bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Carotid Body in Doxorubicin‐induced Heart Failure
Authors: Arnold Alexandre José Tavolari , Jensen Leonardo , Souza Leandro E. , Silva Maikon B. , Santos Fernando , Moraes‐Silva Ivana C. , Irigoyen Maria‐Claudia 
Published: June 2021

Doxorubicin (DOX) cardiotoxic effects may lead to heart failure, a condition of high morbidity and mortality characterized by a marked sympathetic hyperactivity. Currently, evidences show that carotid corpuscle (CC) denervation can be a therapeutic approach in cardiac diseases due to the possibility of reducing this sympathetic overactivity. Therefore, we aimed to investigate whether CC denervation can attenuate autonomic and cardiac dysfunctions induced by DOX in rats.MethodsAfter ethical committee approval (4412/16/07), male Wistar rats were divided in: Control (C; n=11), DOX (D; n=5) and DOX+CC denervation (DD; n=7). DOX was administered 6 times by i.p. injections every 4 days reaching a total dose of 2.5mg/kg. After 10 days of the last dose of DOX, the animals were evaluated by echocardiogram and prepared for the recording of direct blood pressure signals. Autonomic modulation was studied by spectral analysis. Results are expressed as mean±SEM; p <0.05.ResultsBoth D and DD rats presented heart rate increase vs. C (C=312 ± 3.6; D=408 ± 16.5; DD=430 ± 25.6 bpm) without blood pressure changes. Elevated sympathetic modulation was confirmed in both D and DD rats vs. C by the increase in the LF (low frequency) component of heart rate (C = 14.27 2.0; D=32.50 ± 2.6; DD=27.7±2.7 n.u.), and an increase in sympathovagal balance (C=0.19±0.03; D=0.53±0.07; DD=0.42±0.07). Reduction in the vagal modulation, expressed by the HF (high frequency) component, was also seen in DD and D rats (C=85,7±2.0; D=67.5±2.6; DD=72.29 ± 2.7 n.u.) together with a decrease in baroreflex gain higher than 50% in these groups vs. C. D and DD groups reduced diastolic left ventricle diameter (C=9.22±0.4 mm; D=8.93±0.2 mm; DD=7.96±0.2 mm) and volume (C=710.6 ± 2.0; D=378.01 ± 1.5; DD=407.13 ± 16.00 uL). Diastolic dysfunction in DD group was evidenced by the increase in isovolumetric relaxation time (C=22.27±1.61; D=23.25±1.47; DD=30.64±1.78 ms) and E/E′ relation (C=13.0 ± 2.3; D=15.19 ± 2,0; DD=34.83 ± 2.19), and by the decrease in E′/A′ ratio in both D and DD groups (C=1.64±0.1; D=0.73±0.1; DD=0.54±0.05). DD also presented systolic dysfunction in relation to C and D rats, evidenced by a decrease in both ejection fraction (C=79.19±3.35; D=76.55±6.95; DD=53.90±3.35 %) and fractional area change (C=62.03±5.5; D=57.45±2.5; DD=43.18±3.6 %).ConclusionCC denervation did not alter the autonomic dysfunction induced by DOX; however, it was more deleterious to cardiac function. In this early phase (10 days) of DOX‐induced heart failure time course, sympathetic modulation may compensate the cardiac maldaptations, thus CC integrity played a key role.Support or Funding InformationCNPq 467300/2014‐3This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence for a circulating factor released by the brain that contributes to chronic antidiabetic actions of leptin
Authors: do Carmo Jussara M. , da Silva Alexandre A. , Hall John E. 
Published: June 2021

We previously demonstrated that leptin has powerful central nervous system (CNS)‐mediated antidiabetic actions that are independent of the autonomic nervous system (ANS) and the pituitary. In this study, we examined if a circulating factor released by the brain contributes to leptin's chronic antidiabetic actions in insulin deficient rats. Male inbred 4‐week‐old Lewis rats (n=14) were conjoined by attaching their skin to allow shared circulation. Six weeks later, the rats were implanted with an intracerebroventricular (ICV) cannula into the lateral ventricle to infuse leptin in one rat and vehicle in the other rat of each pair. Eight days after surgery, food intake, body weight and blood glucose concentration were measured for 5 consecutive days and then streptozotocin (STZ) was injected (40 mg/kg) to induce insulin‐deficient diabetes in both rats. Five days after STZ injection, leptin (15 mg/day) or vehicle (0.5 ml/h) was delivered ICV continuously for 7 days via osmotic minipumps. STZ injection significantly increased average blood glucose concentration (359±19 vs. 79±6 mg/dL) and food intake (49±2 vs. 39±3 g/day). Despite higher food intake, average body weight decreased after STZ injection (619±23 vs. 664±23 g). Chronic ICV leptin infusion restored normoglycemia (110±31 vs. 359±19 mg/dL) in leptin‐treated rats and reduced blood glucose by ~27% in the paired parabiotic rat infused with vehicle (269±20 vs. 366±41 mg/dL). Leptin treatment did not reduce food intake (53±20 vs. 49±23 g/day) or body weight (619±23 vs. 610±20 g) in the paired rats. After stopping leptin treatment, blood glucose concentration returned to diabetic values in leptin‐treated (305±44 vs. 110±31 mg/dL) as well as in vehicle‐treated rats (330±11 vs. 269±20 mg/dL), and food intake increased 37% (67±5 vs. 49±3 g/day). These results suggest that the chronic antidiabetic effects of leptin may involve release into the systemic circulation of a brain‐derived neuroendocrine factor that enhances glucose homeostasis in insulin deficient rats. (NHLBI‐PO1HL51971, NIGMS P20GM104357)Support or Funding InformationDepartment of Physiology and Biophysics and Mississippi Center for Obesity Research. University of Mississippi Medical Center.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cats increase lean body mass with carnitine or carnosine but not with the combination
Authors: Jewell Dennis E. , Panickar KIran S. 
Published: June 2021

This study evaluated whether dietary carnitine or carnosine would change lean body mass, circulating cytokines or metabolites in cats. All study protocols were reviewed and approved by the Institutional Animal Care and Use Committee, Hill's Pet Nutrition, Inc., Topeka, KS. Forty four pets were assigned into four groups: Group 1 (n=11) was fed the control diet, group 2 (n=11) was fed the control diet + L‐carnitine (0.03%), group 3 (n=12) was fed the control diet + L‐carnosine (0.1%), and Group 4 (n=10) was fed the Control diet + L‐carnitine + L‐carnosine. The ages of the cats ranged from 7.2 to 13.9 yr. The duration of the study was 6 months. Initial body composition, cytokines and metabolomics profiles were compared to final and changes were compared across treatments. Metabolomics were measured by Metabolon (Morrisville, NC), cytokines were measured by ELISA. Change in lean body mass (LBM) was assessed by Dual‐energy X‐ray absorptiometry (DEXA) and reported in cats as the difference in LBM between initial and final times. Changes in analytes were then compared amongst the 4 groups. Serum levels of cytokines assessed included Flt‐3L, IFN‐γ, IL12p40, IL‐4, IL‐6, IL‐8, IL‐13, IL‐18, and MCP‐1. Modest reductions were observed in the levels of selected cytokines on day 169 when compared to the baseline but these changes were not significant between groups. Lean body mass results showed that cats fed either carnitine alone (+106 g) or carnosine alone (+96 g) had increased lean when compared to control cats or cats supplemented with both carnitine and carnosine (p<0.01). There was no statistical difference between treatments in either body weight or body fat change. Carnitine and deoxycarnitine were increased in the group that had carnitine alone (p<0.05) while many acyl carnitines were increased in both groups supplemented with carnitine. Carnosine was not changed but beta‐alanine was increased in cats fed carnosine. The metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan and dietary polyphenolic compounds) occurs, in part, through the involvement of enzymes encoded within the microbiome. Several microbiota‐derived‐metabolites were higher in Groups 2, 3, and 4 when compared to Group 1 at various time points. These data indicate that supplementation of carnitine or carnosine is beneficial in increasing LBM in felines but that when combined they do not influence LBM.Support or Funding InformationThis study was funded by Hill's Pet Nutrition Inc.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hydroxylated Metabolites of Common Airborne Polychlorinated Biphenyls and Their Potential for Disrupting Estrogen Homeostasis and Adipogenesis
Authors: Parker Victoria S. , Squirewell Edwin , Joachim‐Lehmler Hans , Robertson Larry W. , Klingelhutz Aloysius , Duffel Michael W. 
Published: June 2021

Endocrine disruption, metabolic syndrome, diabetes, cancer, and other diseases have been associated with exposure to polychlorinated biphenyls. There is a growing interest in the lower chlorinated PCBs due to their presence in the indoor air of older buildings, their susceptibility to metabolism catalyzed by cytochrome P450 to form hydroxylated PCBs (OH‐PCBs), and their potential to disrupt endocrine function. OH‐PCBs are further metabolized in reactions catalyzed by cytosolic sulfotransferases (SULTs) to form PCB‐sulfates. Estrogen sulfotransferase (SULT1E1) is important in the regulation of cellular levels of active and inactive estrogens, with estradiol being a primary physiological substrate. Recent literature has suggested that decreased activity of SULT1E1 can impact adipocyte differentiation. We hypothesize that some lower‐chlorinated OH‐PCBs potently inhibit SULT1E1 causing increased cellular levels of estradiol and a decrease in human adipocyte differentiation. Our studies using purified recombinant human SULT1E1 (at 7.0 nM estradiol) found 4‐OH‐PCB 11 and 4′‐OH‐PCB 25 to be potent inhibitors, with IC50 values of 7.2 and 7.3 nM, respectively. 4′‐OH‐PCB 8 and 4‐OH PCB 52 inhibited SULT1E1 with IC50 values of 17.6 and 18.6 nM, respectively, and the least potent inhibitor, 4′‐OH‐PCB 3, had an IC50 of 1300 nM. We have exposed immortalized human adipocytes to these five OH‐PCBs and another known inhibitor of SULT1E1, triclosan, at concentrations of 1 uM and 10 uM for 72 hours followed by differentiation for 11 days. The cells were stained with AdipoRed to quantitate lipid accumulation. Exposure to 4′‐OH‐PCB 3 resulted in no significant reduction in lipid accumulation, while the remaining OH‐PCBs and triclosan showed significant reductions in adipocyte differentiation. This congener‐selective ability to inhibit SULT1E1 and adipocyte differentiation is consistent with the hypothesis that OH‐PCB‐mediated inhibition of SULT1E1 can inhibit human adipogenesis. Future studies will explore the role of this inhibition of SULT1E1 in adipogenesis by measuring mRNA expression of SULT1E1 and prominent adipogenic markers in these cells as well as cellular levels of estradiol and estradiol‐sulfate.Support or Funding InformationSupported by NIH grants P42 ES013661 and R25 GM058939, and a William Townsend Porter Fellowship from the American Physiological Society.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The role of ACE2/Ang 1–7/Mas axis in the white adipose tissue for the prevention of obesity and insulin resistance through aerobic exercise training
Authors: Américo Anna Laura Viacava , Muller Cynthia Rodrigues , Fonseca‐Alaniz Miriam Helena , Evangelista Fabiana Sant'Anna 
Published: June 2021

The activation of angiotensin converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang 1–7)/receptor Mas axis has been associated with cardiovascular and metabolic improvement, and may represent a new therapeutic target for cardiometabolic diseases. Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). In the present study we evaluated if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1–7)/Mas axis in the white adipose tissue (WAT). Adult male C57BL6/J mice were assigned into chow‐fed controls (C, n=5), chow‐fed trained (T, n=5), cafeteria diet (CAF, n=5), and cafeteria diet plus trained (CAFT, n=5). AET was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (#002/15). The body weight of the T and CAFT groups were lower from the third week of experimental protocol compared to C. The CAF group had higher retroperitoneal and subcutaneous (SC) fat pads weights compared to C, but the AET was able to prevent these increases in the CAFT group. Periepididimal (PE) fat pad weight was lower in T group compared to other groups. Cafeteria diet induced glucose intolerance and IR in CAF group (AUC: 35200± 1076 mg/dL/120 min; kITT: 2.5 ± 0.17 %/min) compared to the C group (AUC: 28333±1305 mg/dL/120 min; kITT: 3.7 ± 0.21 %/min), which were counteracted by AET in CAFT group (AUC: 28896 ± 1133 mg/dL/120 min; kITT: 3.9 ± 0.33 %/min). In the PE‐WAT, the activity of ACE2 was higher in CAF and CAFT groups compared to C and T groups, but Ang 1–7 concentration and Mas protein expression were not different among groups. In the SC‐WAT, no differences were found in ACE2 activity and Mas protein expression, but the Ang 1–7 concentration was lower in CAF and CAFT compared to C and T groups. In conclusion, the prevention of obesity and IR by AET was independent of the ACE2/Ang 1–7/Mas axis activation in the visceral and subcutaneous WAT.Support or Funding InformationSupport: FAPESP #2015/04948‐4; #2016/23783‐9.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Apple Pomace Supplementation Favorably Alters Hepatic Lipid Metabolism in Young Female Sprague‐Dawley Rats fed a Western Diet
Authors: Skinner Roy Christopher , Warren Derek C. , Lateef Soofia N. , Benedito Vagner A. , Bryner Randall W. , Tou Janet C. 
Published: June 2021

Apple pomace is a waste byproduct of apple processing that is high in nutrients including polyphenols, pectin, insoluble fibers, and fructose that may contribute to alleviation of some metabolic diseases. Non‐alcoholic fatty liver disease is the most common chronic liver disease in Western countries with the cause attributed to a high fat, high sucrose (Western diet) consumption. The objective of this study was to determine the effects of apple pomace supplementation on hepatic lipid metabolism. Growing (age 22–29 days) female Sprague‐Dawley rats were randomly assigned (n=8 rats/group) to consume a standard purified rodent diet (AIN‐93G), AIN‐93G +10% kcal apple pomace, Western diet (45% fat, 33% sucrose), or Western + 10% kcal apple pomace diets for 8 weeks. Histological evaluation showed rats consuming Western diets had the highest hepatic steatosis although apple pomace supplementation diet led to a lower degree of fat infiltration. Gene expression of hepatic lipogenesis by RT‐qPCR showed no significant differences of transcription factors, carbohydrate response element binding protein (ChREBP) and sterol element binding protein‐1c (SREBP‐1c), or the enzymes, fatty acid synthase (FAS) and stearoyl‐CoA desasturase‐1 (SCD‐1) among diet treatments. Rats fed Western diet had higher (p<0.01) gene expression of diacylglycerol O‐acyltransferase 2 (DGAT2) than Western + 10% apple pomace. The results suggest lower triacylglycerol synthesis reduced hepatic fat infiltration in rats fed Western diet + 10% apple pomace. In a hypercaloric state, apple pomace supplementation, attenuated hepatic steatosis induced by the consumption of a Western diet, despite the high levels of fructose in this supplement.Support or Funding InformationThis project was supported by Dean Daniel J. Robison, West Virginia University Davis College of Agriculture, Natural Resources, and Design and the West Virginia University Office of the Provost Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The role of butyrate in ethanol‐induced intestinal immune responses and associated gut‐liver injury
Authors: Cresci Gail A.M. , Glueck Bryan 
Published: June 2021

PurposeFollowing a physiologic insult, an immune response needs to be adequately mounted and resolved for proper organ function homeostasis. The immune response to ethanol exposure differs based on multiple factors including the duration of ethanol exposure. While chronic ethanol exposure is proinflammatory, acute ethanol can dampen immune responses. Butyrate, a fermentation byproduct of the gut microbiota, influences gut inflammation and immunity. Our prior work reveals butyrate protects against EtOH‐induced intestinal and hepatic injury. This study aimed to determine butyrate's impact on intestinal innate immune responses following chronic‐binge EtOH exposure.MethodsFemale C57BL/6J age‐matched mice were adapted to a control liquid diet for 5 days, then randomly assigned to a 5% v/v (27% total kcal) ethanol‐containing diet or an isocalorically‐substituted maltose dextrin containing diet for EtOH for 10 days. Ethanol‐fed groups were allowed free access to the diet and control mice were pair‐fed. On day 11, mice were orally gavaged a 5 g/kg dose of EtOH or isocaloric maltose and mice were euthanized 9 hours later. Mice were provided equimolar glycerol or tributyrin (5mM) as part of the liquid diet over the 10 days of EtOH exposure as well as added into the EtOH or maltose gavage at a dose of 2.5 mM. Proximal colon was dissected and mRNA and protein expression of markers of immune and inflammatory response and neovasculature were evaluated.ResultsIn response to chronic‐binge EtOH exposure, genes and proteins for immune and inflammatory mediators had decreased expression in proximal colon including markers for leukocytes, macrophages, neutrophils, cytokines and chemokines. Interestingly, EtOH exposure was also associated with decreased mediators of angiogenesis and markers of vasculature. However, mice co‐treated with tributyrin during EtOH exposure had comparable mRNA and protein expression of several key immune and inflammatory parameters and enhanced makers of angiogenesis as pair‐fed control mice. These preserved responses were associated with protection of intestinal tight junction proteins and liver injury.ConclusionThese findings show tributyrin protected against reduced vasculature and blunted immune responses in the proximal colon caused by chronic‐binge ethanol exposure. These data suggest butyrate could be a potential protective supplement to ethanol consumption and future studies investigating role in human models is warranted.Support or Funding InformationNIH NIAAA R00 ‐ 4R00AA023266‐03This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ursolic acid potentiates paclitaxel induced antitumor effects on esophageal squamous cell carcinoma cell through the Akt signaling pathway
Authors: Meng Ruo Yu , Kim Soo Mi 
Published: June 2021

Development of chemoresistance, poor prognosis, and metastasis often renders the current treatments for esophageal cancer ineffective. The present research is designed to investigate ursolic acid (UA), a component of numerous medicinal plants, either alone or in combination with paclitaxel can inhibit the growth of esophageal squamous cell carcinoma (ESCC) through the Akt/FOXM1 signaling pathway. UA plus paclitaxel treatment inhibited the proliferation of TE‐12 and TE‐8 cells in a dose‐dependent manner when compared to treatment with UA or paclitaxel alone. In colony formation assay, UA potentiated the inhibition of colony formation by paclitaxel when compared to treatment with a single agent. Combination treatment induced apoptosis by increased levels of cleaved poly ADP‐ribose polymerase (PARP) and cleaved caspase‐9 protein and inhibited the invasion and metastasis of ESCC cells. In cell cycle analysis, UA plus paclitaxel induced the G1 cell cycle arrest when compared to treatment with UA or paclitaxel alone. In addition, UA potentiated paclitaxel‐induced inhibition of Akt function and increased phosphorylation form of Akt. These results suggest that UA effectively potentiates the efficacy of chemotherapeutic agents such as paclitaxel via inhibition of proliferation and increased apoptosis by inactivation of Akt in ESCC cells. Taken together, UA enhances the therapeutic efficacy of paclitaxel in esophageal cancer and is a potential clinical anticancer agent for the prevention and/or treatment of ESCC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exposure to a reduced ambient temperature induces browning of bone marrow derived adipocytes in vitro
Authors: Symonds Michael , Velickovic K , Lugo‐Leija H A. , Bloor Ian , Law James , Sacks H , Sottile Virginie 
Published: June 2021

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP) 1 for which the primary stimulus in vivo is cold exposure. The ability to promote the abundance of UCP1 can have a beneficial effect on energy balance as well as lipid and carbohydrate metabolism and as such is a potential anti‐diabesity target. This process has not been studied widely in vitro, for which the impact of modulation of the thermal environment is not well established. The aim of our study was therefore to examine whether cold‐induced UCP1 activation can be achieved in vitro.We thus report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC) of both human and mouse origin. It relies on differentiation at a cool ambient temperature of 32°C instead of the standard temperature of 37°C. The low temperature promoted browning in MSC‐derived adipogenic cultures, with increased adipocyte number (including multilocular cells), and upregulation of adipogenic and thermogenic factors, especially UCP1. Lipid droplets were smaller and more numerous. The bioenergetic status of cells was then investigated using a Seahorse XF96 flux analyser, and the overall respiratory responses calculated for the six key regulators of mitochondrial function. Cells differentiated at 32°C exhibited enhanced uncoupled respiration and metabolic adaptation, with intensified oxidative and glycolytic pathways. Cold‐exposed differentiated cells showed a marked translocation of regulatory hormones to adipocyte nuclei, suggesting a previously unknown role in the browning process. To further determine whether this adipogenic phenotype acquired at 32°C may be reversible as found in vivo, cells differentiated at 32°C were subsequently transferred to standard culture conditions (37°C). This showed that cells transferred from 32°C to 37°C showed a pattern of UCP1 expression similar to that of cells differentiated at 32°C i.e. they retained their beige‐like characteristics.Taken together these results indicate that BM‐MSC can be driven to forming beige‐like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will now provide a powerful tool to further elucidate the regulation of UCP1 function in order to provide a better understanding of the endocrine regulation of the browning process in human adipocytes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.