bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated sympathoadrenal response following active ascent to 3,600m is not associated with acute mountain sickness
Authors: Berkemeier Quint , Figueiredo Peter , Landspurg Steven , Staab Janet , Karl James , Femling Jon , Williams Jason
Published: May 2024

Previous reports have suggested an increase in plasma epinephrine (EPI) and either an increase, no change or decrease in norepinephrine (NE) following acute (< 4 h) exposure to high altitude (HA). In addition, previous research has demonstrated an exercise-induced increase in EPI and NE during exercise initiated following arrival at HA. Last, some but not others have reported an association between increased sympathoadrenal activity and acute mountain sickness (AMS). We hypothesized that elevated sympathoadrenal activity induced from active ascent on foot to 3,600m may contribute to the development of AMS. Thirty-seven Soldiers (mean ± SD; 6 women; age=25.5±4.9 years) were tested at their baseline residence (BLR; Fort Bliss, TX, 1,190m), transported to Taos, NM (2,845m), then hiked (n=18) or were driven (n=19) to the HA data collection site where they resided for four days (68hrs). AMS Cerebral Factor Score (AMS-C) was determined using the Environmental Symptoms Questionnaire (ESQ-III) recorded twice at HA on day 1 (HA1), five times on days 2 (HA2) and 3 (HA3) and once on day 4 (HA4). If AMS-C was ≥0.7 on any measurement occasion, individuals were categorized as AMS-susceptible (AMS+, n=11) others were AMS-resistant (AMS─, n=26). Plasma EPI (pg/ml) and NE (pg/ml) were measured from venous blood draws at 06:00 at BLR, a non-fasted blood draw at 18:00 following ascent on HA1, and subsequent fasted blood samples at 06:00 on each morning at HA (HA2, HA3, HA4). AMS-susceptibility was not associated with the EPI or NE response in any condition so both cohorts were combined. The EPI response to active vs. passive ascent was similar with an increase (p<0.05) from BLR (28.0±26.8) to HA1 (47.5±40.3) followed by a subsequent decrease (p<0.05) from HA1 to HA2 (28.0±18.6) through HA4 (25.4±16.9). NE, however, increased (p<0.05) only in the active ascent group from BLR (413±216) to HA1 (729±281) and remained stable from HA1 through HA4 (644±192). The passive ascent group demonstrated no change in NE from BLR (327±126) to HA1 (413±181) through HA4 (466±144). NE levels were similar (p>0.05) in the active vs passive ascent group at BLR but higher (p<0.05) in the active ascenders on HA1 through HA4. In conclusion, contrary to our hypothesis, the sympathoadrenal response to HA was not impacted by AMS susceptibility but active ascent induced a greater NE response following ascent and throughout the duration of the HA stay.

USAMRDC. Authors’ views not offcial U.S. Army or DoD policy.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Acute Exposure to High-Altitude Results in Changes to Immune Cell Populations
Authors: Vargas Abel , Mkrtchyan Karapet , Penuelas Veronica , Pham Kathy , Frost Shyleen , Moya Esteban , Yu James J
Published: May 2024

High altitude is a challenging environment due to the reduced atmospheric pressure and oxygen availability, increased ultraviolet radiation, and reduced temperature relative to sea level. Previous studies in individuals who travel to high altitude demonstrate differential expression of genes involved in inflammation and innate immune system activation. This study aims to extend these findings by defining changes in immune cell population distributions and cell phenotypes during travel to high altitude. We hypothesized that acute high-altitude exposure would lead to shifts in immune cell populations toward a pro-inflammatory phenotype due to cellular stress caused by hypoxemia and tissue hypoxia. Participants (N=17) traveled to Barcroft Station in the White Mountain Research Center (3800 m). Whole blood was collected during fasting at sea level on the morning of ascent and each morning at high altitude for three days. Cells in whole blood were fixed and stained within 1-2 hours of collection and were processed via flow cytometry upon return to sea level. We observed a decrease in classical monocytes on the first (p=0.010) and second (p=0.003) mornings of high-altitude acclimatization to sea-level baseline, and an increase in intermediate monocytes on the first (p=0.013) and second (p=0.014) mornings at high altitude. We also observed an increase in B cells on the second (p=0.004) and third (p=0.004) mornings at high altitude compared to sea-level baseline (mean: 3.53%, SD: ±1.82). These results indicate that acute high altitude exposure results in a shift toward a pro-inflammatory monocyte phenotype and supports prior research suggesting a significant role of hypoxia in modulating B cell function.

This research was supported through funding provided by a private donor.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Differences in lactate metabolism between middle- and long-distance runners
Authors: Inaba Takeru , Watanabe Takuya , Morita Yuki , Hatta Hideo
Published: May 2024

It is important for runners and coaches to figure out the characteristics of lactate metabolism in terms of planning the proper training. This study investigated the differences in lactate production and oxidation capacities between middle- and long-distance runners by using blood lactate concentration. We hypothesized that long-distance runners have greater capacity to oxidize lactate and middle-distance runners have greater capacity to produce lactate. In this study, 14 middle- and 14 long-distance male runners performed a multi-stage incremental test until exhaustion. Each running stage was 3-minute with 1-minute rest between stages. Blood lactate concentration was measured at rest and after each stage, and some metrics associated with runner’s capacity to oxidative lactate during moderate intensity exercise were calculated. The changes in blood lactate concentration measured after the final state of the test were modeled as a biexponential time function to evaluate lactate productive and oxidative capacities after high-intensity exercise. During moderate-intensity exercise, long-distance runners showed significant decrease in blood lactate concentrations during the first few stages of the test compared to rest, indicating greater oxidation of lactate than production of lactate during moderate intensity exercise (p<0.05), while middle distance runners showed slight increase in blood lactate concentrations even for the first several stages. Middle-distance runners showed significantly higher amount of lactate produced (p<0.05) and greater lactate oxidation during high-intensity exercise than those in long-distance runners (p<0.01), suggesting that both lactate production and oxidation of middle-distance runners were greater than those of long-distance runners during high-intensity exercise. These results suggest that characteristics of lactate metabolism in middle- and long-distance runners depend partly on exercise intensity.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Endothelin-1 stimulated human preadipocyte growth through the AMPK, ERK, cJUN, PKC, and STAT3 pathways
Authors: Hsiao Po-Jen , Siao An-Ci , Kuo Chih-Chun , Shih Li-Jane , Kao Yung-Hsi
Published: May 2024

High level of plasma endothelin (ET)-1 was noticed in obesity, and it was found to regulate adipogenesis and the endocrine activity of fat cells. However, relatively little is known about the ET-1 signaling pathway in preadipocyte growth. Our previous reports have shown that ET-1 and ET-3 stimulated murine 3T3-L1 preadipocyte growth through different kinase signaling cascades with ET type A receptor (ETAR) but not ETBR dependency. In this study, the hypothesis arose that ET-1 may regulate human visceral white preadipocyte growth through the AMPK, ERK, cJUN, PKC, and STAT3 pathways with ET receptor-specific dependency. As indicated by an increased number of cells and greater conversion of 3-4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide (MTT) to formazan crystals by living cells, the stimulation of human preadipocyte growth by ET-1 depended on concentration. Neither ET-2 nor ET-3 stimulated human preadipocyte growth. When signaling pathways were examined, ET-1 signaling stimulated phosphorylation of AMPK, ERK, cJUN, PKC, and STAT3, proteins but not AKT, JNK, or p38 MAPK. Treatment with an ETAR antagonist, such as BQ610, or an ETBR antagonist, such as BQ788, blocked the ET-1-induced increase in cell growth and phosphorylated levels of AMPK, PKC, and STAT3 proteins. However, treatment with BQ788 but not BQ610 blocked the ET-1-increased levels of ERK and c-JUN protein phosphorylation. In addition, pretreatment with specific inhibitors of AMPK (compound C), ERK1/2 (U0126), JNK (SP600125), JAK2/STAT3 (AG490), or PKC (Ro318220) prevented the ET-1-induced increase in cell growth and reduced the ET-1-stimulated phosphorylation of AMPK, ERK1/2, c-JUN, STAT3, and PKC. However, neither the p38 MAPK antagonist nor the ceramide synthase inhibitor altered the effect of ET-1. The results indicate that the target molecules of ETAR and ETBR signaling pathways transducing ET-1 growth signals in human visceral preadipocytes can be similar (e.g., AMPK, JAK2/STAT3, and PKC) or different (e.g., ERK1/2 and JNK/c-JUN).

This work was supported in part by the National Science and Technology Council, Taiwan, Grant NSTC 112-2320-B-008-001 to YHK and the Taoyuan Armed Forces General Hospital, Taiwan, Grant AFTGH to PJH, CCK, LJS, and YHK.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
AKAP2 plays a pivotal role in renal acid-base homeostasis during metabolic acidosis
Authors: Belaid Houwayda , Morla Luciana , Wang Dongmei , Van Bemmelen Miguel , Diviani Dario , Crambert Gilles , Staub Olivier
Published: May 2024

Reversible phosphorylation and dephosphorylation of kidney proteins modulate their activities and localization and play a central role in maintaining fluid and acid-base homeostasis. The proximal tubule and the intercalated cells of the nephron are main sites of acid-base balance. It was previously demonstrated that some kidney transporters involved in the pH homeostasis were regulated by the c-AMP/Protein Kinase A (PKA) signaling pathway.The A-Kinase anchoring protein 2 (AKAP2), is a scaffold protein that binds to the Protein Kinase A (PKA) allowing the phosphorylation of target proteins but is also known to interact with Protein Phosphatase 1 and consequently contributes to protein dephosphorylation. In this study, we hypothesize that AKAP2 regulates the activity and localization of renal transporters during metabolic acidosis. An inducible and nephron-specific Akap2Pax8/LC1 knockout mouse model was generated. Fluorescent immunostaining showed that AKAP2 is present in the tubules mainly at the apical plasma membrane. AKAP2 knock-out mice in normal conditions presented an acidic urine pH and polyuria compared to control mice. Ex-vivo data from micro-perfused CCDs demonstrated a higher Na+ reabsorption and K+ secretion in AKAP2 KO mice. This suggests its importance in maintaining acid-base balance even under physiological conditions. Moreover, when treated with an ammonium chloride diet, KO mice were sensitive to the acid load; showed a lower blood pH, hyperchloremia, a lower bicarbonate level and a two-fold higher blood ammonia. The sensitivity of the KO mice further supports the role of AKAP2 in acid-base homeostasis. Although we think this is due to renal acid-base transporters activity deregulation, the consideration of a potential defect in water reabsorption mechanisms contributing to acidosis is also valid. Our study provides valuable insights into the role of AKAP2 in maintaining fluid and acid-base homeostasis in the kidneys. The findings open avenues for further research into the molecular mechanisms underlying AKAP2-mediated regulation of renal transporters and its impact on acid-base balance.

Swiss National Science Foundation (SNSF).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
White Matter Microstructure of the Genu of the Corpus Callosum Measured Using Neurite Orientation Dispersion and Density Imaging (NODDI) Is Associated with Cardiorespiratory Fitness in Older Adults
Authors: Miller Kathleen , Howery Anna J. , Corkery Adam , Loggie Nicole A. , Eldridge Marlowe , Barnes Jill N.
Published: May 2024

Changes in white matter microstructure of the genu of the corpus callosum are predictive of cognitive decline in patients with mild cognitive impairment. Cardiorespiratory fitness (CRF) is positively associated with brain health; however, the relationship between cardiorespiratory fitness and white matter microstructure of the genu of the corpus callosum is unknown. Further, a novel diffusion method for assessing white matter microstructure, neurite orientation dispersion and density imaging (NODDI), can detect specific microstructural features that are not observed with conventional diffusion tensor imaging (DTI). Young (n=27, age=25±5, m=12, f=15) and older (n=23, age=64±5, m=12, f=11) adults free of underlying disease participated in this study. CRF was assessed using an incremental maximal exercise test on a cycle ergometer. On a separate visit, white matter microstructure of the genu of the corpus callosum was measured using both DTI and NODDI MRI scans. In young adults, there were no associations between CRF and white matter microstructure of the genu of the corpus callosum measured using either DTI or NODDI (p>0.05). In older adults, there were no associations between CRF and white matter microstructure of the genu of the corpus callosum measured with DTI. However, in older adults, there was a positive association between CRF and orientation dispersion index of the genu of the corpus callosum measured with NODDI (r=0.47, p=0.02). In conclusion, using conventional DTI, no associations between CRF and white matter microstructure of the genu of the corpus callosum were observed. However, using NODDI, which can detect specific microstructural features, our results suggest that older adults with higher CRF demonstrated enhanced white matter microstructure, specifically orientation dispersion index, of the genu of the corpus callosum. Conventional DTI may underestimate the impact of CRF on age-related changes in white matter microstructure.

National Institutes of Health - HL118154 (JNB), HL007936 (KBM).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) in regulating mitochondrial energy effciency in skeletal muscle
Authors: Karasawa Takuya , Choi Ran Hee , Meza Cesar , Funai Katsuhiko
Published: May 2024

Previous studies have shown that exercise training improves mitochondrial energy effciency in skeletal muscle, but the molecular mechanism is unclear. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a transcriptional co-activator that coordinately regulates exercise-induced mitochondrial biogenesis and quality control. This study aimed to test the hypothesis that PGC-1a is involved in the improvement of mitochondrial energy effciency in skeletal muscle by using a skeletal muscle-specific PGC-1a overexpression mouse model. Ten to twelve-week-old skeletal muscle-specific PGC-1a transgenic mice (MCK-PGC-1a) and their wildtype littermates (WT) were used. Protein levels of oxidative phosphorylation (OXPHOS) subunits in skeletal muscle were determined by Western blot analysis. The rate of O2 consumption ( JO2) and ATP production ( JATP) in isolated mitochondria from skeletal muscle were evaluated using high-resolution respirometry and fluorometry, respectively, and mitochondrial energy effciency (ATP produced per O2 consumed, or P/O) was calculated. Overexpression of PGC-1a in skeletal muscle did not affect body weights and muscle weights. Consistent with previous studies, MCK-PGC-1a mice had significantly higher OXPHOS protein content than WT mice. On the other hand, JO2, JATP, and P/O in isolated muscle mitochondria were not different between genotypes. Our results suggest that exercise training-induced improvement in muscle mitochondrial energy effciency is not mediated by PGC-1a.

This research is supported by NIH grant DK107397 to K.F.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Spontaneous Bursts of Muscle Sympathetic Nerve Activity Reduce Femoral Arterial Compliance in Humans
Authors: Young Benjamin , Kissell Claire , Conley Rie , Vranish Jennifer , Credeur Daniel , Holwerda Seth , Fadel Paul
Published: May 2024

Previous studies in rodents have demonstrated tonic sympathetic restraint of arterial compliance. To date, studies in humans have examined sympathetic restraint of compliance via either reflexively or pharmacologically manipulating sympathetic vasoconstriction and measuring resultant changes in compliance. The extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) dynamically regulate arterial compliance in humans on a beat-by-beat basis remains unknown. Herein, we hypothesized that femoral arterial compliance would be transiently reduced following spontaneous bursts of MSNA. Further, we hypothesized that the magnitude of reduction in arterial compliance would be graded to the MSNA burst amplitude (index of net neural outflow). Beat-to-beat blood pressure (BP; Finometer), heart rate (ECG), MSNA (peroneal microneurography), and femoral artery blood flow (duplex Doppler ultrasound) were continuously measured over 10-20 minutes of quiet supine rest in 27 young, healthy men (age: 22 ± 1 years, resting MSNA burst frequency: 11 ± 5 bursts/minute). Customized labview programs were used to time-align neural cardiovascular variables with ultrasound data sampled at 30Hz, enabling the quantification of arterial compliance on a beat-by-beat basis defined as the change in arterial cross-sectional area divided by the change in blood pressure over the cardiac cycle. Bursts of MSNA were tracked for 10 cardiac cycles and changes in arterial compliance were quantified using signal-averaging for all bursts, and subsequently, for bursts of MSNA when sub-classified based on amplitude into quartiles (Q1= smallest 25% of bursts, Q4= largest 25% of bursts). Reductions in arterial compliance were significantly greater following cardiac cycles with bursts of MSNA compared to cardiac cycles without bursts of MSNA (bursts: -5.1 ± 0.6% vs. non-bursts: -0.8 ± 0.2%, p<0.001). Further, reductions in compliance appeared to be graded to MSNA burst amplitude (Q1: -6.5 ± 0.8%; Q4: -9.1 ± 1.3%, P=0.051). The latency (i.e., number of heartbeats) to nadir arterial compliance following bursts of MSNA was 4.2 ± 0.6 cardiac cycles. Collectively, these findings suggest that the sympathetic nervous system dynamically regulates femoral arterial compliance on a beat-to-beat basis.

College of Nursing and Health Innovation, University of Texas at Arlington.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Integrating Health Policy Into Undergraduate Physiology: A Pedagogical Framework
Authors: Redden John , Divino Jeffrey
Published: May 2024

Evidence-based health policies save lives. Rising to meet the global health challenges of the 21st century (e.g., the climate crisis, infectious diseases, health inequity) will require more scientists to participate in the policymaking process. However, few opportunities exist for STEM students to learn how their scientific knowledge can be applied to policy, or how they can shape the policies that govern science in the United States. Additionally, although scientific expertise is necessary to create effective health policies, it is not suffcient. For example, many scientifically sound policies (e.g., masking, vaccination) fail in the implementation phases because they are not communicated effectively to their intended audience. Here we share a pedagogical framework for integrating health policy into existing undergraduate physiology courses using examples from Anatomy and Physiology, Physiological Model Systems, and Public Communication of Physiology. This framework empowers students to develop procedural knowledge about state and federal policymaking, discuss examples of biomedical scientists and healthcare workers contributing to policy and rulemaking, link course curricula to current legislation proposed at the state or federal level, and advocate using their scientific knowledge and lived experiences as scientists. It also incorporates foundational science communication training that goes beyond the commonly used deficit framework (i.e., “educating the public”), and instead emphasizes dialogue (e.g., listening to stakeholders), rhetorical strategy (e.g., storytelling), trust-building, discrete goal setting, and positionality. Lastly, we provide preliminary evidence that using this health policy toolbox leads to student empowerment in policy and advocacy, development of practical communication skills applicable to their future careers, and deep affective connections to their physiology coursework.

This project was supported by the Alan R. Bennett College of Liberal Arts and Sciences Public Health Policy Research Fund at the University of Connecticut.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
PNA5, a Novel Glycosylated Angiotensin 1-7 Treatment Improves Infarct Size and Fibrotic Remodeling in Ischemic Reperfusion Injury
Authors: Piepho Arian , Hoyer-Kimura Christina , Hay Meredith , Methajit Methawasin , Polt Robin , Fricks Joshua , Salcedo Victoria
Published: May 2024

Background: Reperfusion during an acute ischemic event is of paramount importance to rescue cardiac tissue. Paradoxically, reperfusion of the ischemic tissue promotes further cardiac injury. Increased reactive oxidative species (ROS) and inflammation contribute to ischemic reperfusion injury (IR). PNA5, a glycosylated analog of angiotensin-(1-7), decreases ROS and inflammation. The purpose of this study is to indicate if PNA5 treatment has the ability to reduce infarct (IN) size and improve cardiac remodeling in IR. We hypothesize that PNA5 will improve fibrosis and diminish IN size in IR. Methods: 3-month-old male mice (C57BI/6J) underwent IR surgery. Mice were anesthetized and the left anterior descending artery was litigated for 45 minutes. Ischemic areas were then reperfused. Mice were immediately injected with PNA5 (subcutaneously s.c. at 100μg/kg, n=11) or with saline as control (n=11). Injections were continued daily with PNA5 or saline for 8-weeks. At the end of treatment, mice were sacrificed. Upon sacrifice, hearts were re-ligated and perfused with Evans Blue to identify the areas at risk (AAR). Hearts were stained with 2-3-4-triphenyltetrazolium chloride to show IN area. IN size and AAR were determined using Image J. Paraffn-embedded hearts were stained with Picrosirius Red for fibrosis. Fibrosis was measured as a ratio of collagen to total tissue area for 17 regions in the left ventricle (LV). Values are represented as mean ± standard error of mean. Results: PNA5-treated mice IN size was significantly decreased compared to saline-treated mice. (IN/AAR: IR-Saline 0.17± 0.02; PNA5 0.10± 0.01, p=0.005; IN/LV: IR-Saline 0.08± 0.01; PNA5 0.05±0.01; p=0.002, student’s T-test). PNA5 reduced fibrosis in the LV compared to IR-saline mice Conclusions: These results indicate PNA5 as a potential therapeutic treatment for IR as it improves IN size and fibrotic remodeling in IR.

[Formula: see text]

Supported by NIA U01AG066623 to MH.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effects of p300 inhibition on prostate cancer cell growth
Authors: Kunkel Olivia , Horn Andrew , Wallace Nicholas , Behnke Bradley
Published: May 2024

Background: Radiation is a central component of many anti-cancer therapy regimens, utilized for more than half of all cancer patients. Despite advances in the delivery and success of radiation treatment, many individuals express, or will develop, radioresistance, a major contributor to treatment failure and malignant progression. While the etiology of radioresistance is complex, it may be mediated in part by expression of p300, a histone acetyltransferase known to facilitate DNA repair. We hypothesized that inhibition of p300 would increase radiosensitivity of prostate cancer cells in vitro. Methods: Human prostate adenocarcinoma (PC-3) cells were grown in tissue culture flasks incubated at 37° C with 5% CO2. Cells were randomized to receive 1 μM CCS 1477, a selective inhibitor of p300, or vehicle for 1 hour prior to a single treatment of 0 Gy (NR+ or NR-, respectively) or 2 Gy radiation (R+ or R-, respectively). Four hours after radiation, cells were seeded into 100 mm diameter tissue culture dishes and incubated for 10 days. Cells were then stained, and colonies > 50 cells were counted to determine clonogenic survival. Cell survival was corrected for plating effciency and group comparisons were made using a two-way ANOVA. Results: Results were determined from the average of 3 separate experiments. Compared to non-radiated controls (NR-), survival of R- was reduced to 47%, while survival of R+ was reduced to 32%. However, there was no significant difference between % survival of R- and R+. Conclusions: In vitro, 1 μM exposure to CCS 1477 does not reduce clonogenic survival in PC-3 cells subjected to 2 Gy radiation. The duration of exposure and concentration of CCS 1477 may not be adequate to elicit significant improvements in radiosensitivity of PC-3 cells to 2 Gy radiation. Future experiments will explore the effects of varying durations of exposure and concentrations of CCS 1477. Additionally, it remains to be determined whether CCS 1477 improves radiosensitivity in other cancer cell lines (e.g., breast cancer).

Johnson Cancer Research Center.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Gestational Long Term High-Altitude Hypoxia and Metabolomic Reprogramming in Uterine Arteries of Adult Sheep
Authors: Cosper Justis , Zhang Lubo , La Frano Michael , Wilson Sean
Published: May 2024

Long term hypoxic stress during pregnancy causes a reduction in uterine blood flow, compromising oxygen and nutrient delivery to the fetus. There are multiple epigenetic factors involved in the structural and functional impairments that underlie the impairments in uterine arterial function. Evidence indicates that oxidative stress plays an important role to the decrements in blood flow following high altitude pregnancy. The purpose of the current study was to test the hypothesis that changes in oxylipin and endocannabinoid signaling are important to the increases in oxidative stress along with changes in glucose and fat metabolism. To further understand the mechanisms associated with disruption of uterine artery blood flow due to high altitude pregnancy, we examined a high altitude pregnant sheep model. Pregnant and non-pregnant sheep were housed either at low (700m) or high altitude (3801 meters) for 110+ days of pregnancy. Uterine arteries were excised from pregnant and non-pregnant sheep and targeted as well as untargeted metabolomic analyses were performed to test the hypothesis that hypoxia increases oxidative stress and reduces oxidative metabolism. Enrichment analysis of the metabolites show that hypoxia impacted several key biochemical pathways. At high altitude there were decreases in Alpha Linolenic Acid and Linoleic Acid Metabolism along with reductions in Pyruvate Metabolism and antioxidants. Further to this, there was an increase in the metabolism of Arachidonic Acid, Glycerolipids, and Methionine, which are linked to inflammation, cell signaling, and cell growth. Fully understanding how increased oxidative stress and inflammatory pathways along with decreased antioxidant capacity and changes in cellular metabolism is tied to malformations in uterine arterial structure and function following high altitude gestation is an active area of investigation.

This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine and West Coast Metabolomics Center.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Prenatal transportation stress and sex influence the metabolomic profile of the liver of 28-day-old Brahman bulls and heifers
Authors: Welsh Thomas H. , Tolleson Douglas R. , Cardoso Rodolfo , Haigrove Thomas , Riley David , Long Charles , Perry George
Published: May 2024

Prenatal transportation stress (PNS) reportedly induced differential DNA methylation of genes related to behavior, immune function, stress response, and metabolism in Brahman heifer and bull calves (doi:10.1093/jas/skz368). The objective of the present experiment was to conduct a metabolomics analysis of liver samples of 25-day-old beef calves to identify biochemicals and determine effects of PNS and sex classification. Mature Brahman cows artificially inseminated to the same Brahman sire were assigned to be either Control (n=35; not transported) or PNS (n=37; 2 h of transportation at 60, 80, 100, 120, and 140±5 d of gestation). Livers were obtained from 16 Control (8 bulls and 8 heifers) and 16 PNS (8 bulls and 8 heifers) calves that were humanely euthanized at 25±2 d of age. Liver samples (200 mg) were submitted to Metabolon, Inc. to identify metabolites by ultra-high-performance liquid chromatography/tandem high resolution/accurate mass spectrometry chromatography methods. An estimate of the false discovery rate was calculated and following log transformation, two-way ANOVA was used to identify significant interactions and biochemicals that differed significantly ( p ≤ 0.05). Principal component analysis (PCA) was also used to compare PNS and sex effects. A total of 851 biochemicals were identified and categorized; this report emphasizes energy pathways and lipid mediators of inflammation. PNS increased 45 metabolites and decreased 21 whereas 23 were increased and 30 decreased in bulls versus heifers. Significant interaction of PNS and sex was noted for 33 metabolites. Glucose did not differ due to PNS; however, it was increased in bulls versus heifers. Maltotriose and maltose were higher in PNS, and it was greater in heifers than bulls. Lactate was higher in bulls than heifers. Lipid mediators of inflammation were elevated in PNS calves. to our knowledge this is the first report on the liver metabolome of prenatally stressed calves. These observations suggest an influence of prenatal stress and sex on liver metabolomics within 1 month of age in cattle.

USDA NIFA Award No. 2019-67015-29573.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Investigating the role of Vitamins in Prostate cancer risk among African Americans
Authors: An William , Ukoli Flora , Raynes Edilberto
Published: May 2024

Background & Aims: Previous studies have shown certain vitamins and minerals are associated with a reduced risk of prostate cancer. In this study, we assess whether vitamins will have an effect on prostate cancer risk among African Americans. Methods: A case-control study was conducted in Washington, District of Columbia and Nashville, Tennessee. There were 264 participants involved in the study. The participants were divided into 3 groups: prostate cancer (n=56), elevated PSA (n=377) and control (n=163). Dietary intake was measured by using a validated food frequency questionnaire. Food items rich in vitamin D, vitamin E, selenium, and lycopene were identified. Chi square tests were performed to evaluate the association between vitamins and prostate cancer risk. Results: There is a statistically significant association between the consumption of certain food items such as beef, pork, eggs and decreased prostate cancer risk (p<.05). There is also a statistically significant association between the consumption of salmon, cod liver oil, peanuts, mushrooms, orange juice and prostate cancer risk increase (p<.05). When aggregated, there was no significant correlation between the consumption of vitamin D, vitamin E, lycopene, selenium and decreased prostate cancer risk. Conclusions: Results of our case-control study suggest dietary restriction of certain meats as prostate cancer risk reduction strategy cannot be suggested. Increasing annual intake of food high in vitamin D, vitamin E, selenium, and lycopene cannot be suggested as a way to decrease prostate cancer risk. Diet modification interventions should focus on dietary moderations.

Center of Excellence COE/Offce of Dean, Meharry Medical College School of Medicine, Grant Number: D34HP16299.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Changes of Inflammatory Cytokines after 4-week and 8-week Aerobic Exercise in Hispanic Obese Females
Authors: Yoemans Kylie , Park Kyung-Shin , Gutierrez Monica , Chavarria Raul , Rodriguez Marielise , Park Jeffrey
Published: May 2024

Recent studies have insuffcient data to support the effects of exercise on inflammatory cytokines independent from weight loss. Thus, a reduction in fat mass is required to induce decreases in markers of pro-inflammatory cytokines. PURPOSE: Changes in inflammatory cytokines following 4-weeks and 8-weeks of aerobic exercise were measured in this study to find if exercise is an independent determinant on changes in inflammatory cytokines in middle-aged Hispanic obese females. Methods: 35 obese females were randomly assigned to either exercise (EX, N=16) or control (CON, N=19) group. The exercise group performed moderate intensity aerobic exercise on the treadmill for 60 minutes at 55% of VO2max for 8 weeks (3 days/week). Body composition measurement with dual-energy X-ray absorptiometry and blood collection were conducted before and after the 4th week and 8th week of the intervention (PRE, 4W, and 8W). Blood samples were used to measure levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and adiponectin. Two-way repeated measures ANOVA and Tukey post hoc tests were used for data analysis. RESULTS: Following 8 weeks of aerobic exercise intervention, participants had significantly reduced body mass index (34.2±4.6 mean±SD → 33.7±4.7, P=.035), %body fat (42.1±5.2% → 41.4±5.3, P=.014) and TNF-α (4.57±.24pg/mL mean±SE → 4.14±.31, P=.019) as compared to PRE. EX also observed a decrease in TNF-α (4.57±.24 → 4.29±.28, P=.033) when changes in body weight and %body fat were not observed after 4 weeks of aerobic exercise. CRP and adiponectin were unaltered in EX. CON showed no significant changes in any variables at 4W and 8W. CONCLUSION: It is suggested reductions in inflammatory cytokines are associated with fat loss; however, significant change in TNF- α at 4W when no change in %body fat is observed this indicates that moderate aerobic exercises may reduce level of inflammation independent from fat loss. This change is further improved when fat loss occurs at 8W. Therefore, it is plausible that moderate aerobic exercises may independently reduce risks of obesity-associated disorders in middle-aged Hispanic obese females. Results of this study suggest that longer periods of exercise training with fat loss may be required to induce significant changes in CRP and adiponectin in middle-aged obese females.

TAMIU University Research Grant.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sphingosine-1-Phosphate Promotes Resiliency to External Stress in the Human Microvasculature
Authors: Cohen Katie E. , Bordas-Murphy Henry , Durand Matthew J. , Freed Julie K.
Published: May 2024

Exposure to external stress (e.g. high pressure, high glucose) promotes human microvascular endothelial dysfunction and reduces the overall magnitude of flow-induced dilation (FID). We have previously shown that treatment with sphingosine-1-phosphate (S1P), a sphingolipid known to activate pro-survival pathways in endothelial cells, restores nitric oxide (NO) as the primary mediator of flow-induced dilation (FID) in arterioles from patients with coronary artery disease. Whether pre-treatment with S1P can prevent stress-induced microvascular endothelial dysfunction remains unknown. Our hypothesis is that pre-conditioning with S1P will promote resiliency to external stress (high intraluminal pressure) and prevent stress-induced reduction of FID. Human resistance arterioles (100-250μm) from otherwise healthy adults (one risk factor or less for coronary artery disease) were dissected from discarded surgical adipose tissue and treated with S1P (1μM) or vehicle control for 16-20 hr prior to the flow experiment. Vessels were cannulated for videomicroscopy and stressed with elevated intraluminal pressure (150mmHg, 30 min) then pre-constricted with endothelin-1 prior to initiating flow to elicit dilation. Arterioles treated with vehicle and exposed to high intraluminal pressure exhibited an overall reduction in vasodilatory capacity to flow (37.3%±8.6) compared to non-stressed, vehicle treated microvessels (66.1%±5.5). However, the ability to dilate to flow was preserved in microvessels pre-treated with S1P and exposed to high pressure (74.8%±6.7) compared to vehicle and high pressure (37.3%±8.6). These data suggest that S1P-activated pathways may foster resilience by reversing stress-induced microvascular endothelial function. Targeting S1P signaling may offer a novel therapeutic strategy to prevent microvascular dysfunction and the myriad diseases it causes, such as large vessel atherosclerosis, and heart failure with preserved ejection fraction.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Spontaneous Sympathetic Baroreflex Sensitivity Is Impaired in Patients with Chronic Kidney Disease
Authors: Sabino-Carvalho Jeann , Zanuzzi Matias , Li Sabrina , Park Jeanie
Published: May 2024

Patients with chronic kidney disease (CKD) have chronic overactivation of the sympathetic nervous system that contributes to hypertension and increased cardiovascular risk. The sympathetic baroreflex is a major regulator of sympathetic activity in response to changes in blood pressure; however, limited information is available regarding sympathetic baroreflex control in non-dialysis patients with CKD. In the present study we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) is attenuated in non-dialysis patients with CKD. In 17 sedentary patients with CKD stages III-IV (76% hypertensive and 29% with diabetes) [12 male/5 female, age: 57 ± 13 yr, 13 Black/4 White, systolic/diastolic BP: 122 ± 17/75 ± 7 mmHg, BMI: 31 ± 5 kg/m2, eGFR: 40 ± 14 mL/min/1.73m2] and 9 controls (CON) (89% hypertensive and 22% with diabetes) [7 male/2 female, age: 51 ± 13 yr, 8 Black/1 White, systolic/diastolic BP: 123 ± 6/79 ± 6 mmHg, BMI: 30 ± 6 kg/m2, eGFR: 95 ± 12 mL/min/1.73m2], resting beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography) were continuously recorded during 10 min of semi-recumbent rest. Weighted linear regression analysis between MSNA burst incidence and diastolic blood pressure was used to determine the spontaneous sympathetic baroreflex sensitivity (sBRS). Resting MSNA burst incidence was higher in patients with CKD [CKD: 70 ± 19 bursts (100 heart beats)−1. mmHg−1 versus CON: 47 ± 9 bursts (100 heart beats)−1. mmHg−1; p<0.001], and a higher MSNA burst frequency was observed in CKD (CKD: 43 ± 11 bursts. min−1 versus CON: 32 ± 10 bursts. min−1; P=0.021], whereas resting mean arterial blood pressure (91 ± 9 mmHg versus 94 ± 5 mmHg; P=0.317) and heart rate were similar between groups. Patients with CKD had reduced sBRS compared to controls [CKD: -1.37 ± 0.59 bursts (100 heart beats)−1 mmHg−1 versus CON: -2.79 ± 1.33 bursts (100 heart beats)−1 mmHg−1; P=0.013]. The MSNA burst incidence (r = -0.63, p<0.001) and the sBRS (r = -0.57, P=0.002) were significantly associated with the estimated glomerular filtration rate (eGFR). Overall, these preliminary findings suggest an attenuated sympathetic baroreflex sensitivity in patients with CKD compared with age and-comorbidities matched controls, with greater impairment in those with more severe kidney dysfunction.

This work was supported by National Institutes of Health Grants R01HL135183 and R61AT010457 (J.P).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The type of fatty acid dictates their impact on gut permeability and nutrient absorption
Authors: Evangelista-Silva Paulo Henrique , Prates Rodrigo Pereira , de Faria Rodrigo Lucas , Bargi-Souza Paula , Miyamoto Sayuri , Anhe Fernando Forato , Goulart-Silva Francemilson
Published: May 2024

We showed that short- and long-term (3 to 12 weeks) high-fat diet (HFD) feeding reduced protein expression of nutrient transporters in the proximal jejunum of mice. The most abundant fatty acids (FA) in HFD were oleic (OA), palmitic (PA) and stearic (EA) acid. Because PA and EA are generally regarded as pro-inflammatory, we hypothesize that dietary PA and EA alter gut permeability and absorption via inflammatory activation. To test this hypothesis, we orally administered HFD-matched doses of OA, PA, and EA to male C57BL/6 mice, fed on purified diet control (LFD), for 3 weeks. Food intake and body weight were monitored, and composition were also evaluated. We next qPCR-assessed the mRNA expression of cytokines ( TNF-α, IL-6, IL-1β, IFN-γ, IL-10) and inflammatory signaling transducers ( MD-2 and Myd88) as well as the protein content of nutrient transporters (Glut2, Pept1, Fat/cd36 and Npc1l1) and cell-cell adhesion proteins (Occludin) in the gut. Small intestinal permeability was assessed ex vivo and gut morphology was histologically determined. In addition, Caco-2 enterocytes were used to assess the impact of specific cytokines on nutrient transport and gut barrier integrity. All dietary FA reduced food intake without affecting lean or fat mass. In the jejunum, OA increased TNF-α gene expression whereas PA upregulated IFN-γ and MD-2 gene expression. Furthermore, OA reduced the nutrient transporters Glut2, Pept1, and Fat/cd36 without affecting Npc1l1, whereas PA and EA reduced Occludin protein content. PA, but not OA and EA, increased jejunum paracellular permeability ex vivo and increased villus length. In Caco-2 cells, while Tnf-α did not affect Glut2, Pept1 and Fat/cd36 or Npc1l1 content, Ifn-γ downregulated Occludin protein content. We conclude that OA and, more potently, PA exert inflammatory effects which contribute to damage gut barrier integrity and downregulate nutrient absorption. Our data point to IFN-γ as a main player coupling dietary stress from PA to altered gut homeostasis.

Funding: FAPESP (grants number: 2014/12871-9, 2019/05086-7, 2020/12201-4, and 2022/14545).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.