bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Fads2 Genotype and Dietary Essential Fatty Acid Intake on Metabolic Risk in Mice
Authors: Linde Peter E. , Evans Amanda J. , Li Puma Lance C. , Whitaker Connor M. , Worker Caleb J. , Chicco Adam J. 
Published: June 2021

Polyunsaturated fatty acids (PUFAs) play important roles in inflammation, cardiovascular, and metabolic function. However, controversy exists regarding effects of dietary PUFA intake on metabolic risk due to inconsistent results from studies in the literature. We hypothesized that some of this controversy results from variations in individuals' metabolism of dietary essential PUFAs, suggested by altered cardiometabolic risk profiles in populations with polymorphisms in a key PUFA metabolism gene, FADS2. To address this, we developed colonies of mice with global heterozygous knockout (low), wild‐type (WT; medium) or mild transgenic overexpression (high) of FADS2 expression. Mice were fed a standardized high‐fat (40% kcal) diet containing dietary essential PUFAs at ~7% kcals provided as mostly linoleic acid (18:2n6, LA; as corn oil; 57:1 n6:n3), α‐linolenic acid (18:3n3; as flax oil; 1:4 n6:n3) or a 50/50 blend of each providing 1:1 n6:n3 PUFAs. Effects on glucose tolerance were monitored over 4 months, followed by analysis of liver fat deposition and macrophage content. In mice with WT FADS2 expression, enrichment of a high‐fat diet with n6‐PUFA augmented glucose intolerance, weight gain, and hepatic inflammation; while n3‐PUFA tended to have the opposite effect. The same metabolic syndrome phenotype was augmented by high (transgenic) FADS2 overexpression and attenuated by low FADS2 (knockdown) expression compared to WT controls when dietary n3:n6 PUFA composition was balanced 1:1, demonstrating a potent influence of FADS2 expression on metabolic phenotype and hepatic inflammation. However, dietary imbalance of n3:n6 PUFA intake, either toward higher n3 or n6 PUFA intake, tended to mitigate the effect of higher or low FADS2 expression. Taken together, these results support a complex interaction of FADS2 expression and dietary PUFA intake on metabolic risk, prompting future study of FADS2 haplotypes as potentially relevant criteria for individualized dietary recommendations.Support or Funding InformationThis project is supported by AFRI Grant # 2014‐06594 from the USDA National Institute of Food and Agriculture.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Resuscitation Adjuncts on Indices of Inflammation and Oxidant Stress in Tissues from Swine Subjected to Traumatic Hemorrhage
Authors: Barr Johnny L. , Martini Wenjun Z. , Thomas Theo W. , Dubick Michael A. 
Published: June 2021

IntroductionIn the absence of blood products, pre‐hospitaluse of small volume adjuncts to enhance crystalloid resuscitation has beenproposed to reduce inflammation and improve outcomes in the bleeding traumapatient. However, the most effective drugs for this purpose remain underintense investigation. The present study investigated the effects of Poloxamer‐188(P‐188), a surfactant with membrane resealing activity andethynylestradiol‐3‐sulfate (EE‐3‐S), an estrogen compound, on indices ofinflammation and oxidant stress in tissues from swine subjected to traumatichemorrhage. Both compounds are suggested to have anti‐inflammatory andpotentially anti‐oxidant activity.MethodsThirty anesthetized and instrumented pigs weresubjected to a left leg femur fracture followed by hemorrhage of 55% of the estimatedblood volume and a 15 min shock period. Pigs were then randomized into 3 groups(n=10/group) and resuscitated with equal small total volumes of normal saline (NS;4ml/kg) alone or NS containing P188 (200 mg/kg) or EE‐3‐S (1 mg/kg). Animalswere continuously monitored under anesthesia for 6h or until death. At death oreuthanasia, samples of liver, kidney, lung, heart and jejunum were flash‐frozenand stored at −80°C until assayed for antioxidant status, antioxidantenzyme activities and select cytokines.ResultsHemorrhage reduced mean arterial pressure to 54±6%of baseline levels (p<0.05). In all tissues, total antioxidant status, reduced glutathione and antioxidant enzyme activities were similar amonggroups. In lung, however, nitric oxidelevels were 28% lower in the P‐188 treated than NS group (p<0.05). In liver, levels of IL‐1β, TNF‐α and IL‐6 were 25–30% lower in the P‐188 and EE3‐S treatedthan NS resuscitated swine (p<0.05), whereas IL‐10 levels were similar amonggroups. No statistically significant differences in cytokine concentrationswere observed in kidney, lung, heart or jejunum among the groups.ConclusionsThese data suggest that in this swine model oftraumatic hemorrhage and small volume resuscitation with crystalloid containingP‐188 or EE3‐S, any anti‐inflammatory activity was only observed in the liver.Support or Funding InformationUS Army Institute of Surgical Research, San Antonio, TX 78234This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CB2 Receptor Role in Anxiety‐like Behavior Using Validated CB2‐KO Zebrafish
Authors: Acevedo‐Canabal Agnes , Colon‐Cruz Luis , Varshney Gaurav , Behra Martine , Yudowski Guillermo 
Published: June 2021

More than 100 million people use Marijuana or a synthetic analog worldwide, but effects and side effects are still poorly understood. Most cannabinoids, like Δ9‐tetrahydrocannabinol (Δ9‐THC), the main active constituent of marijuana, modulate the mesocorticolimbic system through binding to two cannabinoid receptors (CBRs) which are present in all vertebrates. The cnr1 and cnr2 genes encode the cannabinoid receptor 1 (CB1) and 2 (CB2), respectively. While CB1 is the most abundant G protein‐coupled receptor (GPCR) in the central nervous system (CNS), CB2 was thought to be primarily expressed in immune cells where it plays a major role in regulating the inflammatory response. However, there is increase evidence for expression and biological roles of CB2 receptor in the CNS. Thus, the goal of our experiments was to identify such role(s) by examining “anxiety‐like” behaviors in larval zebrafish. First, we established CB2‐knockout (CB2‐KO) animals using the CRISPR/Cas9 genome‐editing tool. An allele carrying an early 2bp deletion (cnr22Δ) in the coding sequence resulted in a loss of function mutation that we validated via Western Blots showing that the CB2 protein was absent in the adult homozygote brains (cnr2−/−2D). Next, we used a larval behavioral assay based on the photo‐dependent swimming response (PDR) and measured three anxiety‐like parameters (1) hyper/hypo activity, (2) Center avoidance and (3) photo‐stimulated startle response (PSSR) in wild type and CB2‐KO larvae. We found that all of those “anxiety‐like” behaviors were affected in the animals lacking CB2, thus clearly establishing this receptor as an important modulator of those behaviors.Support or Funding InformationNational Institute of Drug Abuse (R01.DA037924) and the National Science Foundation (HRD.1137725)‐Puerto Rico Center for Environmental Neuroscience (PRCEN).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 Origin of the Avian Head as told by Transformations in the Fossil Record and Embryonic Development
Authors: Bhullar Bhart‐Anjan S. 
Published: June 2021

The head of birds is immediately and profoundly distinguishable from those of other major vertebrate clades, owing to a bewildering number of derived features including an expanded brain and eyes, a shortening of the maxillary face, and an expansion of the premaxillary region at the tip of the snout into the characteristic avian beak. Considered separately, multitudes of individual transformations are required to bridge the gap between an ancestral reptilian cranium and a bird skull. However, in our work, we have found that large‐scale cranial evolution operates in such a way that multiple transformations have a single underlying developmental cause, resulting in character nonindependence and a simpler and more elegant evolutionary story than has previously been assumed. Foremost, we find that the avialan skull is fundamentally a juvenilized or paedomorphic version of the ancestral dinosaurian skull, and that many if not most of the iconic features of birds can be explained using a simple growth or scaling mechanism. In addition, the beak and skull roof — the entire modern avian feeding system, which features a great deal of mobility or kinesis — is patterned by one or a few early developmental influences. Finally, the highly modified avian skull roof is primarily influenced by the transformed brain, and indeed evidence suggests that a tight linkage between these structures is ancestral for Osteichthyes. We also found indications that the expanding brain restricted the size of the jaw‐closing musculature. Remarkably, the fossil record supports many of these hypotheses, showing clear signals of juvenilization and correlated shifts in brain and skull, and also showing simultaneous transformation of the rostral beak and the palate as suggested by our developmental work. We find particular support for our hypotheses using new material of the most important fossil taxa demonstrating the “modernization” of the avian skull, the Cretaceous toothed stem‐birds Ichthyornis and Hesperornis. However, this material simultaneously demonstrates that the avian adductor chamber was, in at least some taxa, remarkably plesiomorphic even after the expansion of the brain, falsifying our hypotheses of a strict causal relationship between brain expansion and adductor diminution. Thus, despite the importance of developmental data in demonstrating the ways in which character transformations are interrelated during major evolutionary transitions, the fossil record is always the final arbiter of the merit of any large‐scale evolutionary hypothesis.Support or Funding InformationFunding provided by Yale University, the Yale Peabody Museum of Natural History, the National Science Foundation, and the Human Frontier Science Foundation.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 Cardioprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) on H2O2‐induced H9c2 Cell Damage Compared to Common Anti‐oxidants
Authors: Lefkowitz Dylan Samuel , Sandhu Robinder , Kim Alissa , Wieczorek Peter , Castellano Andrew , Barsotti Robert , Young Lindon , Chen Qian 
Published: June 2021

Caffeic Acid Phenethyl Ester (CAPE) is a natural compound that has been found to exhibit anti‐proliferative, anti‐inflammative, and anti‐oxidant effects, although these effects have not been fully elucidated on cardiomyocytes. Oxidative stress in the heart contributes to the pathogenesis of various cardiovascular diseases, such as ischemia/reperfusion injury following a myocardial infarction. This study investigated the cardioprotective effects of CAPE against hydrogen peroxide (H2O2)‐induced oxidative injury in rat cardiomyocytes (H9c2) in pre‐treatment (24 hours before H2O2) and co‐treatment (with H2O2), and compared these activities to vitamin C, coenzyme Q10, and caffeic acid. Cell viability was evaluated after co‐treatment and pre‐treatment by a cell counting kit‐8 assay. H2O2 (300 μM to 500 μM) dose dependently decreased cell viability, and 500 μM H2O2‐treated cells (n=4) showed a significantly decreased cell viability of 16 ± 2% compared to control cells (p<0.05). By contrast, co‐treatment (n=5) and pretreatment (n=5) of cells with CAPE (5 to 40 μM) significantly reduced cell damage in a dose dependent manner by 24–29% ± 5–8% (p<0.05). However, co‐treatment and pre‐treatment of caffeic acid (1–40 μM. n=3), vitamin C (100–10,000 μM, n=4), and coenzyme Q10 (0.1–100 μM, n=3) did not show any significant protection on cardiomyocytes against H2O2. These preliminary results suggest CAPE can protect cardiomyocytes against oxidative stress induced by H2O2, which indicate CAPE as a potentially beneficial supplement to maintain cardiovascular health. We plan to investigate the mechanism of action of CAPE in future studies.Support or Funding InformationThis study was supported by the Center for Chronic Disorders of Aging, the Division of Research and the Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Metformin on the AMPK Pathway, Cystogenesis and Metabolomic Biomarkers in ADPKD Kidney Epithelial Cells
Authors: Li Hui , Naser‐Tavakolian Aurash , Huang Polly , Rivera Daniel , Hallows Kenneth R. 
Published: June 2021

Autosomal dominant polycystic kidney disease (ADPKD) is a ciliopathy characterized by the slow and continuous development of cysts derived from renal tubular epithelial cells and is caused by mutations in genes that encode polycystin‐1 (PKD1) and polycystin‐2 (PKD2). Cyst formation and growth results from dysregulated intracellular calcium homeostasis and increased cAMP generation, CFTR activity, and mammalian target of rapamycin (mTOR) pathway signaling. Recent studies in PKD1‐null cells also suggest that there is decreased activity of the metabolic sensor AMP‐activated protein kinase (AMPK) and an excessive reliance on aerobic glycolysis (the ‘Warburg effect’). Here we sought to determine the roles of AMPK and dysregulated metabolism in the pathophysiology of ADPKD, and how the AMPK activator metformin, a potential novel therapeutic for ADPKD, affects these parameters and cyst growth in vitro in both PKD1‐ and PKD2‐null cells. We used immortalized PKD1‐ and PKD2‐null kidney epithelial cells for immunoblotting to measure cell proliferation (mTOR and ERK) and AMPK pathway markers and the levels of key glycolytic enzymes. We also used 3‐D Matrigel cultures to assess cyst growth and Seahorse Extracellular Flux Analyzer assays to evaluate the metabolic phenotype of cells as a function of different treatments. Unlike in PKD1‐null cells, PKD2‐null cells displayed neither excessive activation of the mTOR pathway, inhibition of the AMPK pathway, nor apparent metabolic dysregulation under baseline conditions. Nevertheless, metformin effectively activated AMPK in polarized PKD2‐null cells and significantly inhibited cyst growth in 3‐D cultures, both in the presence and absence of cAMP agonists. PKD1‐null cells had significantly increased cAMP production, with increased expression of the key glycolytic pathway enzymes pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Metformin treatment dose‐dependently inhibited expression of these enzymes and ERK activation in PKD1‐null cells. Seahorse metabolic assays showed that PKD1‐null cells have significantly increased basal and compensatory glycolysis. Metformin inhibited oxidative metabolic flux in both PKD1‐ and PKD2‐null cells. We conclude that cystogenesis may occur through differing signaling pathways depending on mutation in ADPKD. Metformin may thus exert beneficial effects in PKD2 mutant cells by mechanisms distinct from those proposed in PKD1 mutant cells and may be in part AMPK‐independent. Additional studies in primary cells and in vivo will be applied to confirm these immortalized cell results.Support or Funding InformationSupported by NIH‐NIDDK and U.S. Dept. of DefenseThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dairy Exosome Effects on Mitochondria Function and Antioxidant Enzymes in Growing Male and Female Rats
Authors: Parry Hailey A. , Mobley C. Brooks , Mumford Petey W. , Romero Matthew A. , Zhang Yufeng , Zempleni Janos , Young Kaelin C. , Roberts Michael D. , Kavazis Andreas N. 
Published: June 2021

Exosomes facilitate cell‐to‐cell communication by transporting a variety of molecular cargo among tissues, and have been associated in numerous physiological and pathological conditions. Recent data show that exosomes are not only derived from endogenous synthesis, but can also be obtained from dietary sources (e.g., milk). The aim of this study was to assess the effects of milk exosomes on skeletal muscle and liver mitochondria function, reactive oxygen species (ROS) emission, and antioxidant protein levels in young growing rats. Twenty‐eight day old male (n=12) and female (n=12) Fisher 344 rats were used in this study. For four weeks half of male (n=6) and female (n=6) rats were fed a milk‐based diet containing exosomes (EXO+), and the other animals were fed the same diet which was exosome‐depleted (EXO−). Skeletal muscle and liver mitochondria were isolated for respiration and ROS emission assays. Additionally, protein expression of the antioxidants superoxide dismutase 1/2 (SOD1/2), catalase (CAT), and glutathione peroxidase (GPX) were measured via Western blot in skeletal muscle and liver. State 3 skeletal muscle mitochondria respiration exhibited an interaction effect (p=0.039) with males fed the EXO+ diet having the highest respiration rate. State 4 skeletal muscle mitochondria respiration was higher (p=0.047) in male than female rats independent of diet. State 3 liver mitochondria respiration was not significantly different (p>0.05), but state 4 liver mitochondria respiration was higher (p=0.007) in EXO− rats independent of sex. ROS emission from isolated liver mitochondria was lower (p<0.001) in female rats independent of diet, and liver GPX protein levels were higher (p = 0.005) in female rats independent of diet. No significant differences (p>0.05) were observed in skeletal muscle ROS emission or antioxidant protein levels. In conclusion, the depletion of dairy exosomes from the diet affected mitochondrial physiology in skeletal muscle and liver. In addition, our data show that female rats had lower liver ROS emission and higher antioxidant protein levels (i.e., GPX) compared to male rats. These data may support the mitochondrial free radical theory of ageing since female Fisher 344 rats outlive the male counterparts.Support or Funding InformationSupport provided by AU IGP funds to ANK and MDR. JZ is supported by NIH, NIFA, Gerber Foundation and Egg Nutrition Center, and is a consultant for PureTech.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Long Term Hypoxia Reduces Ca2+ Oscillations in Basilar Arterial Myocytes of Fetal and Adult Sheep
Authors: Reid Casey , Romero Monica , Dobyns Abigail , Wilson Christopher G. , Hessinger David A. , Longo Lawrence D. , Zhang Lubo , Wilson Sean M. 
Published: June 2021

Ca2+ oscillations are important in the regulation of many cerebral arterial functions ranging from vasoconstriction to gene transcription. Without these oscillatory waveforms, there are alterations in the signaling pathways regulated by Ca2+. Previous work has shown that long term hypoxia (LTH) due to high altitude exposure can cause cerebral vascular dysfunction including changes in reactivity and morphology in the fetus as well as adult. Studies performed in cerebral arterial preparations have illustrated that LTH in sheep fetus and adult cause whole cell Ca2+ signaling dysfunctions that compromise vascular reactivity and contribute to cerebral arterial pathologies. Based on the premise that Ca2+ oscillations, vasoconstriction, vessel morphology, and LTH mediated cerebral arterial function are interrelated we tested the hypothesis that LTH impairs Ca2+ oscillations. The impact of LTH and maturation on Ca2+ signals in cerebral arterial myocytes was examined using confocal imaging techniques of flou‐4 loaded myocytes of basilar arteries from low (700m) or high altitude (3,801m) near term fetal or adult sheep. LTH decreased the intracellular Ca2+ signals independent of age due to a faster decay in the Ca2+ signal, an effect that could impair vasoconstriction, alter tissue structure, and compromise the regulation of cerebral blood flow. Along with producing smaller Ca2+ events, the data show that LTH inhibits the cell's ability to respond with Ca2+ signals in response to 30 mM potassium‐induced depolarization in fetal as well as adult sheep. LTH and ontogeny may also play interconnected roles in Ca2+ signaling as LTH inhibits distant communication between myocytes in fetal sheep, whereas in adult sheep it stimulates local signaling. These observations illustrate that altitude and maturation each modify Ca2+ signaling behavior in ways that likely impact arterial reactivity and other mechanisms related to the regulation of cerebral blood flow.Support or Funding InformationThis work is supported by The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development grant number HD083132, by the National Science Foundation under Grant No. MRI 0923559, and the Loma Linda University School of Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of Thermoregulatory Capability in Weddell Seal Pups
Authors: Pearson Linnea E. , Weitzner Emma , Whoriskey Sophie , Tomanek Lars , Liwanag Heather E.M. 
Published: June 2021

One of the greatest metabolic costs for endotherms is the energy allocated to thermoregulation. Weddell seals (Leptonychotes weddellii) are the southernmost breeding mammals, and as such are born into one of the most challenging thermal environments on the planet. During their nursing period, Weddell seal pups must develop the capability to survive both on the ice and in the water. Pups also concurrently shift from the use of fur to a reliance on blubber for insulation. This study examined the thermal and energetic costs associated with development and thermoregulation in Weddell seal pups. Metabolic rate (MR) in air was measured longitudinally for 4 pups every 2 weeks, starting at 1 week of age through the transition to independence (7 weeks); MR in water was measured in the same pups beginning at 3 weeks. Additionally, we assessed the molt status of each pup, and estimated body composition (blubber vs. lean mass) based on an elliptical cones model. There was a high degree of individual variability in mass‐specific MR in air in 1 week old pups (5.96–10.87 ml O2 min−1 kg−1), though in general it remained stable or decreased slightly from 1–7 weeks of age. Mass‐specific MR in water declined from 3 weeks to 7 weeks of age for 2 of the 4 pups, and remained stable for 2 pups. The difference between mass‐specific MR in air and in water also decreased from 3 to 7 weeks for 2 pups and remained steady for 2 pups; but by 5 weeks of age the difference between MR in air and in water was marginal for all 4 pups. Timing of the initiation of the molt and molt duration was also variable; two pups had molted patches by 3 weeks of age, and all but 1 pup were fully molted by 7 weeks of age. All pups gained mass from 1 to 5 weeks of age at an average rate of 2.02 ± 0.09 kg day−1 and the proportion of blubber increased from 1–3 weeks (25% to 38% of body mass). Blubber proportion remained steady from 3–5 weeks (38% to 40% of body mass) because pups gained proportionally more lean mass (61% of total mass gained). By 7 weeks, 3 of the 4 pups had weaned and were losing mass. Timing of MR equivalence in air and water did not vary with molt status (amount of lanugo) or with estimated body composition. Overall, these results indicate that Weddell seal pups have developed their thermal capabilities by ~5 weeks of age to protect themselves against increased heat loss in water, independent of the amount of lanugo fur or body composition.Support or Funding InformationThis project was funded by the National Science Foundation, Office of Polar Programs (#1543539).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.