bluuebunny/crossref_metadata_2025_split huggingface dataset:
The functional role of brown adipose tissue in whole‐body lipid metabolism in humans (1160.3)
Authors: Chondronikola Maria , Porter Craig , Hurren Nicholas , Chao Tony , Yfanti Christina , Labbé Sebastien , Annamalai Palam , Volpi Elena , Børsheim Elisabet , Sidossis Labros 
Published: June 2021

Despite intense scientific interest regarding the role of human brown adipose tissue (BAT) in substrate metabolism, its role in whole‐body lipid metabolism remains unclear. To address this issue, we studied otherwise matched men with high (HBAT, n=7) and low (LBAT: n=5) BAT volume (69±18 mL vs. 4±2 mL, p<0.05) under cold exposure (CE) and thermoneutral (TN) conditions using positron emission tomography‐computed tomography, stable isotope infusions, and indirect calorimetry. For HBAT, but not LBAT participants, plasma free fatty acid concentrations (TN: 0.36±0.01mmol/L vs. CE: 0.63±0.01mmol/L, p<0.05), plasma glycerol concentrations (TN: 0.05±0.01 mmol/L vs. CE: 0.09±0.01 mmol/L, p<0.05), lipolysis (TN: 2.2±0.3 μmol/kg/min vs. CE: 5.9±0.6μmol/kg/min, p<0.05), and plasma free fatty acid oxidation (TN: 2.7±0.6 μmol/kg/min vs. CE: 5.9±1.0 μmol/kg/min, p<0.05) were higher under CE conditions than TN conditions. Moreover, during CE, plasma small LDL and large HDL particles increased more in the HBAT group than in the LBAT group (p<0.05). Finally, the HBAT group tended to have decreased plasma triglyceride concentrations the day after CE (‐33.4±11.4 mg/dl, p=0.06), whereas LBAT subjects showed no significant change. These novel findings demonstrate a functional role of BAT in human lipid metabolism.Grant Funding Source: : CTSA UL1TR000071, Pepper Center Pilot Grant, Sealy Center on Aging, Shriners Hospitals
The developmental transition of epicardial, paracardial and omental adipose tissue during early life in the sheep (1160.7)
Authors: Davies Graeme , Birtwistle Mark , Pope Mark , Perry Vivienne , Sacks Harold , Budge Helen , Symonds Michael 
Published: June 2021

Study objective: This study focused on the transition of epicardial, paracardial and omental fat during early postnatal life using analysis of gene expression.Methods: Sheep were euthanased for adipose tissue sampling at 1, 7 and 28 days of age (n=4 per time point) under UK Home Office Approval. Paracardial adipose tissue was sampled at all ages, whereas epicardial and omental adipose tissues were only present at 7 and 28 days. RNA was extracted and gene expression analysed by qRT‐PCR. Data was analysed using one‐way ANOVA or unpaired t‐Test.Results: With increasing age, the white fat markers leptin and RIP140 mRNA expression increased in all depots studied. PPAR gamma, involved in adipocyte differentiation, also increased with age. Conversely, uncoupling protein (UCP)1 mRNA abundance decreased with age. Putative mRNA markers of brown (lhx8) and beige (tmem26) adipose tissue in rodents were below the limits of detection in all fat depots studied.Conclusions: This study suggests a brown to white fat transformation with increased adipocyte differentiation in all depots studied, irrespective of a fetal (e.g. paracardial) or postnatal (e.g. omental) origin.
Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, obese individuals (1161.7)
Authors: Kim Il‐Young , Bodenner Donald , Wolfe Robert , Coker Robert 
Published: June 2021

Context: Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been evaluated in older individuals.Objective: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low‐dose lysine (2 g), and oral glucose and high dose lysine (5 g) lysine in 7 older (66±1 years/age), overweight (BMI = 31±2 kg/m2) individuals.Methods: We utilized a dual tracer technique (ie., [1‐13C] glucose oral ingestion and [6,6‐2H2] glucose infusion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios.Results: Plasma glucose and insulin data were not different between the control, 2 g lysine and 5 g of lysine trials. The results of the Matsuda index were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2±0.1, 1.1±0.1, 1.3±0.1 mg•kg‐1•min‐1), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2±0.2, 4.3±0.2, and 4.5±0.4 mg•kg‐1•min‐1), respectively.Conclusions: Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. Unfortunately, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.Grant Funding Source: NIH grants 1P30AG028718‐01A2; UL1TR000039 and KL2TR000063
Exercise training prevents myocardial infarction induced‐skeletal muscle atrophy by reducing oxidative stress in rats (1163.6)
Authors: Cunha Telma , Bechara Luiz , Bacurau Aline , Fernandes Tiago , Scavoni Cristoforo , Gabriel Daniele , Ferreira Julio , Brum Patricia 
Published: June 2021

Heart failure (HF) is a syndrome that compromises not only cardiovascular system, but other tissues, such as skeletal muscle. Skeletal muscle atrophy (SMA) is an independent predictor of mortality and oxidative stress is one of factors related to this atrophy. The objective of this study was to evaluate the role of oxidative stress in SMA induced by HF and the effect of aerobic exercise training (AET) in modulating this mechanism. Male rats were randomly assigned into groups: myocardial infarction (MI) and fictitious surgery (SHAM). These groups were submitted or not to 8 weeks of AET (1h running sessions at 60%VO2max) and were named sedentary or trained (MI‐SED; MI‐T; SHAM‐SED; SHAM‐T). All the values were presented as mean ± SE. To compare results, two‐way ANOVA was applied with Duncan pos hoc when necessary (p<0.05). The MI‐SED rats presented reduced plantaris cross‐sectional and AET prevented this atrophy and improved exercise tolerance in MI‐T. MI induced oxidative stress and AET attenuated oxidative stress biomarkers. Serum TNF‐α was elevated in MI‐SED and AET restored the MI values to SHAM‐SED levels (SHAM‐SED: 3.8 ± 0.5 vs. MI‐SED: 6.2 ± 28 vs. MI‐T: 3.2 ± 0.4 pg/µg). NF‐kB activity, which is a proteolysis marker, was reduced in MI‐T when compared to MI‐SED (MI‐T: 16228.3 ± 1621.5 vs. MI‐SED 20870.7 ± 927.8 A.U.). p38 MAPK levels were elevated after MI with no impact of AET on that levels (SHAM‐SED: 1.0 ± 0.21 vs. MI‐SED: 2.74 ± 0.26 vs. MI‐T: 1.6± 0.24 A.U.). Taking together these data provide evidence for oxidative stress associated with HF‐induced SMA and AET prevented atrophy by reducing oxidative stress and NF‐kB signaling pathway in MI rats.Grant Funding Source: FAPESP
Study of a multiprotein complex involved in excitation‐transcription coupling in skeletal cells (1164.9)
Authors: Arias‐Calderón Manuel , Almarza Gonzalo , Contreras‐Ferrat Ariel , Jaimovich Enrique , Buvinic Sonja 
Published: June 2021

Pannexin‐1 (Panx1) releases ATP to the extracellular space in skeletal muscle cells in response to electrical stimulation. ATP is a relevant mediator between membrane depolarization and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin1 channels (PnX1, ATP release conduit), nucleotide receptors, and several signaling molecules. The goal of this study was to assess protein‐protein interactions within the E‐T machinery in several models. Newborn derived myotubes, adult fibers, triad fractions from rat or mouse skeletal muscles and L6 cells overexpressing PnX1 have been used. In all the models co‐immunoprecipitation between DHPR, PnX1, P2Y2 receptor and dystrophin has been detected. Using 2D blue‐native SDS/PAGE we detected that DHPR, PnX1, P2Y2, caveolin3 and dystrophin belong to the same multiprotein complex. Using the proximity ligation assay associated to confocal microscopy, we observed co‐localization between DHPR, PnX1, P2Y2 and caveolin3.Unveiling the molecular actors involved in the regulation of gene expression could contribute to the understanding and treatment of skeletal muscle disorders such as muscular dystrophies and sarcopenia associated with aging.Grant Funding Source: Supported by Fondecyt‐1110467‐11100454, Conicyt‐79090021, FONDAP‐15010006, ACT‐1111
Progressive vasoconstrictory sympathetic outflow via muscle metaboreflex activation gradually increases human arterial stiffness (1165.4)
Authors: Prodel Eliza , Fernandes Igor , Barbosa Thales , Hawerroth Pedro , Nobrega Antonio Claudio , Vianna Lauro 
Published: June 2021

Previous studies demonstrated that stepped intravenous infusion of noradrenaline increases aortic and peripheral arterial stiffness. However it is unknown whether these findings could be extended to physiological stimulation. Given this, we tested the hypothesis that a graded vasoconstrictory sympathetic outflow via skeletal muscle metaboreflex activation would gradually increase human aortic arterial stiffness (AIx). In nine healthy male subjects (22±2 yr), the graded isolation of the muscle metaboreflex was achieved by post‐exercise ischemia (PEI) following moderate and high intensity static handgrip performed at 30% and 40% maximum voluntary contraction, in a counterbalanced order. Heart rate (ECG), mean arterial pressure (MAP), Alx (SphygmoCor) and radial artery diameter (Doppler) were measured. MAP increased significantly from rest during PEI30% (105±4 mmHg vs 83±2 mmHg; P<0.05) and was a further augmented during PEI40% (115±3 mmHg vs PEI30%; P<0.05), indicating graded metaboreflex activation. Similarly, Alx increased significantly from rest during PEI30% (Rest ‐9±3% vs PEI30% 9±5%, P<0.05) and was further augmented during PEI40% (17±4% vs PEI30%; P<0.05). Radial artery diameter was unchanged throughout. The present results extend previous findings from pharmacological studies by showing that progressive muscle metaboreflex activation gradually increases human arterial stiffness.Grant Funding Source: Supported by CAPES, CNPq, FAPERJ, FINEP
Purinergic 2X receptors play a role in evoking the exercise pressor reflex in rats with peripheral artery insufficiency (1165.6)
Authors: Stone Audrey , Yamauchi Katsuya , Kaufman Marc 
Published: June 2021

Purinergic 2X (P2X) receptors on the endings of thin fiber afferents have been shown to play a role in evoking the exercise pressor reflex in cats. In this study, we attempted to extend this finding to decerebrated, unanesthetized rats whose femoral arteries were either freely perfused or were ligated 72 hours before the start of the experiment. We first established that our dose of PPADS (10 mg/ kg), a P2X receptor antagonist, attenuated the pressor response to α, β methylene ATP (10 µg/ kg), a P2X receptor agonist. We then compared the exercise pressor reflex before and after infusing PPADS into the arterial supply of the hind limb muscles that were statically contracted. In rats with freely perfused femoral arteries, the peak pressor responses to contraction were not significantly attenuated by PPADS (before PPADS: 19±2mmHg, 13 min after PPADS: 17±2mmHg, and 25 min after PPADS: 17±3mmHg). Likewise, the cardioaccelerator and renal sympathetic nerve responses were not significantly attenuated. In contrast, we found that in rats whose femoral arteries were ligated, PPADS significantly attenuated the peak pressor responses to contraction (before PPADS: 37±5mmHg, 13 min after PPADS: 27±6mmHg, 25 min after PPADS: 25±5mmHg; p<0.05). Heart rate was not significantly attenuated, but renal SNA was at certain time points over the 30s contraction period. We conclude that P2X receptors play a role in evoking the exercise pressor reflex in rats whose femoral arteries were ligated, but do not play a role in evoking the reflex in rats whose femoral arteries were freely perfused.Grant Funding Source: Supported by NIH grants HL‐096570 and AR‐059397
Hyperaminoacidemia eliminates the influence of body fat and insulin sensitivity on fractional synthesis rate and myostatin regulation in humans (1168.3)
Authors: Tran Lee , Masters Haley , Katsanos Christos 
Published: June 2021

Multiple conditions are linked to perturbed skeletal muscle protein (SMP) metabolism, including excess adiposity and insulin resistance. Here we delineate the precise roles of body fat and insulin sensitivity on SMP metabolism, and test the hypothesis that hyperaminoacidemia can eliminate the influence of these factors. Six healthy individuals underwent a DEXA scan to determine percent body fat (%BF; 16.3‐29.4%) and an oral glucose tolerance test (OGTT) to evaluate insulin sensitivity via Matsuda index (MI; 1.21‐12.0). Subjects received a primed, continuous infusion of L‐[2,3,3,4,5,5,5,6,6,6‐2H10]leucine to determine SMP fractional synthesis rate (FSR) in biopsies from the vastus lateralis. Myostatin (MSTN) mRNA, a marker of muscle wasting, was quantified in similar biopsies, and MSTN activation was assessed in plasma as the percent of active over latent protein. To evaluate the effect of hyperaminoacidemia, samples were collected before and during infusions of high amino acids (AA). In our subjects, %BF was not correlated with MI (P=0.11). The %BF was only associated with MSTN mRNA (P=0.02; r=0.81). However, MI was a key determinant in FSR (P=0.02; r=0.83) and MSTN activation (P<0.01; r=‐0.94). AA infusion eliminated all discrepancies in FSR and MSTN quantitations. Thus, SMP metabolism is more strongly linked to insulin sensitivity than body fat, but the influence is attenuated with hyperaminoacidemia.Grant Funding Source: Supported by NIH/NIDDK Grant# R01 DK094062; NCATS Grant# UL1 TR000135
Angiotensin II‐induced inhibition of sodium currents in aortic baroreceptor neurons mediates blunted arterial baroreflex sensitivity in heart failure rats (1169.3)
Authors: Liu Jinxu , Zhang Dongze , Zheng Hong , Muelleman Robert , Li Yu‐Long 
Published: June 2021

Impairment of arterial baroreflex sensitivity (ABS) is associated with increased mortality in patients with chronic heart failure (CHF). Increase in plasma angiotensin II (Ang II) level is often seen in CHF and contributes to the baroreflex dysfunction. Our previous studies have confirmed that reduced expression of voltage‐gated sodium (Nav) channels in aortic baroreceptor (AB) neurons is involved in attenuation of the ABS in CHF rats. In this study, we investigated acute effect of Ang II on Nav currents in AB neurons and on the ABS from sham and CHF rats. Using Ang II 125I radioimmunoassay, real‐time PCR and western blot, we found that Ang II level, mRNA and protein expression of Ang II type 1 (AT1) receptor in nodose ganglia (NG) from CHF rats were higher than that from sham rats. Data from whole cell patch‐clamp recording showed that Ang II (100 nM) acutely inhibited Nav currents in A‐ and C‐type AB neurons from sham and CHF rats. AT1 receptor antagonist losartan (1 µM) totally abolished the effect of Ang II on Nav currents. In addition, the inhibitory effect of Ang II on Nav currents was larger in CHF rats than that in sham rats. Local microinjection of Ang II (0.2 nmol) into the NG decreased the ABS in sham rats. However, local losartan (1 nmol) improved the blunted ABS in CHF rats. These results suggest that elevated endogenous Ang II in the NG contributes to the impaired ABS in CHF rats through inhibiting Nav channels.Grant Funding Source: Supported by National Heart, Lung, and Blood Institute grant HL‐098503 (to Y.‐L.L.)
Baroreflex sensitivity during intestinal ischemia (1169.6)
Authors: Aletti Federico , Gambarotta Nicolò , Penn Alexander , Baselli Giuseppe , Schmid‐Schönbein Geert , Ferrario Manuela 
Published: June 2021

Autonomic control of heart rate (HR) during prolonged intestinal ischemia was investigated by mathematical analysis of cardiac baroreflex. 24 Wistar rats underwent splanchnic arterial occlusion (SAO) under anesthesia and received different treatments, which included enteral saline or glucose, intramuscular xylazine and i.v. glycopyrrolate. High fidelity continuous arterial blood pressure (ABP) was measured by a catheter placed in the femoral artery. Time series of systolic blood pressure (SBP) and heart period (HP) were derived from the continuous ABP. Baroreflex gain (from SBP to HP) was calculated both in the low frequency (LF, 0.25‐0.75 Hz) and high frequency (HF, 0.75‐2.5 Hz) spectral bands. After a variable delay, ABP began to steadily decrease until either sacrifice at 4 hours after SAO or collapse by a sudden, fast fatal drop (FFD) of ABP. FFD was prevented by treatment with glycopyrrolate. Rats who displayed the FFD had a higher LF gain in the period (~ 5 mins) preceding the FFD with respect to the post‐SAO period (0.22 ± 0.11 ms/mmHg vs. 0.36 ± 0.15 ms/mmHg, p‐value < 0.05). These preliminary results suggest a sympathetic hyperactivation in the FFD rats and hint that the sympathetic system reaches saturation before the FFD, with the possibility of a sudden shift of the sympatho‐vagal balance towards a parasympathetic driven control of HR.Grant Funding Source: Supported by the ShockOmics project of the European Union (Grant#602706)
Statin therapy decreases cardiac sympathetic activity in patients with left ventricular dysfunction: a 123l‐MIBG myocardial scintigraphy study (1169.9)
Authors: Fernandes Igor , Vianna Lauro , Freitas Raphael , Miranda Sandra , Mesquita Evandro , da Nóbrega Antonio , Mesquita Claudio 
Published: June 2021

Convincing animal and human studies indicate that statin therapy decreases renal and muscle sympathetic nerve activity. Reduced cardiac sympathetic drive and innervation have also been reported as pleiotropic consequences of statin therapy in a rat coronary ligation model. This study then investigated whether these results could be translated to a clinical setting of human left ventricular dysfunction. Washout rate (WR) and heart‐to‐mediastinum (H/M) ratio, indexes of cardiac sympathetic activity and innervation density, were obtained from planar 123l‐metaiodobenzylguanidine myocardial scintigraphy images of patients undergoing long‐term statin [30±7 mg/day for at least a month] (7 men and 4 women, NYHA class II‐III, ejection fraction of 45±5%, age of 53±4, and body mass of 83±5 kg) and only standard drug therapy (7 men and 6 women, NYHA class II‐III, ejection fraction of 37±7%, age of 57±2 years, and body mass of 77±7 kg). Resting cardiovascular variables and lipid profiles were similar between groups. Statin users presented lower WR (Statin 29±2% vs. SDT 39±1, P<0.05) whereas early (1.7±0.2 vs. 1.6±0.2, P>0.05) and late (Statin 1.6±0.2 vs. SDT 1.6±0.4, P>0.05) H/M were similar for both groups. Our findings partially extend the results of animal studies and indicate that statin therapy reduces cardiac sympathetic activity in patients with left ventricular dysfunction without changing innervation density.Grant Funding Source: Supported by CAPES, CNPq, FAPERJ, FINEP.
Health benefits of wholegrain ő a systematic review of the evidence to propose a daily intake recommendation (117.1)
Authors: Chanson‐Rollé Aurélie , Lappi Jenni , Meynier Alexandra , Poutanen Kaisa , Vinoy Sophie , Braesco Véronique 
Published: June 2021

Objectives: Recommendations on wholegrain (WG) consumption are widespread but rarely quantitative. This work attempted to systematically review published human studies to quantify the daily intake of WG associated to favourable health outcomes. Results related to cardiovascular diseases (CVD) and type‐2 diabetes (T2D) are presented here.Methods: Databases were searched from 1993 to 2012. Retrieved papers were screened by 3 PhDs. Six articles were selected for each outcome. A meta‐analysis was done using multivariate‐adjusted risk ratios of CVD comparing highest and lowest WG intake levels. Then, meta‐regressions were performed on CVD and T2D rates relative to WG amounts by using a hierarchical mixed linear model.Results: First, we confirmed a significant inverse association between WG intake and CVD risk (overall RR = 0.84; p=0.004). Although quantitative meta‐regression failed to demonstrate a significant relationship between WG intake and CVD rate, a significant relationship was observed for T2D (p<0.0001), with an overall reduction of 0.03% in T2D incidence for each additional g of WG consumed daily.Conclusion: A significant association was observed between WG intake and T2D occurrence. Consuming 45 g/d of WG ingredients would decrease T2D risk by 21% as compared to consuming 7.5 g/d. This amount of WG, in line with current recommendations in North America, should be considered for recommendations.
Effects of dairy vs. sugar‐sweetened products on insulin sensitivity, pancreatic β‐cell function and plasma lipids in men and women at risk for type 2 diabetes mellitus (117.3)
Authors: Maki Kevin , Nieman Kristin , Schild Arianne , Kaden Valerie , Lawless Andrea , Kelley Kathleen , Rains Tia 
Published: June 2021

This randomized, controlled, crossover trial assessed the effects of dairy (2 servings/d 2% milk and 1 serving/d low‐fat yogurt) vs. sugar‐sweetened (2 servings/d non‐diet soda and 1 serving/d non‐dairy pudding) product consumption for 3 wk on insulin sensitivity, β‐cell function, and plasma lipids. Subjects were 34 consumers of sugar‐sweetened beverages (蠅2 servings/d), 50% female, mean age 53.8 y and BMI 32.2 kg/m2, with multiple risk factors for type 2 diabetes mellitus (T2DM). A liquid meal tolerance test (LMTT) was administered at baseline (BL) and the end of each treatment. Changes from BL (dairy condition shown first) were significantly different between conditions for mean homeostasis model assessment insulin sensitivity (HOMA‐%S; 17.8 vs. ‐17.3%; P = 0.01; BL = 127.1%), LMTT disposition index (‐0.03 vs. ‐0.36; P = 0.01; BL = 2.59), and HDL‐C (0.8 vs. ‐4.2%; P = 0.01; BL = 44.3 mg/dL). Median changes from BL in LMTT Matsuda insulin sensitivity index (0.54 vs. ‐0.26; BL = 4.16) and HOMA β‐cell function (0.5 vs. 3.8%; BL = 68.4%) did not differ significantly between treatments. These results suggest that dairy consumption, compared with sugar‐sweetened products, improves HOMA‐%S, LMTT disposition index, and HDL‐C in men and women at‐risk for T2DM.Grant Funding Source: Dairy Research Institute