bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Chronic Doxorubicin Administration on Satellite Cell Population and Capillary Density in Multiple Skeletal Muscles
Authors: D'Lugos Andrew C. , Fry Christopher S. , Hale Taben M. , Gonzales Rayna J. , Angadi Siddhartha S. , Carroll Chad C. , Dickinson Jared M. 
Published: June 2021

Anthracyclines are mainstay chemotherapeutic agents proven effective at reducing disease recurrence and mortality in breast cancer patients. However, these drugs also have harmful side effects that include skeletal muscle wasting. The purpose of this study was to assess the impact of bi‐weekly doxorubicin (DOX) administration on the satellite cell population and capillary density in multiple skeletal muscles. We hypothesized that DOX treatment would reduce fiber size, along with the satellite cell population and capillary density of the soleus (SOL) and extensor digitorum longus (EDL) muscles. Eight‐week old ovariectomized female Sprague‐Dawley rats were randomized to one of two treatments: DOX and vehicle (Veh). DOX (4 mg/kg) or Veh (saline) intraperitoneal injections were performed bi‐weekly for a total of 3 injections (cumulative dose 12 mg/kg). Animals were euthanized 5d following the last injection, during which the SOL and EDL were dissected and prepared for immunohistochemical analysis. Relative to Veh, cross‐sectional area (CSA) of the SOL and EDL muscle fibers were 30% and 45% smaller, respectively, in DOX (p<0.05 vs. Veh). The satellite cell population and capillary density were 40% and 35% lower, respectively, in the SOL of DOX‐treated versus Veh‐treated rats (p<0.05), whereas the satellite cell population and capillary density in the EDL were unchanged by DOX (p>0.05). Chronic doxorubicin administration is associated with reduced fiber size in multiple skeletal muscles, however doxorubicin appears to impact the satellite cell population and capillary density in a muscle‐specific manner.Support or Funding InformationIntramural funds from Arizona State University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating the Role of mTORC1 in the Androgen‐Mediated Regulation of Skeletal Muscle Growth
Authors: Rossetti Michael L. , Gordon Bradley S. 
Published: June 2021

Androgens play an important role in regulating skeletal muscle growth largely through changes in muscle protein balance (synthesis + breakdown). Despite this, the underlying molecular mechanism(s) by which androgens alter protein balance and subsequent muscle growth are poorly defined. Previous research has implicated signaling through the mechanistic target of rapamycin complex 1 (mTORC1) in the androgen‐mediated regulation of protein balance as phosphorylation of mTORC1 substrates that control both protein synthesis and protein breakdown have been shown to be altered by androgen depletion/treatment. However, the role of mTORC1 in the androgen‐mediated regulation of muscle growth in vivo has yet to be defined. To define this role, 10‐week old male mice were randomized into four groups of equal body weight, subjected to a sham or castration surgery, then allowed to recover for 7 weeks to induce muscle atrophy in the castrated groups. Following the recovery, sham and castrated mice were implanted with either a control pellet or a pellet designed to release rapamycin at a rate of ~3 mg/kg of body weight/day over a period of 60 days. One‐week post implantation, a group of castrated mice implanted with either control pellets or rapamycin pellets began receiving weekly, intramuscular injections of nandrolone decanoate (ND) to induce muscle regrowth. All other sham and castrated mice received vehicle only. Mice were treated with vehicle or ND for 6 weeks (42 days). The tibialis anterior (TA) was harvested for analysis. The efficacy of the rapamycin pellets to inhibit mTORC1 was confirmed by the inability of insulin to increase phosphorylation of mTORC1 substrates [i.e. 70 kDa ribosomal protein S6 kinase 1 (Thr389), eIF4E binding protein 1 (Ser65), and uncoordinated like kinase 1(Ser757)] in mice receiving rapamycin even though induction of Akt (Thr308) phosphorylation was unaffected. Castration reduced TA wet weight and muscle fiber cross sectional area (CSA), but these values were restored to sham levels with ND administration, even in the presence of rapamycin. Further, the protein content of the TA was also decreased by castration, and ND administration restored this value to sham levels even in the presence of rapamycin. These changes in protein content were not due to changes in the translational capacity of the muscle as RNA content was similar across treatments. In all, these data indicate that androgens alter protein balance and muscle regrowth in an mTORC1‐independent manner.Support or Funding InformationStart‐up funds from the University of Central FloridaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sarcopenia‐Associated Plasma Biochemistry of Community‐Based Women Enrolled in a Lifestyle Modification Program
Authors: Barros Layene Peixoto , Kano Hugo Tadashi , Manda Rodrigo Minoru , Bernardino Caroline , Nakagaki Mariana Santoro , Burini Roberto Carlos 
Published: June 2021

RATIONALESarcopenia is one of major currently illness associated with contemporary behaviors and having metabolic outcomes yet to be clarified.PURPOSEThis study aimed to identify demographic, socioeconomic, physical activity and particularly clinical‐biochemical factors associated with muscle mass hypotrophy in community‐based women screened for a lifestyle modification program.METHODSBaseline data were analysed from 996 women (55.7 ± 15.9 years old), clinically selected for the “Move for Health” lifestyle modification program during 2005 to 2016. The cross‐sectional analysis had muscle mass as independent variable and the co‐variables demographic, socioeconomic, physical activity, anthropometry, and biochemical data. Muscular Mass Index (kg muscle mass/m2 height =MMI) data was splitted into quartiles for the co‐variables distribution and analysis by Statistica 10.0 software, with p <0.05 as significant.RESULTSWomen with lower muscle mass (Q1) were older, with incomplete elementary education, low family income, presenting poor perception of health status and classified at the lowest level of weekly physical activity. The lower muscle mass was accompanied by higher values of TG, hs‐CRP, fasting glucose and HOMA‐IR, and lower values of HDL‐col, uric acid, albumin and leukocytes. By 92% of Q1 could be attained by the plasma variables HDL‐col, HOMA‐IR and hs‐CRP, in descending order of magnitude.CONCLUSIONMuscle hypotrophy of adult female is associated with increased inflammatory and pro‐oxidant markers, characteristics of aging, lower socioeconomic status and low physical activity levels.Support or Funding InformationSupported by CNPq and CAPESThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Preventive effects of capillary regression on Brazilian honeybee propolis in disused skeletal muscle of rats
Authors: Fujino Hidemi , Kondo Hiroyo , Matsumoto Tomohiro , Ono Kohei , Ikeji Takuya , Takuwa Miho , Hirabayashi Takumi , Ishihara Akihiko 
Published: June 2021

PURPOSEA chronic decrease in activity results in muscle capillary regression that is due, in part, to the overproduction of reactive oxygen species. Brazilian propolis (BP) is natural polyphenol‐rich substance collected by honeybees. The purpose of the present study was to investigate the protective effects of BP supplementation on capillary regression in hindlimb unloading‐induced atrophied soleus muscle.METHODSTwenty‐eight male Wistar rats were assigned randomly either to a control, control with BP supplementation, hindlimb unloaded or hindlimb unloaded with BP supplementation group for 14 days. The three‐dimensional capillary network of soleus muscle was visualized using a confocal laser scanning technique. The capillary volume, frequency distribution of luminal diameters and capillary‐to‐fiber ratio were measured. In addition, mojor proangiogenic factors, VEGF, Flt‐1, FlK‐1, anti‐angiogenic factors, thrombospondin‐1, and oxidative stress maker were determined.RESULTSThe capillary volume, luminal diameter and capillary‐to‐fiber ratio in atrophied muscle were lower than those in control. BP supplementation, however, attenuated the capillary regression under disused muscle. In addition, the expression levels of thrombospondin‐1 and SOD‐1 were decreased and the level of VEGF was increased in BP supplemented muscle. Furthermore, TUNEL‐positive endothelial cells in BP supplemented muscle were decreased although TUNEL‐positive endothelial cells in atrophied muscle were increased.CONCLUSIONThese results suggest that Brazilian propolis supplementation may be an effective treatment to counter the regression of muscle capillary under disuse condition.Support or Funding InformationSupported by Yamada Research Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Estrogen‐related Receptor α Overexpression Drives a Metabolic and Gene Expression Program Mimicking Aerobic Exercise in Skeletal Muscle
Authors: Huss Janice M. , Hamilton Angelica , Li Jing 
Published: June 2021

Aerobic exercise is considered one of the most effective interventions to prevent obesity and type 2 diabetes (T2D). Exercise increases skeletal muscle insulin sensitivity by stimulating mitochondrial respiration and fatty acid oxidation through coordinated regulation of metabolic genes. Transcriptional pathways that regulate exercise‐induced metabolic gene programs present an attractive class of therapeutic targets to combat obesity and related metabolic diseases. We and others have shown that the Estrogen‐related Receptor α (ERRα) nuclear receptor regulates mitochondrial biogenesis, respiration and fatty acid oxidation and is required for metabolic reprogramming in response to exercise training. The objective of these studies is to determine whether ERRα over‐expression is sufficient to mediate exercise‐induced adaptations in muscle. We generated a conditional ERRα transgenic mouse line that expresses the Flag‐tagged human ERRα in skeletal muscle‐specific manner when crossed with Mck‐Cre recombinase mice (ERRαMOE). We examined gene expression (trancript and protein) and characterized the metabolic phentoype of the ERRαMOE mice. ERRαMOE mice exhibited a reddening of the superficial gastrocnemius and quadriceps, characteristic of oxidative muscles, accompanied by a reciprocal change in myosin heavy chain (MHC) IIb (−35%) and IIa (+80%) expression. Mitochondrial content was higher in skeletal muscle and heart, but not in non‐muscle tissues, based on mtDNA quantitation and citrate synthase protein expression. Consistently, basal (+32%) and maximal (+70%) O2 consumption rates were increased in FDB fibers isolated from ERRα‐MOE compared to WT. Signaling through the AMP‐activated kinase (AMPK) pathway, which mediates exercise‐dependent metabolic reprogramming, was unchanged in the basal state; however, maximal activation by AICAR was enhanced in ERRα‐overexpressing myotubes. We assessed systemic glucose homeostasis in adult chow fed mice. Although fasting glucose (6 hr) was slightly lower in ERRαMOE, no significant difference in glucose tolerance was observed. However, the results of insulin tolerance tests showed that ERRαMOE mice were more insulin sensitive than WT. In future studies we will investigate whether ERRα activation in skeletal muscle protects against high fat diet‐induced insulin resistance. Based on the results from these studies, ERRα over‐expression mimics the effects of exercise on skeletal muscle mitochondrial respiratory capacity and improves whole body insulin sensitivity.Support or Funding InformationSupported by Diabetes and Metabolic Research Institute (DMRI) and Shared Resource Pilot Awards from the City of Hope and NIH U24DK097748This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Autophagy and mitophagy flux in skeletal muscle during chronic‐contractile activity
Authors: Kim Yuho , Triolo Matthew , Erlich Avigail , Lai Jenny , Hood David A. 
Published: June 2021

Autophagy and mitophagy are important cellular recycling mechanisms, however the regulation of autophagy and mitophagy flux in training‐induced muscle adaptations remains to be elucidated. Using the microtubule destabilizer colchicine (0.04 mg/kg), this study assessed LC3II and p62 flux in skeletal muscles of Sprague‐Dawley rats (501 ± 9 g) subjected to chronic contractile activity (CCA; 3 hours/day, 9V, 10 Hz continuous, 0.1 ms pulse duration) for 1, 2, 3, 5, and 7 days (N=6–8/group). Colchicine was given via an intraperitoneal injection 48 hours prior to tissue collection, whereas control animals were administered saline as a vehicle treatment. Following 7 days of CCA, there were significant increases in maximal state 3 respiration, accompanied by a decrease in ROS production in IMF mitochondria (P < 0.05), indicating that mitochondrial adaptations were elicited in the stimulated muscle. Notably, whole muscle autophagy flux, as measured by LC3II and p62, was downregulated in response to 3 days of CCA, and further by 7 days of CCA (P < 0.05). In addition, muscle mitochondrial LC3II flux was decreased by 3 days of CCA, indicative of reduced mitophagy. In contrast, the lysosomal system, measured by TFEB and LAMP1 protein levels, was gradually upregulated by CCA, culminating at day 7. Interestingly, the translocation of TFEB into the nucleus in response to CCA was increased at day 3 (P < 0.05). However, this nuclear TFEB was not sustained and subsequently declined back to basal levels. In conclusion, we suggest that chronic exercise can lead to muscle adaptations through a coordinated mechanism, involving a decrease in autophagy/mitophagy flux, combined with an increase in the capacity of the lysosomal system.Support or Funding InformationThis work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Altitude Hypoxia Impacts Omega‐3 Fatty Acid Metabolites in Plasma of Fetal and Newborn Sheep
Authors: Lopez Vanessa , La Frano Michael , Bosviel Remy , Newman John , Thorpe Richard , Feihn Oliver , Zhang Lubo , Wilson Sean M. 
Published: June 2021

Perinatal hypoxia has profound effect on an infant's development, with physiological impairment of multiple organ systems. The present study explored the effect of hypoxia due to long term high altitude exposure during gestation and after birth on lipid mediators by measuring the metabolites that foreshadow oxidative stress and inflammation, which are primary drivers of dysfunction. We tested the hypothesis that long term hypoxia reduces the amount of oxylipin and endocannabinoid production, which are important mediators of oxidative stress and inflammation. To test this hypothesis pregnant sheep and newborn lambs were housed at a low altitude (700 m) or exposed to an altitude of 3,800 meters starting gestation day 30. UPLC‐MS/MS analysis was used to investigate the lipid mediator composition in plasma collected from veins of near‐term fetal and newborn animals. The results show that hypoxia causes an overwhelming effect on omega‐3 fatty acids and their derivatives, which are crucial in late‐stage fetal development. Several of the omega‐3 fatty acids reduced with hypoxia have well known effects on inflammation, vascular tone, and oxidative stress. Furthermore, we tracked the origin of the identified oxylipins and endocannabinoids by tracing their pathways. The cytochrome P450 (CYP) pathway enzymes and the subsequent activity of soluble epoxide hydrolase (sEH) are prominent synthesizers of the oxylipins such as epoxyeicosatrienoic acids (EETs) and epoxyoctadecenoic acids (EpOMEs). Previous studies have suggested the role of EETs and EpOMEs in vasodilation, a feature in inflammation. Based on these findings we demonstrated that a majority of the affected oxylipins were produced from CYP and sEH enzymes, which are important to vascular function. These findings provide novel insight into our understanding of lipid metabolites to hypoxia‐induced dysfunction in the developing fetus and newborn. In the long term this may help us develop novel therapies that target inflammatory pathways induced by pre and post‐natal hypoxia.Support or Funding InformationThis material is based upon work supported by NIH grants P01HD083132 and 1U24DK097154 through a pilot project grant to Sean Wilson. VL is a recipient of the American Physiological Society's Short‐Term Research Education Program to Increase Diversity in Health‐Related Research (STRIDE) Fellowship funded by the APS and a grant from the National Heart, Lung and Blood Institute R25HL115473.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sweet Success: Metabolic Substrate Adaptations To Acute Hypoxia In The Naked Mole Rat (Heterocephalus Glaber)
Authors: Pamenter Matthew E. , Kirby Alexia M. , Shuhendler Adam J. 
Published: June 2021

Naked mole rats are among the most hypoxia‐tolerant mammals identified. This tolerance is partially achieved through their ability to coordinately reduce metabolic rates by > 85% in acute hypoxia while staying warm and active in their hypoxic underground burrows. Our understanding of the physiological responses that enable their hypoxia‐tolerance is improving; however, the underlying molecular and biochemical mechanisms that support this remarkable energetic suppression are poorly understood. Of particular interest is a putative metabolic fuel substrate switch in hypoxia. Naked mole rats primarily metabolize lipids in normoxia, but carbohydrate metabolism may be favored in hypoxia because carbohydrate oxidation yields more energy per molecule of oxygen than does lipid oxidation. We hypothesized that naked mole rats switch to primarily glucose‐fueled metabolism in acute hypoxia and that the energetic needs of brain and heart are prioritized over those of other tissues. Furthermore, we predicted that heat production from brown adipose tissue, which is a glucose‐intensive process, would be turned off in hypoxia as an energy‐saving strategy. To test these hypotheses, we measured metabolic fuel usage and heat production in naked mole rats exposed to acute hypoxia (7% O2) using non‐invasive in vivo imaging techniques, including infrared thermography, magnetic resonance imaging (MRI), and positron emission tomography (PET). We found that glucose metabolism is markedly upregulated in heart and brain during acute hypoxia, but decreased in liver. Furthermore, heat generation from brown adipose tissue is entirely turned off in hypoxia and the naked mole rat body temperature drops to near or below ambient temperature, indicating that all endogenous heat production ceases in hypoxia. We conclude that naked mole rats maximize the energy/oxygen ratio in their metabolic fuel substrate usage and prioritize feeding the energetic needs of brain and heart over all other metabolic processes in hypoxia.Support or Funding InformationThis study was supported by an NSERC discovery grant to MEP, a CIHR grant to AJS, and CRC grants to MEP and AJS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Environmental chemicals can disrupt neonatal cardiomyocyte physiology
Authors: Ramadan Manelle , Sherman Meredith , Jaimes Rafael , Swift Luther , Posnack Nikki 
Published: June 2021

BackgroundThe ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine‐disrupting chemicals in plastic production, including bisphenol A (BPA). Widespread and continuous exposure to BPA can occur through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. Recent studies have shown a link between BPA exposure and adverse cardiovascular outcomes. This is particularly concerning for vulnerable populations who are at risk of high BPA exposure due to medical treatment, including pediatric patients. Despite significant differences in the cardiac physiology of the developing and adult heart, our current understanding of BPA‐induced cardiac dysfunction has been limited to adult models.ObjectiveCardiac physiology differs significantly between the pediatric and adult heart. We aimed to determine the extent to which BPA exposure contributes to cardiovascular dysfunction, using a neonatal cardiomyocyte model.MethodsNeonatal rat ventricular myocytes (NRVM) were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium‐handling in the presence of control or bisphenol‐supplemented media. A range of environmental and clinically‐relevant exposure levels were tested [10−9 – 10−5M].ResultsAcute BPA exposure (15 – 20 min) altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability beginning at low concentrations (10−8M BPA). BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes and prolonged calcium transient duration time, which replicated our previously published studies in isolated‐whole hearts. BPA‐induced changes in calcium handling increased the propensity for calcium transient alternans, beginning at low BPA concentrations (10−9M). The observed alterations in calcium kinetics following BPA exposure were not the result of cytotoxicity or altered cell viability.ConclusionOur studies show that acute BPA chemical exposure can alter neonatal cardiomyocyte physiology. Additional studies are necessary to determine the effects of bisphenol exposure on pediatric heart electrophysiology and mechanical function, as well as the impact of long‐term treatment that more closely mimics clinical exposure.Support or Funding InformationThis publication was supported by the National Institutes of Health (R00ES023477, UL1TR000075), Children's Research Institute and Children's National Heart Institute.