bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Fat Diet Consumption and its Association with Parenchymal Arteriole Structure and Cognition
Authors: Abolibdeh Bana , Laimon‐Thomson Erinn , Ahmad Amna , Diaz‐Otero Janice M. , Jackson William F. , Dorrance Anne M. 
Published: June 2021

Obesity has been identified as a major risk factor for the development of vascular cognitive impairment with dementia, which is a form of dementia with a vascular origin. Early onset obesity increases the risk of cognitive impairment and sets individuals on a path of cognitive decline that is associated with cerebral hypoperfusion. The parenchymal arterioles (PAs) link the pial arteries to the microcirculation and they form a bottleneck in the perfusion of the microcirculation. Alterations in the structure of PAs could reduce cerebral blood flow and lead to cognitive decline. In this study, we hypothesized that a high fat (HF) diet would lead to a decline in cognition and inward remodeling of PAs. 3‐week‐old male and female Sprague Dawley rats were fed a HF or control diet for 21 weeks. Data are presented as the mean ± SEM, HF vs Control, n=3–4 in each group. At euthanasia, the HF groups weighed more than the controls (Male: 577 ± 68.9vs 450.8 ±18.8g, p=0.0637, Female: 301.3 ±12.0vs 257.3 ± 15.9g, p=0.0351). The HF fed rats had significantly higher abdominal fat weight in both males and females (Male: 20.3± 4.79 vs 7.02 ±1.32g, p<0.05, Females: 11.5 ± 2.02vs 4.05±1.31g, p<0.05). The HF males had significantly elevated fasting blood glucose of 188± 10.8 vs 150.3 ± 8.8mmol/l, p=0.0348while blood glucose was unchanged in the females; 134.5 ± 11.87 vs 129.5 ± 14.5mmol/l, p=0.750. PAs were collected and their structure was assessed using pressure myography under Ca+2free conditions and zero flow. The change in outer, lumen diameter and wall thickness of PAs from HF rats was expressed as a % of the control. In males, a decrease of 35.3± 5.1% in the outer diameter, a decrease of 24 ± 10.3% in the lumen diameter, and a decrease of 58.5 ± 5.9% in the wall thickness was observed. In the females, a decrease of 26.4 ± 8.1% in the outer diameter, a decrease of 36.2 ± 7.8% in the lumen diameter, and an increase of 25± 20% in wall thickness was observed. Cognitive function was assessed using the novel object recognition test. There was no significant difference observed in the % novel object exploration in either group (Male: 36.7 ± 6.34 vs 32.4 ± 1.63%, p=0.0792, Females: 44.8 ± 4.28 vs 45.4 ± 4.35%, p=0.968). Preliminary studies suggest that HF diet alters PA structure without affecting cognition. Interestingly, a sex difference was observed in the effects of HF feeding on wall thickness which was reduced in males and increased in females. This suggests the mechanisms responsible for artery remodeling may differ between sexes.Support or Funding InformationR01‐HL‐137694‐01T32: 5T32GM092715‐08This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of HMGB1 Protein in Experimental Myocardial Infarction
Authors: Cebova Martina , Barta Andrej , Kosutova Michaela , Pechanova Olga 
Published: June 2021

IntroductionMyocardial infarction (MI) results from a reduction in coronary blood flow which is extensive enough to render the oxygen supply to myocardial tissues insufficient. MI remains a leading cause of morbidity and mortality among all cardiovascular diseases over the world. High mobility group box 1 (HMGB1) is a non‐histone chromosomal protein with multiple cardioprotective effects. The aim of the study was to evaluate the effects of HMGB1 protein on biochemical and morphological parameters after experimental MI.Methods12‐week‐old male WKY rats used for the study were divided into following groups: shame operated WKY without MI, WKY with MI, WKY + IM+ anti‐HMGB1 protein. In vivo model of experimental MI was induced by ligation of the left descending coronary artery and lasted 20 min. Before reperfusion anti‐HMGB1 protein was administrated i.v. Animals survived 7 days after MI. Nitric oxide synthase (NOS) activity was determined by conversion of 3[H] Arginine to 3[H] Citrulline in the aorta and ischemic, border and non‐ischemic region of the heart. NFκB expression was determined by Western blot. For morphological parameters, the hearts were excised and used for TTC‐staining procedure. Cytokine levels were investigated using the Bio‐Plex Pro Cytokine kit in the plasma. Concentration of CD was measured spectrophotometrically.ResultsAnti‐HMGB1 protein increased NOS activity in both ischemic and border part of the heart, as well as in the aorta, on the other hand NOS activity did not change in non‐ischemic part of the heart. The protein administration significantly decreased NFκB expression in MI part of the heart, as well as TNF‐alpha and IL‐6 level in plasma. Simultaneously, anti HMGB1 protein decreased MI part as well as border region of the heart.DiscussionConsidering the results, HMGB1 protein is a promising molecule for reduction the negative effects of the myocardium infarction, as well as a promising agent for the treatment of cardiovascular diseases.Support or Funding InformationSupported by: VEGA 2/0170/17, APVV‐14‐0932This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aortic Stiffness Increases More in the Abdominal Than the Thoracic Aorta in Aging Female Monkeys
Authors: Babici Denis , Kudej Raymond , McNulty Tara McNulty , Zhang Jie , Vatner Dorothy , Vatner Stephen 
Published: June 2021

Most experimental studies on vascular stiffness in aging females have been conducted in rodents. However, the lifespan of rodents is only 2–3 years, limiting clinical relevance to humans, and they do not go through menopause, making it difficult to translate the data to aging women. The hypothesis of this investigation was that this topic would be more relevant in aging non‐human primates, as their lifespan is over 30 years and they do go through menopause. Accordingly, the goal of this investigation was to compare aortic stiffness in young adult (6±1 years old) and old (24±1 years old) female macaques. An additional unique feature was chronically implanting aortic pressure and diameter transducers to permit the study of direct and continuous measurements of aortic stiffness in conscious monkeys after full recovery from surgery. Another unique feature was to examine aortic stiffness in both the thoracic aorta (TA) and the abdominal aorta (AA). Aortic stiffness (β) was calculated as systolic pressure/diastolic pressure)/aortic strain. Aortic stiffness increased more, p<0.05, in both the TA (49%) and AA (71%) in old vs young female monkeys. The greatest increases in aortic stiffness in the old female monkeys was in the AA, as reflected by a 42% greater increase in the AA than the TA. These differences were confirmed histologically measuring collagen and elastin density and disarray. Whereas collagen density increased and elastin density decreased more in old vs young monkeys, the greatest differences were observed in collagen and elastin disarray. For example, elastin disarray increased more in the AA than the TA, and more in old vs young monkeys, e.g., there was a 48% greater increase, p<0.05, in the TA elastin disarray in old vs young monkeys. Thus, aortic stiffness increases more in old vs young females, with larger increases in the abdominal vs the thoracic aorta, with the mechanism involving changes in collagen and elastin density, but more importantly, increases in collagen and elastin disarray.Support or Funding InformationFunding information: NIH R01 HL102472This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intact DNA Repair in Differentiated Cardiomyocytes is Essential for Maintaining Cardiac Function in Response to Physiological Stimulus
Authors: de Boer Martine , te Lintel Hekkert Maaike , Krabbendam‐Peters Ilona , Blonden Lau A. , Hoeijmakers Jan H.J. , Duncker Dirk J. 
Published: June 2021

IntroductionDNA in every cell is continuously damaged and DNA repair mechanisms are essential for protection against DNA damage‐induced aging‐related diseases. Evidence indicates that DNA damage is associated with heart failure. We have shown that unrepaired endogenously generated DNA damage drives the early onset of progressive heart failure (de Boer et al. Cardiovasc Res, 2018;114:S105). Here we studied the effects of a physiological stimulus on cardiac function in a mouse model with deficient DNA repair.MethodsTo increase the burden of spontaneous DNA damage, we generated mice with cardiomyocyte‐restricted inactivation of DNA repair endonuclease XPG (αMHC‐Xpgc/−). To induce physiological left ventricular (LV) hypertrophy, mice were exposed to 11 weeks of voluntary wheel running. Subsequently, LV geometry, function and structure were studied at age 16 weeks.ResultsCardiomyocyte‐restricted inactivation of Xpg resulted in systolic as well as diastolic LV dysfunction, demonstrated by decreases in fractional shortening, LVdP/dtP40 and LVdP/dtmin and increases in LV end‐diastolic lumen diameter (LVEDD) and relaxation time constant tau compared to WT (Table). In addition, expression level of hypertrophy maker gene β‐myosin heavy chain (β‐MHC) was elevated. Physical activity has been shown to be beneficial for maintaining and improving cardiac function in mice after myocardial infarction (de Waard et al. Circ Res, 2007;100:1097). In contrast, exercise failed to ameliorate LV remodeling and dysfunction in αMHC‐Xpgc/−, as it produced further increases in LVEDD, tau and β‐MHC compared to sedentary αMHC‐Xpgc/− (Table). Moreover, myocardial collagen content and the number of γH2A. X positive nuclei, a marker for DNA damage, were increased, suggesting that αMHC‐Xpgc/− showed increased susceptibility to exercise.ConclusionCardiomyocyte‐restricted loss of DNA repair protein Xpg increases cardiac vulnerability to develop heart failure in response to exercise training. These findings underscore the importance of genomic stability for maintenance of cardiac function, not only during basal conditions, but also in response to a physiological stimulus.Support or Funding InformationSupported by a NHF Grant 2007B024 and CVON‐ARENA (CVON2011‐11).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Cocoa Flavanols and Metabolites on β‐cell Proliferation and Survival
Authors: Austin Matthew C. , Smyth Brooke J. , Manwaring Lauren P. , López G. Moroni , Ross Mimi T. , Tessem Jeffery Sivert 
Published: June 2021

Currently, an estimated 30.3 million Americans have diabetes, and experts predict 54.9 million Americans will have diabetes by 2030. The increasing prevalence of Type 2 diabetes (T2D) accounts for much of this expected growth. T2D is characterized by insulin resistance, which eventually leads to a reduction in functional β‐cell mass. Thus, treatments that increase β‐cell proliferation, survival, and function have the potential to reverse the effects of diabetes. One treatment that has shown promise is the use of dietary cocoa flavanols. These compounds have shown the ability to prevent the onset of diabetes in mice. Furthermore, a recent study conducted by our lab demonstrated that monomeric cocoa flavanols improved insulin secretion by increasing mitochondrial respiration. In addition to stimulating insulin secretion, we hypothesize that cocoa flavanols may also confer antidiabetic effects by promoting β‐cell proliferation and protecting β‐cells from lipotoxicity‐mediated cell death. To that end, we present data that shows the effect of epicatechin (monomeric flavanol), oligomeric, and polymeric cocoa flavanols on β‐cell proliferation and survival. Our results demonstrated that epicatechin enhances β‐cell proliferation. This finding is important because only monomeric flavanols have been found at significant levels in circulation. Notably, several gut bacteria‐derived cocoa metabolites have also been observed and identified. Consequently, we tested the effects of several cocoa metabolites on β‐cell proliferation and survival as well. We found that the cocoa metabolite hippuric acid, also enhances β‐cell proliferation. Additionally, we suggest a mechanism for the observed increase in proliferation caused by epicatechin and hippuric acid. These findings strengthen the growing body of evidence that dietary cocoa flavanols can ameliorate the effects of T2D.Support or Funding InformationDiabetes Action Research and Education Foundation grant #475 to JSTThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Testing for epigenetic effects caused by high and low sugar diets in Drosophila melanogaster
Authors: Rujchanarong Denys , Carter Ashley 
Published: June 2021

Obesity is a major health problem and has been linked to a variety of factors including prenatal and juvenile nutritional environment. Nutritional environmental effects have been shown to have epigenetic effects in humans, mice, and Drosophila melanogaster. However, the degree to which a high‐sucrose diet influences obesity and has an epigenetic impact on offspring has not been as thoroughly investigated in males as in females. We therefore examined the effects of control, low‐sucrose, and high‐sucrose diets on both maternal and paternal obesity and epigenetic effects in the male and female members of the F1 and F2 generations. This study demonstrates that variation in sucrose induced changes in parental and offspring fecundity and size.Support or Funding InformationThis research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers; 8UL1GM118979‐02; 8TL4GM118980‐02; 8RL5GM118978‐02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Improving the Efficiency of Mitochondrial Capacity Measurements Using Near Infrared Spectroscopy
Authors: Beard Samuel J , Benefield Madison , Das Indrajit R , McCully Kevin K 
Published: June 2021

Near Infrared Spectroscopy (NIRS) has been used to noninvasively measure muscle mitochondrial capacity. Previous protocols have required 2 tests and up to 50 cuff inflations.PURPOSEDevelop a new protocol for testing mitochondrial capacity that decreases the number of ischemic cuffs, increases comfort for participants, and improves curve fitting of the data, all while retaining reliability of the test.METHODSThe forearm flexor muscles of sixteen young, healthy individuals were tested (23 ± 4.1 years). A resting metabolism value was collected after 5 min of complete rest before and after the test. The test involved 4 sets of 6 ischemic cuff inflations, preceded by 30s of electrically induced twitch contractions. Analysis was performed on mitochondrial metabolic rates using a customized MATLAB program.RESULTSThe post‐test resting metabolism values were higher than the pre‐test resting values (−0.038 ± 0.02, −0.018 ± 0.01, optical density units P<0.01). There was no significant difference in the mitochondrial capacity for the four sets (1.50 ± 0.51, 1.42 ± 0.54, 1.26 ± 0.41, 1.29 ± 0.47, P=0.76).CONCLUSIONThe main finding of this study is that a test of mitochondrial capacity using four sets of 6 cuffs can be performed in less time (t ≈ 25 min) than two sets of 22 cuffs (t ≈ 45 min). While the use of a post‐test resting metabolism value did slightly lengthen the time needed to complete the study in relation to using the pre‐test value, this value appeared to be more accurate than using the pre‐test resting metabolism. The use of the post‐test resting values provided lower residuals and better agreement with previous data on the forearm muscles. Improved data collection can enhance the usefulness of NIRS based measurements of mitochondrial capacity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Contribution of Changes in Body Composition and Adaptive Thermogenesis to the Decline in Resting Metabolic Rate During Prolonged Calorie‐Restricted Weight Loss
Authors: Fox Darius M , Martin Alexandra R , Murphy Chaise A , Koehler Karsten 
Published: June 2021

In the United States, 2 out of 3 adults are overweight or obese. To lose weight, individuals engage in a variety of dietary and exercise interventions. Despite successful weight loss initially, weight loss is typically less than expected and most individuals regain weight. Both phenomena have been linked to a reduction in resting metabolic rate (RMR) secondary to weight loss.ObjectiveTo characterize the independent contributions of changes in body composition, the major predictor of RMR, and adaptive thermogenesis to the observed decline in RMR associated with weight loss. We predict that changes in fat‐free mass and adaptive thermogenesis will both contribute to RMR decline.MethodsSecondary data analysis was conducted on a publically available data set from CALERIE (Comprehensive Assessment of Long‐term Effects of Reducing Intake of Energy), a 2‐year observational calorie restriction study. CALERIE data used for the present analysis examined changes in RMR, body composition, and metabolic hormones over 12 months of 25% calorie restriction in 117 non‐obese (BMI between 22–27.9 kg/m2) men and women with complete data. Changes in RMR were compared between quartiles based on loss of body weight, fat‐free mass, and fat mass. Adaptive thermogenesis was quantified as the reduction in RMR that exceeded the reduction in RMR predicted from changes in organ mass, which was assessed by Dual‐energy X‐ray absorptiometry.ResultsAfter 12 months, mean weight loss was 7.9 ± 0.3 kg (−10.9 ± 0.4%, p<0.001 vs. baseline), and RMR declined by 101 ± 11 kcal/d (−6.8 ± 0.8%, p<0.001 vs. baseline). Individuals who lost the most weight (Q1ΔBW) demonstrated a greater RMR decline than individuals who lost the least weight (Q4ΔBW, p<0.01). The change in RMR did not differ between quartiles based on fat free mass loss (p=0.15), but it was positively associated with the amount of fat loss (p=0.03). In addition, participants who lost the greatest amount of fat mass (Q1ΔFM) exhibited a more pronounced adaptive thermogenic effect (−79 ± 19 kcal/d) than participants with the least amount of fat loss (Q4ΔFM; −10 ± 26 kcal/d, p<0.05 vs. Q1ΔFM). Adaptive thermogenesis was correlated with declines in leptin (r=0.27, p<0.01), T3 (r=0.19, p < 0.05), and insulin (r=0.25, p<0.05).ConclusionsDuring weight loss, the loss of fat mass and adaptive thermogenesis appear to be stronger predictors of RMR decline when compared to the loss of fat‐free mass.Support or Funding InformationThis work was funded in part by the University of Nebraska‐Lincoln McNair Scholars Program and the Undergraduate Creative Activities and Research Experience.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alpha Arrestin Domain Containing 2 and Alpha Arrestin Domain Containing 3 Expression is Reduced in Skeletal Muscle by Anabolic Stimuli and Increased by Catabolic Stimuli
Authors: Gordon Bradley Scott , Rossetti Michael L , Kimball Scot R 
Published: June 2021

Skeletal muscle is a highly plastic organ capable of increasing or decreasing in size depending upon the stimuli placed upon it. While this is known, the molecular factors that contribute to changes in skeletal muscle mass under anabolic and catabolic conditions remain ill defined. As such, the objective here was to identify novel genes that likely contribute to changes in skeletal muscle mass following anabolic or catabolic stimuli. For the initial identification of such genes, male mice were fasted overnight to induce a catabolic state in the skeletal muscle. The next morning, half of the mice were allowed to refeed for 30 minutes to effectively impart an anabolic stimulus on the skeletal muscle. Using an unbiased microarray approach and subsequent qRT‐PCR validation, the refeeding stimulus resulted in a significant reduction in the mRNA expression of Alpha Arrestin Domain Containing 2 (Arrdc2) and Alpha Arresting Domain Containing 3 (Arrdc3) in the tibialis anterior (TA) muscle. The reduction in Arrdc2 and Arrdc3 mRNA expression was not limited to nutrient consumption or the TA muscle as mechanical overload also reduced Arrdc2 and Arrdc3 expression in the TA and plantaris muscles. Moreover, the combination of nutrient consumption with mechanical overload had a synergistic effect on reducing Arrdc2 and Arrdc3 expression. Interestingly, these reductions in Arrdc2 and Arrdc3 expression following mechanical overload occurred even when signaling through the mechanistic target of rapamycin in complex 1 (mTORC1) growth pathway was disrupted. On the converse, Arrdc2 and Arrdc3 mRNA expression was increased in the muscle by catabolic stimuli other than fasting, which included androgen deprivation and the metabolic stress imposed by an acute bout of aerobic exercise. The divergent changes in Arrdc2 and Arrdc3 mRNA expression in the skeletal muscle following anabolic and catabolic stimuli were consistently related to the corresponding changes in markers of autophagy activation. While Arrdc2 and Arrdc3 expression showed consistent and divergent changes in expression under these conditions, no consistent changes in expression of other members of the Alpha Arresting Domain Containing family of genes were observed. In all, these data suggest changes in Arrdc2 and Arrdc3 expression may contribute to the regulation of skeletal muscle mass following anabolic and catabolic stimuli by altering autophagy activation.Support or Funding InformationNIH‐DK15658 (SRK) and FSU Council on Research and Creativity (BSG)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.