then, the mice were infected with 5×103 trypomastigotes of T. cruzi (Y strain) or PBS (control). On days 7, 14 and 20 after inoculation (dpi) cardiovascular parameters were evaluated by CODA platform. The parasitemia was performed using the method of Brenner and dosage of NO by the Griess method. Data were analyzed using analysis of variance two‐way ANOVA. We observed resting bradycardia (758bpm vs 703bpm) and a better performance in the performance test (2.2 vs 1.5 km / h) in trained animals (n = 27) compared with sedentary (n = 14). With 20 dpi we found a decrease in HR in infected sedentary animals (SI) (n = 10) compared to the infected trained (TI) (n = 10) (669 vs 765bpm, p<0.05). We observed a decreased production of NO in cardiac tissue in IT compared with IS (6,51 vs 20.73 NO2μM). We observed a decrease in parasitemia in IT compared to IS in the 15 dpi (2,03×106 vs 1,17×106 parasites / ml) and 17 dpi (3,37×106 vs 1,02×106 parasites / ml). IT animals showed increased survival compared to SI. Exercise training improves cardiovascular parameters during infection by T. cruzi, contributing to the increased survival of infected animals, and NO may participate in this process.

Support or Funding Information

CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)
Effects of Ovarian Hormone Loss and Aerobic Fitness on Brown Adipose Tissue Immunometabolic Characteristics in Rats
Authors: Vieira‐Potter Victoria Jeanne , Park Young‐Min , Zidon Terese M. , Welly Rebecca J.
Published: November 2023

Ovary‐intact female rodents are less susceptible to white adipose tissue (WAT) inflammation and insulin resistance (IR). Females also are known to have greater brown adipose tissue (BAT) activity and uncoupling protein (UCP)‐1 expression. Ovary removal (i.e., OVX) increases adiposity, WAT inflammation, and IR. We recently demonstrated that female rats selectively bred for high running capacity (i.e., high‐fit HCR), compared to those bred for low running capacity (i.e., low‐fit LCR), are protected against OVX‐associated weight gain and IR and have more BAT, which correlates strongly with their greater resting energy expenditure. The objectives of the present study were to determine: 1) how HCR and LCR rats differ in their interscapular BAT immunometabolic characteristics; and 2) how OVX affects BAT of HCR and LCR rats. HCR and LCR rats had OVX or SHM (i.e., sham ovariectomy) surgeries at 25 weeks of age and were followed for up to 27 weeks, during which time they remained sedentary and were fed standard rodent chow. Food intake, weight gain, adiposity (DXA and fat pad weights), circulating adipokines (ELISA), spontaneous cage physical activity (SPA) (metabolic cages with beam break quantification) and insulin sensitivity (hyperinsulinemic euglycemic clamps) were compared among the 4 groups via 2‐way ANOVA to determine main effects of line (i.e., HCR v. LCR), treatment (i.e., OVX v. SHM), and line × treatment interactions (which were followed by LSD multiple comparison tests, as appropriate); correlations are Pearson bivariate. Statistical analyses were performed using SPSS v21 and P<0.05 was considered significant. BAT was assessed via UCP‐1 immunostaining, gene (rtPCR) and protein (Western) expression, citrate synthase activity (enzyme assay), and insulin‐mediated glucose uptake under clamp conditions. While HCR and LCR rats did not differ in histological, gene, enzymatic, or protein indexes of non‐stimulated BAT activity, HCR had lower BAT inflammatory cytokine (e.g., TNF‐a) and T cell (e.g., CD3, CD4) gene expression (all P<0.05 compared to LCR) and markedly greater insulin‐stimulated glucose uptake into BAT (P<0.01 compared to LCR), which was strongly related to their improved systemic glucose infusion rate (r = 0.5, P=0.014). In both HCR and LCR rats, OVX reduced skeletal muscle insulin sensitivity (P<0.02) but did not affect insulin‐stimulated glucose uptake into WAT or BAT. Unexpectedly, in HCR and LCR rats, OVX increased BAT UCP‐1 and reduced several inflammatory genes (e.g., TNF‐a, CD3, CD4, CD8, all P<0.05). We hypothesize that UCP‐1 up‐regulation following OVX may be a compensatory defense mechanism against oxidative stress resulting from OVX.

Support or Funding Information

MU Research Council Grant to VJ Vieira‐Potter
The Role of Body Habitus in Predicting Cardiorespiratory Fitness: Findings from the FRIEND Registry
Authors: Baynard Tracy , Arena Ross A , Myers Jonathon , Kaminsky Leonard A
Published: November 2023

Body habitus has been previously reported to be important in the development of non‐exercise prediction models for estimating cardiorespiratory fitness (CRF). Yet, these previous models have included indices of physical activity, which is not widely assessed in the clinical setting.

Purpose

To validate and cross‐validate a non‐exercise prediction model from a large and apparently healthy U.S. cohort of individuals who underwent an analysis of body habitus (waist circumference (WC) and body mass index (BMI)) with measured CRF.

Methods

The large cohort (5030 individuals) was split into validation (4030) and cross‐validation groups (1000), whereby waist circumference and maximal aerobic capacity (VO2max) were assessed by rigorously approved laboratories.

Results

VO2max was estimated in 2 multiple regression equations using age, sex, and either WC (r = 0.77; standard error of the estimate (SEE) 6.70 mLO2 ·kg−1·min−1) or BMI (r = 0.76; SEE 6.89 mLO2 ·kg−1·min−1). Cross‐validation yielded similar results. However, as VO2max increased, there was increased bias, suggesting VO2max may be underestimated at higher values.

Conclusions

Both WC and BMI prediction models yielded similar findings, with WC having a slightly smaller SEE. These measures of body habitus appear to be adequate in predicting CRF using non‐exercise parameters, even without a measure of physical activity. Caution should be taken when using these equations in higher fit individuals.

Support or Funding Information

TKC Global Solutions, LLC.
Exercise Limits Loss of Respiratory Function Seen with Doxorubicin Treatment without Affecting Muscle Function
Authors: Louw Makensie J. , Crandall Amy D. , Murphy Tyler S. , Reynolds Merrick S. , Bernhisel Drew , Hancock Chad R.
Published: November 2023

Doxorubicin (DOX) is a commonly‐used chemotherapeutic drug with side effects including skeletal muscle wasting and weakness. It has been shown that DOX contributes to skeletal muscle damage through increasing oxidative stress. It is hypothesized that DOX interacts with free cellular iron to catalyze to the formation of reactive oxygen species (ROS). ROS contribute to cell damage and dysfunction, and thus may play a part in the skeletal muscle wasting seen with DOX treatment. Recent work has shown that exercise may help protect against this oxidative environment, thus preventing skeletal muscle wasting. We hypothesized that exercise would limit the loss of muscle function and respiration seen with DOX treatment. Male C57BL/6 mice were randomly placed into three groups: control, DOX, or EX+DOX. Control mice received five doses of saline orally for five days before sacrifice, and one dose of saline intraperitoneally three days before sacrifice. DOX mice received one dose of DOX at 15 mg/kg three days before sacrifice. EX+DOX mice were run for 60 min at ~20 m/sec for five consecutive days, then allowed to rest for two days. Mice then received a 15 mg/kg dose of DOX three days before sacrifice. Muscle function of the gastrocnemius platantaris soleus complex was measured in situ with mice under anesthesia (100 msec tetanic contractions at 0.5 Hz for 6 minutes). Mitochondrial respiratory function was measured in permeabilized fiber bundles from red gastrocnemius using high‐resolution respirometry (OROBOROS Oxygraph‐2k). Treatment with DOX, with or without exercise, resulted in a 17.2% – 20.2% decrease in overall body weight compared to control (p‐value < 0.001). Interestingly, the weight difference between DOX and EX+DOX groups was not significant. Additionally, DOX treatment reduced respiratory capacity compared to control for complex I‐stimulated, complex II‐stimulated, and uncoupled (maximal) respiration (21.6% – 57.1% reduction from control levels, p‐value < 0.001). EX+DOX limited the loss of respiratory function seen with DOX alone (i.e., uncoupled respiration was 78.4% of control, p‐value = 0.15). Surprisingly, there were no significant differences in peak specific tension, twitch tension, half relaxation time, or muscle fatigue between any of the groups. Our findings indicate that while exercise may prevent loss in respiratory function in skeletal muscle, this may not result in differences in muscle function. More research is needed in this area to find treatment options for DOX‐induced skeletal muscle dysfunction.
The Effect of Endurance Exercise on Doxorubicin Cardiotoxicity and Antitumor Efficacy in Tumor‐Bearing Mice
Authors: Lien Chia‐Ying , Jensen Brock Thomas , Chen Mei‐Li , Wu Chung‐Hsin , Lin Ching‐Lung , Chuang Tai‐Yuan
Published: November 2023

Doxorubicin (DOX) is a highly effective antineoplastic agent used in the treatment of various cancers. Conversely, DOX treatment can result in acute and chronic cardiotoxicity and may eventually lead to congestive heart failure and premature death. Many studies have reported that endurance exercise attenuates both acute and chronic DOX cardiotoxicity. However, the majority of studies used non‐tumor‐bearing animals. Therefore, it is of great interest to investigate the combined effects of exercise and DOX on the anti‐tumor efficacy of this commonly used chemotherapy.

Purpose

The primary purpose of this study was to determine if endurance exercise can attenuate DOX cardiotoxicity and preserve the antineoplastic activities of DOX. Secondarily, if the antineoplastic efficacy was maintained with endurance exercise and DOX treatment, what mechanisms are responsible for cardioprotection.

Methods

Six week old C57BL/6 mice were randomly assigned into one of following groups: Control (n=6), Tumor_SED_DOX (n=9), Tumor_ED_DOX (n=9), Tumor_EA_DOX (n=9). Excluding the control group, all animals were inoculated with melanoma cells (B16F10, 5 × 106) at 6 weeks of age and received an injection of DOX (6 mg/kg) at 8 weeks. Two days post inoculation, Tumor_ED_DOX started an endurance exercise protocol. Two days post DOX injections, Tumor_EA_DOX started an endurance exercise protocol. Control and Tumor_SED_DOX were limited to normal cage activity. Following exercise and DOX treatments, cardiac function was measured in vivo. Biochemical analyses were performed to determine inflammatory, apoptosis, and antioxidant responses to combined treatment.

Results

Tumor size was not significantly different across groups (Tumor_SED_DOX, 865±207 mm3; Tumor_ED_DOX, 692±133 mm3; Tumor_EA_DOX, 621±148 mm3, P > 0.05). Fractional shortening and ejection fraction was significant lower in control mice compared to all experimental groups (P < 0.05). Additional functional measures were not significant across all groups (P > 0.05). Biochemical analyses revealed Tumor_SED_DOX had greater inflammatory (NF‐kB) and apoptosis (AkT, Bax / Bcl‐2, cyt‐c) responses and reduced antioxidant expression (SOD2) (P < 0.05).

Conclusions

In this investigation, tumor size was unadulterated by combined exercise and DOX treatment. Cardiac dysfunction was not observed in DOX treated animals. Specifically, control animals FS and EF were not different from DOX treated animals. This was likely due to a inadequate cumulative dose of DOX (250 mg/kg). Interestingly, Tumor_SED_DOX still demonstrated exacerbated inflammation, apoptosis and impaired antioxidant defense when compared to exercise trained animals. This suggests that endurance exercise may still have protective effects against DOX‐induced cardiotoxicity in a tumor bearing‐model.

Support or Funding Information

Ministry of Science and Technology of Taiwan: under Grant 104‐2410‐H‐002 ‐182 –
Individual Differences in Components of the Pressor Responses to Isometric and Dynamic Handgrip Exercise in Humans
Authors: Watanabe Kazuhito , Ichinose Masashi , Tsuji Bun , Maeda Seiji , Nishiyasu Takeshi
Published: November 2023

The aim of this study was to test the hypotheses that, in humans, cardiac output (CO) and total peripheral vascular resistance (TPR) responses to dynamic handgrip exercise vary among individuals as demonstrated recently with isometric handgrip exercise, and that the responses of the components mediating the pressor response have a similarity between those exercises in the same individuals. We studied 30 healthy male and female volunteers with a mean age of 25 ± 0.5 yr, body weight of 64 ± 2.4 kg, and height of 169 ± 1.5 cm (means ± SE). The subjects assumed a supine position and performed isometric and dynamic (30 contractions/min) handgrip exercise at 50% of maximal voluntary contraction until fatigue separately (84 ± 3 s and 178 ± 14 s, respectively). We assessed the magnitude of the variance in the individual changes in mean arterial pressure (MAP), CO and TPR at 20%, 40%, 60%, 80% and 100% of fatigue using inter individual coefficient of variation (CV). Although CVs for changes in CO and TPR between the rest and the exercise periods were not much different from the CV for change in MAP at 20% of fatigue, the CVs for changes in CO and TPR were 2‐ to 3‐fold greater than the CV for change in MAP at ≥40% of fatigue in both trials. Thus the components of the pressor responses to isometric as well as dynamic handgrip exercise varied widely among subjects at ≥40% of fatigue. In addition, the CO and TPR responses during dynamic handgrip exercise correlated positively with the corresponding responses during isometric handgrip exercise from 20% to 100% of fatigue (CO: r = 0.675–0.755, P < 0.01; TPR: r = 0.566–0.788, P < 0.01). Our findings demonstrate that the CO and TPR responses during moderate to exhaustive handgrip exercise (≥40% of fatigue) vary considerably among individuals compared to the pressor response irrespective of the exercise modality (isometric or dynamic). They also suggest that the CO and TPR responses to handgrip exercise is similar between the modalities in the same individuals throughout the course of exercise.

Support or Funding Information

This study was supported by the grants from Japan Society for the Promotion of Science.
Blocking Proteinase‐Activated Receptor‐2 Attenuates Amplified Pressor Response in Rats with Femoral Artery Occlusion
Authors: Lu Jian , Xing Jihong , Li Jianhua
Published: November 2023

A rat model of femoral artery ligation was employed to study the exercise pressor reflex in peripheral artery disease (PAD). Our prior studies have shown a functional interaction in proteinase‐activated receptor‐2 (PAR2) and transient receptor potential channel A1 (TRPA1) in muscle sensory nerves and TRPA1 is engaged in the amplified sympathetic responsiveness observed in rats with femoral artery occlusion. The current study was to determine the role played by PAR2 in regulating amplified blood pressure response observed in rats following 72 hours of femoral artery occlusion. Dorsal root ganglion (DRG) tissues of control limbs and limbs with 72 hours of femoral occlusion were obtained to examine the protein levels of PAR2 using western blot analysis. Femoral occlusion significantly increased expression of PAR2 in DRG (optical density: 1.02±0.03 in control vs. 1.57±0.05 after occlusion, P<0.05; n = 5 in each group). In addition, we examined the pressor response to static muscle contraction after 2, 10 and 20μg/kg of FSLLRY‐NH2 (a PAR2 inhibitor) were injected into the arterial blood supply of the hindlimb muscle of control rats and occluded rats. We found that FSLLRY‐NH2 failed to attenuate the pressor response to contraction in control rats. However, 10 and 20μg/kg of FSLLRY‐NH2 significantly attenuated the pressor response to contraction in occluded rats. i.e., in control rats the peak response of mean arterial pressure (MAP) was 26±5 mmHg after saline (n=6) and 24±3 mmHg after 20μg/kg of FSLLRY‐NH2 (n=6; P > 0.05 vs. saline); in occluded rats the peak response of MAP was 35±6 mmHg after saline (n=5) and 21±4 mmHg after 20μg/kg of FSLLRY‐NH2 (n=6; P < 0.05 vs. saline). Note that there was no difference in developed muscle tension between saline and FSLLRY‐NH2 groups (555±10 vs. 550±15 g in control rats, P > 0.05; and 556±10g vs. 571±20g in occluded rats, P > 0.05). Overall, our data suggest that PAR2 in muscle sensory nerves likely contributes to the amplified sympathetic and pressor responsiveness observed in experimental PAD rats.

Support or Funding Information

NIH P01 HL096570 and AHA Established Investigator Award 0840130N
Comparison of Food Availability in School Stores in Seoul, South Korea Before and After Implementation of Two National Food‐ and Nutrient‐Based Policies
Authors: Choi Seul Ki , Frongillo Edward A , Blake Christine E , Thrasher James F
Published: November 2023

Public health interest in preventing childhood obesity and chronic diseases by improving school food environments has been growing around the world. As part of this movement, the South Korean government implemented two policies restricting unhealthy food sales in school stores: 1) a food‐based policy enacted in 2007 restricts specific food sales (e.g., soft drinks), and 2) a nutrient‐based policy enacted in 2009 restricts energy‐dense, nutrient‐poor (EDNP) food sales in school stores. The purpose of the study was to assess the effects of the two policies on the school store food environment.

Foods sold in stores located in middle and high schools in Seoul, South Korea were observed before (2006, 15 stores) and after (2013, 12 stores) implementation of the two school store policies. After controlling for the total number of food types offered in school stores and school characteristics (school level, private/public, students’ sex, and income level), numbers and percentages of food types in each category were compared between 2006 and 2013. Also, number and percentage of EDNP foods in 2013 were examined using mixed models with school districts as random effects. All statistical analyses were conducted using SAS 9.4 (SAS Institute, Inc., Cary, NC).

The mean number of food types offered in school stores was significantly higher in 2013 (102.3 items) than in 2006 (41.1 items; p<0.001), even after adjusting for school characteristics (p=0.022). When controlling for the total number of food types and school characteristics, the mean number of soft drinks offered in a school store in 2013 (0.3 items) was significantly lower than in 2006 (1.9 items, p=0.032). Soft drinks, the target of the 2007 policy, were still available in 50% of school stores observed in 2013, while 60% of school stores observed in 2006 offered soft drinks. In contrast, EDNP foods, the target of the 2009 policy, were available in all school stores observed in 2013, and represented about 7.6% of food types offered.

In school stores in South Korea, a food‐based policy that prohibits soft drinks appears to have been more effective for decreasing availability of restricted items than a nutrient‐based policy. Neither of the two policies, however, eliminated access to unhealthy foods in school stores. To improve school store food environments, alternative strategies such as requiring healthy food sales are likely needed.

Support or Funding Information

This study was supported by the Walker Institute of International and Area Studies, University of South Carolina.
Cutaneous Vascular and Sweating Responses to Intradermal Administration of Prostaglandin E1 and E2 in Young and Older Adults: a Role for Nitric Oxide?
Authors: Fujii Naoto , Singh Maya Sarah , Halili Lyra , Boulay Pierre , Sigal Ronald J , Kenny Glen P
Published: November 2023

Cyclooxygenase (COX) contributes to cutaneous vasodilation and sweating responses, however the mechanisms underpinning these responses remain unknown. We hypothesized that prostaglandin E1 (PGE1) and E2 (PGE2), which are COX‐derived products, directly mediate cutaneous vasodilation and sweating through nitric oxide synthase (NOS)‐dependent mechanisms in young adults. Furthermore, we hypothesized that this response is diminished in older adults, since ageing attenuates COX‐dependent cutaneous vasodilation and sweating. In 9 young (4 males and 5 females, 22 ± 5 years) and 10 older (3 males and 7 females, 61 ± 4 years) adults, cutaneous vascular conductance (CVC, laser‐Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were measured at four intradermal forearm skin sites receiving incremental doses (0.05, 0.5, 5, 50, 500 μM each for 25 min) of PGE1 or PGE2 with and without co‐administration of 10 mM L‐NNA, a non‐specific NOS inhibitor. L‐NNA attenuated PGE1‐mediated increases in CVC in young adults, while it attenuated PGE2‐mediated increases in CVC in older adults (all P < 0.05). However, the magnitude of the PGE1‐ and PGE2‐mediated increases in CVC did not differ between groups (all P > 0.05). Neither PGE1 nor PGE2 increased sweat rate at any of the administered concentrations for either the young or older adults (all P > 0.05). We show that the cutaneous vasodilator response is mediated through NOS‐dependent mechanisms albeit via PGE1 in young adults and PGE2 in older adults, respectively. We also show that cutaneous vascular responsiveness to PGE1 and PGE2 is similar between young and older adults. Lastly, in both young and older adults, we show that both PGE1 and PGE2 do not directly increase sweat rate.

Support or Funding Information

This study was supported by the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014), and by Canada Foundation for Innovation (Leaders Opportunity Fund, 22529) (funds held by Dr. Glen P. Kenny).
Ablation of eNOS Does Not Promote Adipose Tissue Inflammation
Authors: Jurrissen Thomas J , Sheldon Ryan D , Gastecki Michelle L , Zidon Terese M , Rector R. Scott , Vieira‐Potter Victoria J , Padilla Jaume
Published: November 2023

Adipose tissue (AT) inflammation is a hallmark characteristic of obesity and an important determinant of insulin resistance and cardiovascular disease; therefore, a better understanding of factors regulating AT inflammation is critical. It is well established that reduced vascular endothelial nitric oxide (NO) bioavailability promotes arterial inflammation; however, the role of NO in modulating inflammation in AT remains disputed. In the present study, ten‐week old C57BL6 wild‐type and eNOS knockout male mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat, 17% sucrose, and 1% cholesterol) for 18 weeks (n=7–8/group). In wild‐type mice, Western diet‐induced obesity led to increased visceral white AT expression of inflammatory genes (e.g., MCP1, TNFα, CCL5 mRNAs) and markers of macrophage infiltration (e.g., CD68, ITGAM, EMR1, CD11C mRNAs and Mac‐2 protein), as well as reduced markers of mitochondrial content (e.g., oxphos complex I and IV protein). These effects of Western diet on visceral white AT were not accompanied by decreases in eNOS activation. eNOS knockout mice, independent of the diet, were leaner and did not exhibit greater white or brown AT inflammation compared to wild‐type mice. Collectively, these findings do not support the hypothesis that reduced NO signaling contributes to obesity‐related AT inflammation.

Support or Funding Information

This work was supported by a University of Missouri Life Sciences Fellowship (R. D. Sheldon), Veterans Health Administration grant CDA2 BX001299 (R. S. Rector), and National Institute of Health grants K01 HL‐125503 and R21 DK‐105368 (J. Padilla).
Adipose Inflammation and Cardiovascular Disease Risk Factors in Obesity‐Prone Osborne‐Mendel and Obesity‐Resistant S5B/Pl Rats
Authors: Primeaux Stefany , Souza‐Smith Flavia , Poret Jonquil , Mouton Alan , Marcell Shawn , Battle Claire , Braymer H. Douglas , Harrison‐Bernard Lisa
Published: November 2023

Obesity‐related increases in visceral adipose deposition and inflammation, circulating triglyceride (TRG), LDL cholesterol, and C‐reactive protein (CRP) enhance the risk for CVD. These effects may be intensified by the consumption of an energy dense, high fat diet (HFD). The current study tested the hypothesis that HFD consumption would exacerbate CVD risk factors in obesity‐prone Osborne‐Mendel (OM) rats, compared to obesity‐resistant S5B/Pl (S5B) rats. OM and S5B rats were fed either a HFD (60% fat; n=6/strain) or low fat diet (LFD, 10% fat; n=6/strain) for 7 weeks. A multiplex rat cytokine/chemokine panel was used to assess the expression of inflammatory markers in epididymal fat and subcutaneous fat depots. Circulating TNF‐α and CRP levels were determined by ELISA and circulating TRG, HDL, LDL and total cholesterol were assessed. Cardiac hypertrophy was assessed by total heart and left ventricular mass. As expected, body weight, % visceral adiposity (OM‐HFD 5.3% vs. S5B‐HFD 1.2%) and adipocyte size were increased by HFD intake to a greater extent in the obesity‐prone OM rats. Higher basal levels of IL‐6, TNF‐α, IL‐1α, and IL‐1β were detected in the epididymal fat depots of obesity‐prone rats. Consumption of a HFD increased Il‐6, TNF‐α, IL‐1α, and IL‐1β in the epididymal fat of both OM and S5B rats. HFD intake synergistically increased TNF‐α expression in OM rats (2‐fold vs. S5B‐HFD; p<.05). However, circulating levels of TNF‐α were decreased in OM rats fed the HFD. In subcutaneous fat, HFD intake did not alter inflammatory marker expression in either OM or S5B rats, though basal expression of IL‐6, IL‐1α, and IL‐1β was higher in subcutaneous fat of OM rats, compared to S5B rats (p<.05). Circulating TRG was increased and HDL cholesterol was decreased in OM rats, regardless of diet. Circulating CRP levels were increased by HFD in both strains, suggesting an inflammatory response to the HFD (p<.05). Left ventricle/heart ratio was lower in OM rats, but increased with HFD consumption in this strain, suggesting cardiac hypertrophy. A HFD‐induced increase in pro‐inflammatory cytokine expression in the visceral adipose depot, but not in subcutaneous fat, supports the role of visceral fat in the deleterious effects of dietary fat. Higher basal levels of pro‐inflammatory cytokines in adipose tissue and TRG and lower levels of HDL cholesterol in obesity‐prone rats suggest that this strain is at a greater risk for developing CVD compared to the obesity‐resistant rats.

Support or Funding Information

COBRE 1P30GM106392
Predicting Metabolic Syndrome Risk Factors Using Different Anthropometric Indices Of Obesity In A Farm Worker Population, Western Cape South Africa
Authors: Nell Theo A , Kruger Maritza J
Published: November 2023

Anthropometric assessments can be used in epidemiological field studies to assess health status. The prevalence of both the metabolic syndrome(MetS) and obesity are on the increase in the South African population, thus increasing the risk of developing lifestyle related diseases including diabetes, cardiovascular disease, and cancer. The farm worker population in the Western Cape Province are also now included in this increased prevalence. Using anthropometrical indices, such as body mass index (BMI), waist circumference (WC), and waist to hip ratio (W:H) in epidemiological field studies, could possibly increase the risk prediction of the metabolic syndrome as well as obesity.

This cross‐sectional study included both men and women (total n= 188; n= 147 women and n=41 men) which revealed a total metabolic syndrome prevalence of 42.6%. The women in this sample had a 46% prevalence compared to the men (29%). We then wanted to distinguish the association between anthropometrical indices and the metabolic syndrome risk factors for both genders, irrespective of their metabolic status.

We reported that the women showed significant correlations for all the metabolic syndrome risk factors with the following anthropometrical indices; BMI, WC and W:H. This was not seen for the men where BMI, WC and W:H only significantly correlated with high density lipoprotein cholesterol(HDL‐c), glucose (Gluc), triglycerides (TG), and diastolic blood pressure (DBP). Since the women seemed to have a higher risk for the metabolic syndrome we further subdivided only the women into either the metabolic syndrome (IDF criteria) versus non‐metabolic syndrome groups.

In the metabolic syndrome group, W:H was only significantly correlated with TG (r=0.32; p=0.007) and Gluc (r=0.39;p=0.001), whilst, BMI was significantly correlated with systolic blood pressure(SBP) (r=0.39; p=0.001) and DBP (r=0.31; p=0.001). Waist circumference was only significantly correlated with SBP (r=0.35; p=0.003).

For the non‐metabolic syndrome group, only W:H significantly correlated with TG (r=0.43; p=0.000).

The BMI, WC and W:H may be better predictors of the metabolic syndrome in the female group, however, when this group were subdivided this was no longer evident. Here, the W:H and BMI indices were better predictors of only certain risk factors.

Support or Funding Information

This study was funded by the Cancer Association of South Africa (CANSA)
Soybean Oil High Fat Diet Reduces Hypothalamic Oxytocin Immunoreactivity
Authors: Ho Catherine , Deol P. , Richardson H. , Platt D. , Yang E. , Jiang T. , Sladek F. M. , Curras‐Collazo M.
Published: November 2023

It is well established that the intake of fatty foods induces obesity, although relatively little attention is given to the type of fat. Male mice fed a high fat diet (HFD) rich in saturated fat had significantly less weight gain, adiposity, glucose intolerance and fatty liver as compared to mice fed a high fat diet containing soybean oil (SO), rich in the polyunsaturated omega‐6 fatty acid linoleic acid (LA‐HFD) or a diet rich in a genetically modified, low LA soybean oil (PL‐HFD). Both LA‐HFD and PL‐HFD also have similarly higher levels of the phytosterol, stigmasterol, than HFD. The adverse effects of SO may be mediated, in part, by brain oxytocin, although this has not been studied. Oxytocin is anorexigenic and mouse models of obesity show reduced brain Oxt. Here we examined the effect of SO diet on oxytocin. Male C57BL/6N mice were fed for 17–27 weeks either vivarium chow (VC) or one of 4 iso‐caloric diets: HFD (coconut oil), LA‐HFD (SO), PL‐HFD (GM SO) or Stigma‐HFD (coconut oil with same amount of stigmasterol as LA‐ and PL‐HFD) or control (VC). Immunoreactivity (IR) to an antibody specific for oxytocin‐neurophysin in the paraventricular nucleus of the hypothalamus was markedly lower in LA‐, PL‐ and Stigma‐HFD groups relative to HFD and VC. Similar but less marked differences were obtained in arcuate nucleus. For the supraoptic nucleus a similar pattern was observed except that oxytocin IR in PL‐HFD was not reduced (n=5–6 experiments, 3–5 animals per group). Our findings demonstrate that the stigmasterol can decrease paraventricular oxytocin and this may help explain the obesity and diabetic propensity associated with a diet rich in SO.

Support or Funding Information

Support: APS fellowships (C.H., D.P.), UCR UGR Student Mini‐Grant (C.H), NIEHS T32 fellowship (P.D.) and Collaborative grant, UCR ORED (F.S., T.J. and M.C.C.).