bluuebunny/crossref_metadata_2025_split huggingface dataset:
Western versus Omega‐3 Based Diets Differentially Alter Key Brain Fatty Acid Transport Genes
Authors: Umbaugh David S. , Schaller Megan L. , Harris Matthew P. , Wooten Joshua S. , Sandoval Karin E. , Witt Ken A. 
Published: June 2021

The Western high‐fat diet is associated with poor health outcomes, while omega‐3 fatty acids supplementation has shown to mitigate metabolic imbalances seen with the Western diet. Growing evidence shows diet impacts cerebrovascular and brain health. Understanding of how the percentage and type of fat in the diet affects brain and microvascular expression of fatty acid transport genes remains limited.PURPOSETo elucidate the dietary impact of fat type (lard vs. fish oil) and percentage of fat (10% vs 41%) on metabolic parameters and expression of key genes associated with transport and actions of fatty acids in the brain and microvasculature.METHODS8‐week male C57Bl/6 mice (n = 12/group) were randomized to one of four treatment groups: 10% kcal lard,10% kcal fish (menhaden) oil 41% kcal lard or 41% kcal fish oil ad libitum for 32 weeks. Total plasma cholesterol, LDL, HOMA‐IR, glucose, and triglycerides were measured at the conclusion of the study. Cortical (cerebral cortex) and subcortical (hippocampus, amygdala, thalamus, caudate) brain tissues were harvested and mRNA expression (Mfsd2a, Cd36, ApoE, Abca1, Ppara, Pparg) was measured via RT‐qPCR relative to the 10% lard diet. Mfsd2a protein expression was assessed via Western blot.RESULTSMean total cholesterol, LDL, glucose and HOMA‐IR significantly differed with the type of fat, the percentage of fat, and their interaction. The mean LDL, total cholesterol, glucose and HOMA‐IR were significantly higher in mice receiving 41% lard compared to mice receiving other diets. Mean cortical Mfsd2a protein expression significantly differed with the percentage of fat and the interaction between the type and percentage of fat. Mean Mfsd2a protein expression was significantly higher in all other diet groups compared to 10% lard. Mean cortical Mfsd2a mRNA expression differed with the type of fat. Mice receiving fish oil had higher‐fold Mfsd2a mRNA expression compared to those receiving lard. Mean cortical Pparg mRNA expression significantly differed with the type and percentage of fat. Mice receiving fish oil or 41% fat had higher‐fold Pparg expression compared to mice receiving lard or 10% fat, respectively.CONCLUSIONSFindings showed that the type and percentage of fat could play a critical role in the metabolic profile and expression of genes involved in the transport or action of fatty acids in the cerebrovasculature and/or brain.Support or Funding InformationThis work was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (Grant: R21NS090282).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TNFα Impairs Cerebral Blood Flow Autoregulation in Pregnant Rats
Authors: Duncan Jeremy W. , Warrington J. Paula , Drummond Heather A. , Granger Joey P. , Ryan Michael J. 
Published: June 2021

Neurological symptoms are often reported among preeclamptic patients and cerebrovascular events account for ~40% of all preeclamptic/eclamptic‐related deaths. While cerebral blood flow (CBF) autoregulation is impaired in preeclamptic (PE) women as well as in placental ischemic rats which develop a PE‐like syndrome, the underlying mechanisms responsible for abnormal CBF autoregulation are unclear. Placental ischemic rats have higher levels of circulating cytokines, and we previously reported that tumor necrosis factor – alpha (TNFα), at levels that mimic TNFα in human preeclampsia, increases blood brain barrier (BBB) permeability and cerebral edema in pregnant rats. Therefore, we tested the hypothesis that TNFα alters CBF autoregulation in pregnant rats. To test this hypothesis, normal pregnant Sprague Dawley rats were infused with TNFα (200ng/day) and cerebral blood flow was measured by laser Doppler flowmetry under anesthesia. Rats were intubated and ventilated in order to maintain constant blood gasses and mean arterial pressure was elevated step‐wise from 100–190 mmHg by infusion of phenylephrine to determine changes in CBF. TNFα was found to impair CBF autoregulation in pregnant rats where CBF was significantly increased in TNFα‐infused rats at 180 mmHg (225±13 vs 173±8) and 190 mmHg (253±17 vs 188±9) compared to normal pregnant rats with no significant difference in peak CO2 between the two groups at 180 mmHg (44.9±0.8 vs 45.4±0.9 mmHg) or 190 mmHg (43±0.8 vs 45.3±0.9). Autoregulatory index (percent change in blood flow divided by percent change in perfusion pressure) was also significantly increased in TNFα‐infused rats at 180 mmHg (1.56±0.17 vs 0.91±0.11) and 190 mmHg (1.7±0.07 vs 0.99±0.11) compared to normal pregnant rats. These data suggest that circulating TNFα from the ischemic placenta could contribute to cerebrovascular complications during pregnancy and postpartum. TNFα could serve as a novel pharmacological target to ameliorate CBF autoregulation in preeclampsia.Support or Funding InformationThis study was supported by National Institutes of Health Grants, HLHL51971, HL136684‐A0, and an NRSA Institutional Training Grant, T32HL105324.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of the OVLT‐gut microbiome axis on the development of DOCA‐salt hypertension
Authors: Collister John , Nahey David , Hartson Rochelle , Youmans Bonnie , Johnson Tim 
Published: June 2021

Limited studies suggest an association of gut microbiome changes with certain forms of hypertension, but a cause/effect relationship has yet to be fully defined. The deoxycorticosterone acetate (DOCA)‐salt model of hypertension in rats is known to have a neurogenic component linked to increased sympathetic nervous system activity. Indeed, we have recently shown the hypertensive response in DOCA‐treated rats requires the organum vasculosum of the lamina terminalis (OVLT), a circumventricular organ that has direct connections to the paraventricular nucleus (PVN) to increase sympathetic activity. Furthermore, celiac ganglionectomy also supports a role of splanchnic sympathetic innervation to the gut in the hypertensive response to DOCA. Taken together, we hypothesize an OVLT‐sympathetic‐gut (OSG) microbiome axis is involved in the development of hypertension. Having previously reported that the OVLT plays a significant role in the development of DOCA‐salt hypertension, the present study was designed to test the hypothesis that the OVLT mediates changes in the gut microbiome associated with concomitant hypertension. In uninephrectomized OVLT lesioned (OVLTx; n = 5) and SHAM (n = 2) Sprague‐Dawley rats consuming a 2% NaCl diet and 0.9% NaCl drinking solution, 24‐hour mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg/rat; SQ). Microbiome analyses were performed on regional gut samples at the end of the study and compared to normal rats (n=2). The chronic pressor response to DOCA was attenuated in OVLTx rats such that MAP increased to 153±4 mmHg in SHAM rats by Day 21 of DOCA compared to 127±5 mmHg in OVLTx rats. Moreover, DOCA hypertension in SHAM rats was associated with decreased levels of Lactobacillus species in the jejunum and ileum, and increased Escherichia levels in the cecum compared with normal rats. However, these changes in bacterial genera were mitigated and offset by lesion of the OVLT and these bacterial populations in OVLT lesioned rats with attenuated hypertension more closely resembled those in normal control rats. We conclude that DOCA‐salt hypertension is associated with specific microbiome changes in the gut, and the attenuated hypertensive effects of DOCA‐salt in OVLT lesioned rats is mediated in part through counteracting changes in these bacterial populations.Support or Funding InformationUniversity of Minnesota Grant‐In‐Aid # 107426This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gut Microbiota Effects On Bone Density Are Dependent On T‐ and B‐ lymphocytes
Authors: Rios‐Arce Naiomy Deliz , Schepper Jonathan , McCabe Laura R. , Parameswaran Narayanan 
Published: June 2021

Recent studies have shown that gut microbiota is an important regulator of bone density. In addition, it is well known that the gut microbiota can modulate the immune system. However, whether the effects of the gut microbiota on bone health involve the lymphocytes is still unknown. We hypothesized that modulation of gut microbiota will alter bone density, and this effect will be prevented in the absence of lymphocytes. To test our hypothesis, we treated Rag knockout (T and B lymphocyte deficient) mice and the corresponding C57BL/6J wild‐type mice (males, 12 weeks of age) with antibiotics (ABX) ampicillin (1g/L) and neomycin (0.5g/L) in the water for two weeks. After two weeks, mice received water without antibiotics for another 4 weeks to allow the repopulation of gut microbiota. Bone volume fractions (BVF) of the femur were analyzed using microcomputed tomography system. Fecal samples were used to confirm microbiota depletion after 2 weeks and repopulation after 6 weeks. Repopulation of the gut microbiota in the WT‐ABX group significantly decreased femoral trabecular BVF by 24% compared to the non‐ABX treated WT group (BVF/BW WT:.98, WT‐ABX:.74, n= 14–17). In the Rag KO mice, however, repopulation of the gut microbiota following ABX treatment did not affect femoral BVF compared to the respective control group (BVF/BW KO: 1.59, KO‐ABX: 1.49, n=7–11). Analysis of serum bone remodeling parameters indicated significantly lower serum osteocalcin levels (~ 37% of control levels) in WT‐ABX treated mice, while no changes were seen in the RAG‐KO group. Our study demonstrates that repopulation of the gut microbiota can be detrimental to the bone and that this effect is dependent on the T and B lymphocytes.Support or Funding InformationPorter Fellowship awarded to Naiomy‐Deliz Rios Arce. National Institutes of Health Grants RO1 DK101050 and RO1 AT007695‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alcohol‐Induced Gut Lymphatic Leak Results in Adipocentric Immunometabolic Dysregulation in Female Rats
Authors: Souza‐Smith Flavia M. , Simon Liz , Siggins Robert , Molina Patricia E. 
Published: June 2021

Previously we demonstrated that alcohol induces mesenteric lymphatic vessel (MLV)hyperpermeability, perilymphatic adipose tissue (PLAT) inflammation, and impaired insulin signaling in male rats. MLV play an important role in the trafficking of gut mucosal derived dendritic cells (DC) to mesenteric lymph nodes (MLN). Leakage of DC from MLV has been reported in infectious states. DC promote regulatory T cell (Treg) expansion in adipose tissue and this mechanism has been proposed to be a driver of age‐associated insulin resistance. We hypothesize that alcohol‐induced MLV hyperperemeability results in DC leakage to PLAT and this contributes to immunometabolicdys function in chronic alcohol fed animals. To test this hypothesis, female Fisher 344 rats were randomized to Lieber‐DeCarli liquid diet (36% of calories from alcohol) for 10 weeks or pair‐fed control groups. PLAT, MLN, and peripheral blood lymphocytes (PBL) were isolated for phenotyping by flow cytometry. Alcohol‐fedanimals had increased PLAT Tregs and CD4 T cells and decreased % Tregs in PBLs. These findings suggest that alcohol‐induced lymphatic leakage is associated with DC deviation into PLAT that we speculate mediates Treg expansion and initiatesmetabolic dysregulation. In conjunction with our previous findings, these results support an alcohol‐induced immune cell deviation from the gutlymphnode pathway that promotes PLAT immunometabolic dysregulation and couldpotentially have additional implications on induction of mucosal immunity.Support or Funding InformationSupported by LSUHSC Department of Physiology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of germinated brown rice on the LPS‐induced inflammation in adipocytes
Authors: Park Mi‐Young , Lee Young Min 
Published: June 2021

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti‐obesity and anti‐inflammatory effects. However, the mechanisms underlying the anti‐inflammatory effect of GBR on adipocytes are not fully understood. The aim of this study was to explore the anti‐inflammatory mechanisms of GBR on lipopolysaccharide (LPS)‐stimulated 3T3‐L1 adipocytes. 3T3‐L1 adipocytes were pretreated with GBR extracts (0–20 mg/ml) 1h before LPS stimulation. The mRNA expressions of adipokines and Toll‐like receptor 4 (TLR4) were measured by RT‐PCR. The protein expressions of TLR4‐related molecules were detected by western blotting and nuclear factor‐κB (NF‐κB) activation was measured. Our results showed that GBR extract dose‐dependently inhibited mRNA expressions of LPS‐induced tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and monocyte chemoattractant protein‐1 (MCP‐1). GBR extract was found to inhibit LPS‐induced mRNA expression of TLR4 and protein expressions of both myeloid differentiation factor 88 (MyD88) and TNF receptor‐associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor‐activated kinase (ERK) phosphorylation and NF‐κB activation. These results suggest that GBR extract has the anti‐inflammatory property on LPS‐induced inflammation via inhibiting TLR4 signaling including ERK and NF‐κB signaling pathways in adipocytes. (This research was supported by the Soonchunhyang University Research Fund.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Peripheral blood mitochondrial DNA copy number, a potential marker of non‐alcoholic fatty liver disease?
Authors: Tapia Maria Azucena Pescador , Fragoso‐Bargas Nicolas , Rodríguez‐Ríos Dalia , Lazo‐de‐la‐Vega‐Monroy María Luisa , del Rocío Ibarra‐Reynoso Lorena , Ruíz‐Noa Yeniley , del Carmen Preciado‐Puga Mónica , Velazquez‐Villafaña Marion , Jordan‐Pérez Benjamín , Garnelo‐Cabañes Serafin , García‐Ramírez Juana Rosalba , Lund Gertrud 
Published: June 2021

IntroductionNonalcoholic fatty liver disease (NAFLD) includes a spectrum of histological findings ranging from simple steatosis (SS) to non‐alcoholic steatohepatitis (NASH). Although often considered the hepatic manifestation of metabolic syndrome (MS), longitudinal studies suggest that NAFLD precedes MS. To date, liver biopsy is the most accurate method to differentiate between SS and NASH. However, recent studies indicate an association between mitochondrial DNA (mtDNA) copy number and NAFLD severity in liver biopsies. If a similar association exists in peripheral blood, mtDNA copy number could represent a non‐invasive alternative for differentiating NAFLD disease stages.Given the above, we analyzed whether mtDNA copy number differs in individuals discordant for NAFLD and MS. We also probed for correlations between liver and peripheral blood mtDNA copy number, in addition to associations between NAFLD and mtDNA copy number.ObjectiveTo analyze whether mtDNA copy number is a useful blood‐based marker of NAFLD severity.Materials and methodsCohort = 73 peripheral blood samples and liver biopsies obtained from patients that were operated for gallstones; individuals were separated into 4 groups: controls (n = 27), NAFLD (n = 14), MS (n = 9) and MS + NAFLD (n = 23). NAFLD severity was determined according to the parameters described by Kleiner; mtDNA copy number was determined by semiquantitative PCR.ResultsWe found no significant differences in mtDNA copy number across the four groups analyzed (i.e. control, NAFLD, MS, MS+NAFLD). However, we did find an association between mtDNA copy number and NAFLD severity. In particular, we found that a significant increase in mtDNA copy number in SS relative to control samples, while mtDNA copy number was significantly reduced in NASH relative to SS.ConclusionAkin to the previously published data of mtDNA copy number in liver biopsies of individuals with NAFLD, we uncovered a dynamic relationship between mtDNA copy number and NAFLD severity in peripheral blood samples. This suggests that mtDNA copy number may be a promising blood‐based biomarker for differentiating between SS and NASH. To address this issue, we are currently probing for correlations between liver and peripheral blood mtDNA copy number.Support or Funding InformationMexican National Council for Science and Technology (CONACyT).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Proteomic Analyses of Plant Exosomes
Authors: Özdemir Bihter , Çimen Hüseyin 
Published: June 2021

Extracellular vesicles (EVs) have been identified as high potential vesicles for intercellular communication. Although their physiological roles have not been identified clearly, they are spherical, non‐organelle lipid membrane vesicles. Recent studies show that mammalian EVs contain RNA, proteins, and lipids implicated to be essential for their transfer [1]. EVs have three subgroups, which are apoptotic bodies, ectosomes, and exosomes. Exosome is the smallest EV with 50–100 nm diameter and their content is specific to the originated cell. Exosomes play the critical role in cell‐to‐cell communication and promote cellular activities such as stimulation of immune response, lysosome‐like activities or transfer of the antigens to other cells [2]. They have also a potential for biomarker design and cellular targeting based on their RNA and protein specification [3]. Plant cells are also demonstrated to produce exosomes with limited knowledge [4]. Given the available databases for animal exosomes, there is no database for plant exosomes up to date. We present our initial results for protein contents of plant exosomes to be used for the construction of such a database. In this study, Apium graveolens (Celery) exosomes were characterized by mass spectrometry‐based proteomic analysis. Following exosome isolation by using in‐house generated procedure from celery extract, proteins were precipitated with cold acetone. The peptide fractions obtained with filter‐aided sample preparation (FASP) analyzed with nanoLC‐captivespray‐qTOF‐MS/MS (Thermo Dionex RSLC3000 coupled with Bruker Compact). Data were submitted to MASCOT database against green plants to identify proteins.Support or Funding InformationWe would like to thank Prof. Dr. Fikrettin Şahin, Dr. P. Neslihan Taşlı, Kaan Kırbaş and members of YediPROT laboratory for their contribution to this project. This project was supported by Yeditepe 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.
Hyperinsulinemia‐Induced Changes In Chromatin Acetylation In Triple Negative Breast Cancer
Authors: Senapati Parijat , Cordova Jaime , Ann David K. , Seewaldt Victoria , Schones Dustin E. 
Published: June 2021

Obesity‐associated hyperinsulinemia or insulin‐resistance is considered as a poor prognostic factor for triple negative breast cancer (TNBC), a particularly aggressive breast cancer subtype, constituting about 15–20% of all breast cancers. As a growth factor, insulin can activate the PI3K/AKT/mTOR pathway that is associated with the increased proliferation rate of TNBC cells. While this association has been recognized for some time, the mechanistic role of insulin‐resistance in promoting TNBC remains unclear. mTOR signaling enhances mitochondrial biogenesis and activity thereby potentially increasing acetyl‐CoA precursors; pyruvate and citrate. Acetyl‐CoA, in turn, can be utilized by nuclear acetyltransferases for histone acetylation. We hypothesize that hyperinsulinemia‐induced metabolic changes lead to altered chromatin structure in TNBC through genome‐wide changes in histone acetylation. To test this hypothesis, we used quantitative ChIP‐seq (ChIP‐Rx), RNA‐seq, western blot and immunofluorescence analyses on MDA‐MB‐231 (TNBC) cells treated with insulin. Insulin treatment leads to global increase in chromatin‐associated histone acetylation levels, particularly at H3K9. Using inhibitors targeting kinases in the PI3K/AKT/mTOR signaling pathway, we demonstrate its role in insulin‐induced histone hyperacetylation. ChIP‐Rx confirmed the global increase in histone acetylation at gene promoters that could potentially alter chromatin accessibility and/or gene expression. Comparison of ChIP‐seq and RNA‐seq data revealed that insulin upregulated genes accumulate higher levels of H3K9ac as compared to downregulated genes after insulin treatment. In addition, insulin induces higher levels of reactive oxygen species and DNA damage foci in cells. Moreover, peripheral blood mononuclear cells from insulin‐resistant women show higher levels of H3K9ac and DNA damage marker gamma‐H2AX relative to those from insulin‐sensitive women. These results demonstrate the significance of targeting hyperinsulinemia‐induced processes that lead to chromatin dysfunction through mitochondria in TNBC.Support or Funding InformationThis work was supported by the NCI (R01 CA220693) and a City of Hope CCSG pilot award.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antibiotic Suceptibility Studies and Protein Degradation by Fungi Growing in Aerobic and Anaerobic Conditions
Authors: Mercado Benjamin , Bayman Paul 
Published: June 2021

Fusarium species cause a broad spectrum of infections including superficial infections in healthy people or disseminated infections in immunocompromised patients. Many of these infections have been associated with proteases secreted by fungi to degrade keratin, an important component of the skin and other tissues. Ischemia and abscess are complications associated to the lack of oxygen in severe mycosis caused by Fusarium. However studies of protein degradation by fungi have been done only in aerobic condition. In this study we hypothesized that protease production would be greater in anaerobic than in aerobic condition. 14 Fusarium isolated from environmental samples were grown in Gelatin Media enriched with sodium nitrate to compare their ability to degrade proteins in anaerobic vs. aerobic conditions. Also antibiotic susceptibility was tested using Fluconazole, Itraconazole and Myconazole in aerobic and anaerobic conditions. All fungi tested showed higher Hydrolysis Capacity Index under anaerobic conditions. In aerobic conditions almost all the fungi tested showed similar colony sizes and halo of protein degradation. On other hand, under anaerobic conditions smallest colony sizes exhibited greater halos of protein degradation. Similarly, all fungi tested were more susceptible to antibiotics in anaerobic conditions too. This study showed high protein degradation in anaerobic conditions. Usually fungal contribution to degradation is ignored due to their low presence in environmental or clinical samples under anaerobic conditions. Our results suggest that Fusarium population could have a role or an impact in anaerobic environments such as ischemia or abscess where protein degradation takes place. Future works includes identification of proteins secreted under anaerobic conditions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.