bluuebunny/crossref_metadata_2025_split huggingface dataset:
A monoclonal antibody targetting the FGFR‐1c isoform reduces body weight and food intake, which is, associated with a suppression of deiodinase 2 mRNA expression in hypothalamic tanycytes
Authors: Samms Ricardo , Lory Alex , Roberts Jessica , Warner Amy , Sundquis Sarah , Emmerson Paul , Perry Barrett , Tsintzas Kostas , Ebling Fran 
Published: June 2021

FGF21 plays a role in the peripheral regulation of energy balance, but its putative receptor (FGFR1c) is also expressed in tanycyte cells of the hypothalamus. The objective of the present study was to investigate the possible central actions of a monoclonal antibody (H7) that specifically targets FGFR1c in a natural model of adiposity, the Siberian hamster. Hypothalamic thyroid hormone availability, controlled by tanycytes, is the key regulator of seasonal cycles of body weight, so we aimed to determine the effect of H7 on local regulators of thyroid hormone availability: deiodinase enzymes DIO2 and DIO3. Hamsters maintained in their long day fat state (LD; n=12) or short day lean state (SD; n=12) were treated with H7 (n=6, 3 mg/kg, sc) or vehicle (n=6/photoperiod). This resulted in a significant reduction in food intake over the 72h treatment period in hamsters in LD (~60%), and a smaller reduction in food intake in SD (~40%). In LD, treatment with H7 resulted in a significant decrease (~50%) in DIO2 mRNA expression in the tanycyte layer of the medial basal hypothalamus. In SD, endogenous DIO2 expression was significantly lower than in LD as expected but H7 treatment did not significantly decrease its expression. In summary, a monoclonal antibody specifically targeting the FGFR1c isoform reduces food intake and body weight in a natural model of adiposity. These effects are far more substantial in hamster maintained in their LD fat state and appear to be associated with the reduction in mRNA expression of the deiodinase enzyme, DIO2.Supported by Eli Lilly and a BBSRC studentship.
Sensitivity of forearm critical power to acute manipulation of perfusion pressure
Authors: Kellawan Mikhail , Bentley Robert F , Walsh Jeremy J , Moynes Jaclyn S , Tschakovsky Michael E 
Published: June 2021

PURPOSEWe tested the hypothesis that manipulating perfusion pressure (PP) impacts forearm critical power (fCP).METHODS9 healthy young (23 ± 2.6 yrs) males completed 10 min fCP tests in each of arm above (A) and below (B) heart level (forearm PP A < B by ~30 mmHg). fCP (average of force impulse in last 30 s of test), forearm blood flow (FBF; echo and Doppler ultrasound), arterial pressure (MAP; finger photoplethysmography), O2 consumption (VO2; venous blood samples, Fick eqn) were measured during exercise.RESULTSmean ± SD. Responders (all with compromised fCP in A vs. B; 21 ± 7 vs. 30 ± 6 kg·s, p=0.01) and non‐responders (no compromise to fCP in A vs. B; 29 ± 17 vs. 27 ± 16 kg·s, P=0.14) were identified. Responders exhibited O2D compromise in A vs. B (164 ± 60 vs. 178 ± 65 ml O2/min, p=0.04), and all had lower VO2 in A vs. B but this was not statistically significant (VO2 88 ± 30 ml/min vs. 104 ± 40 ml/min, p=0.12). Non‐responders had no compromise to O2D in A vs. B (153 ± 26 vs. 164 ± 28 ml O2/min, p=0.53), nor any compromise to VO2 (99 ± 21 ml/min vs. 106 ± 28 ml/min, p=0.58). No clear pattern regarding pressor or vasodilatory compensation to protect O2D was found (Responders A vs. B, ΔFVC p=0.01, ΔMAP p=0.12; Non‐responders A vs. B ΔFVC p=0.22, ΔMAP p=0.37).CONCLUSIONSReductions in perfusion pressure can reduce forearm critical power in individuals who cannot defend O2D. These data highlight the importance of O2D to fCP. NSERC
Mechanical Tissue Resuscitation (MTR) reduces myocardial tissue injury following myocardial ischemia‐reperfusion (MI/R)
Authors: Jordan James E. , Mays Jennifer J. , Shelton Julie E. , Thompson Edreca A. , Bryant Allyson K. , Lane Magan R. , Morykwas Michael J. 
Published: June 2021

BackgroundReperfusion following an ischemic myocardial event increases cell death by activation of inflammatory processes. Reducing reperfusion injury may improve morbidity and mortality following AMI. We have previously shown MTR to reduce infarct size following MI/R. Here, we determine the effects of MTR on apoptosis and edema using a novel, bio‐absorbable patch.MethodsA left, anterior free‐wall ischemic lesion (80 minutes) was created using reversible tourniquets in swine. Animals were randomized to receive either no treatment (Control) or MTR (− 50mmHg) using a bio‐absorbable patch at reperfusion. Following 3 hours of reperfusion, infarct size, apoptosis and edema were determined.ResultsWhile both groups had similar areas at risk (AAR/LV, 13.2 ± 0.7% and 14.8 ± 0.5%; p=.09), infarct size (AN/AAR) was significantly reduced in MTR‐treated animals (16.8±2.8%, p <.05) compared to controls (26.4±2.8%). This myocardial protection was accompanied by a reduction in epicardial apoptosis (7.7 ± 1.9% vs. 29.3 ± 7.7% TUNEL positive cells). MTR also reduced interstitial space in the endocardium by 53% and in the epicardium by 34%.ConclusionsMTR applied directly over the infarcted area of the heart by means of a bio‐absorbable patch results in tissue preservation which may be the result of changes in apoptosis and edema formation. These data suggest that MTR could be an appropriate therapeutic approach to decrease myocyte death following a myocardial infarction.
Effect of Unilateral E‐Stim on Strength in a Contralateral Untrained Limb After Bilateral Strength Training
Authors: LoRusso Stephen , Barr Nathaniel , Hanik William , Hazen Joshua , Strittmatter Amanda , Tocco Tatum 
Published: June 2021

Unilateral strength training or electrical stimulation increases strength in an untrained, contralateral limb. This cross education effect is similar to conventional training. We have shown reduced strength loss in a contralateral untrained limb with unilateral strength training after 4 weeks of bilateral leg extension training.MethodsIn a pre‐and post‐test design, 18 subjects, aged 18–35, not engaged in structured strength training for 3 months, were randomly assigned to a unilateral strength training (U), e‐stim training (E), or control group(C). All subjects underwent 4 weeks of bilateral leg extension training, then for 4 weeks, either stopped training, or trained the right limb with strength training or e‐stim. A pre‐training, 4 week post‐training and final unilateral 1 RM for leg extension was obtained.ResultsAfter 4 weeks of bilateral training, unilateral 1 RM strength significantly increased (left leg p=0.001; right leg p=0.000). However, during the final 4 weeks, all subjects lost strength in the trained and untrained limbs. The percent change in the untrained and trained limbs respectively were: Group E −4.23%; −1.20%; Group U −6.05%; −0.78% and Group C −8.47%; −6.55%.ConclusionAt these training loads, neither unilateral strength training or e‐stim had a significant effect on the trained or untrained limb, and therefore were unable to prevent strength loss in either limb.
Low volume high intensity training improves insulin sensitivity but reduces aerobic power in trained middle‐aged runners
Authors: Winding Kamilla , Hansen Louise Seier , Knudsen Trine Alma , Hellsten Ylva , Mortensen Stefan Peter , Pedersen Bente Klarlund 
Published: June 2021

ObjectiveTo investigate if high intensity interval training (HIIT) improves performance and insulin sensitivity in trained middleaged runners.MethodsSixteen male runners (47±2 years and VO2max of 50±2 mlO2/kg/min) were randomly assigned to 6 weeks of HIIT (6–10 one minute intervals at 100% maximal running speed, 3 times per week) or habitual training (CON). HIIT replaced ~25–44% of the subjects’ aerobic based training, reducing running volume by 26.2% compared to before the experiment. Before and after the training period, performance was tested on the treadmill and insulin sensitivity was measured by oral glucose tolerance test using the Matsuda Index. Resting muscle biopsies were also obtained from the m. vastus lateralis.ResultsHIIT improved the lactate threshold (P<0.001) and the velocity associated with VO2max (P<0.01) whereas they were unchanged in CON. HIIT training increased CD31 content (P<0.05), whereas VO2max (P<0.001) and the content of oxidative enzymes was reduced (P<0.05). The monocarboxylate transporter 4 and the Na+/H+ exchanger 1 were unchanged. Insulin sensitivity increased by 23±11% in the HIIT group (P<0.05), and was higher than the CON group after training (P<0.05).ConclusionIn middle‐aged runners, HIIT improves insulin sensitivity, but impairs aerobic power and oxidative enzyme content.
Perinatal Sulfur Dioxide Exposure Alters Brainstem Parasympathetic Control of Heart Rate
Authors: Woerman Amanda L , Mendelowitz David 
Published: June 2021

Sulfur dioxide (SO2) is an air pollutant that induces adverse cardiorespiratory health effects, including MI and tachycardia, and impedes neonatal development. We developed an animal model enabling characterization of in vivo alterations in heart rate (HR) and cellular changes in brainstem neurons that control HR after perinatal SO2 exposure. Pregnant Sprague Dawley rats were exposed to 5 ppm SO2 for 1 h daily throughout gestation and 6 days postnatal (P6). ECGs were recorded from pups at P5 to examine changes in basal HR elicited by perinatal SO2 exposure. In vitro studies used whole‐cell patch‐clamp electrophysiology to examine changes in transmission to cardiac vagal neurons (CVNs) within the nucleus ambiguus upon SO2 exposure using a preparation retaining fictive inspiratory activity. SO2 exposure increased HR, indicative of a loss of parasympathetic drive. Neither spontaneous nor inspiratory‐related GABAergic or glycinergic transmission to CVNs was altered by SO2 exposure, however glutamatergic transmission was decreased by 50%. This diminished excitatory transmission was TTX‐sensitive, indicating SO2 exposure impairs the activity of preceding glutamatergic neurons that synapse upon CVNs. Diminished glutamatergic, but unaltered inhibitory transmission to CVNs provides a mechanism for the observed SO2‐induced tachycardia via a loss of brainstem parasympathetic activity to the heart.Funded by NIH grants HL49965, HL59895, & HL72006 to DM, & GW Institute for Sustainability Research, Education, & Policy Research Award to ALW.
Short‐term sustained hypoxia affects synaptic transmission in the nucleus tractus solitarius neurons of juvenile rats
Authors: Accorsi‐Mendonça Daniela , Almado Carlos E.L. , Machado Benedito H. 
Published: June 2021

In the present study we evaluated the effects of a short‐term sustained hypoxia [(SH) 24 hours ‐ 10% O2] on intrinsic properties and synaptic transmission of nucleus tractus solitary (NTS) neurons of juvenile Wistar rats (P21). After 24 hours inside hypoxic or normoxic chambers rats were anesthetized, the brains removed and brainstems sliced. Intrinsic properties and excitatory currents of NTS neurons were recorded using whole‐cell patch clamp. SH did not change the resting membrane potential (control: −78.7 ± 2.4 mV n=15; SH: −72.3 ± 3.7 mV n=15), input resistance (control: 1.4 ± 0.4 G Ohm n=8; SH: 1.4 ± 0.4 G Ohm n=9) or capacitance of neurons (control: 14.2 ± 0.9 pF n=17; SH: 12.4 ± 0.8 pF n=15), indicating that SH does not change the intrinsic properties of NTS neurons. However, it was observed an increase in frequency of spontaneous currents (control: 3.6 ± 0.4 Hz n=18; SH: 7.1 ± 1.5 Hz n=15) and in peak amplitude of evoked currents (control: −289 ± 51 pA n=15; SH: −472 ± 64 pA n=15). Moreover, after a train of 5 stimuli, NTS neurons from SH group presented higher depression in glutamatergic events (relative amplitude of evoked currents; control: 100, 44, 34, 32 and 28%; SH: 100, 40, 28, 22 and 17%, *p<0.001, n=15), suggesting that SH affects the vesicular release probability. The data show that short‐term SH increases the spontaneous and evoked neurotransmitter release in the NTS neurons, which may explain, at least in part, the autonomic and respiratory changes observed in this experimental model.Financial support: FAPESP and CNPq.
Intermittent Hypoxia Induces Leptin Signalling in the Carotid Body
Authors: Ciriello John , Messenger Scott A. 
Published: June 2021

Glomus cells in the carotid body are responsible for detecting changes in blood PO2. These glomus cells have recently been found to express leptin receptors and are activated by intermittent hypoxia (IH) and systemic leptin injections, although the function of leptin within the carotid body remains unknown. The present study was done to investigate whether IH activates leptin signalling pathways within leptin‐expressing carotid body glomus cells. Rats were subjected to IH (120s normoxia, 80s hypoxia for 8 h) or normoxia (8h). Exposure to IH increased plasma leptin levels almost 6‐fold compared to normoxic controls. Additionally, IH was found to increase leptin, ERK1/2 and Fra‐1/2 immunoreactivity within glomus cells. Systemic leptin injections evoked similar effects on leptin, ERK1/2 and Fra‐1/2 immunoreactivity within the glomus cells. Furthermore, using Western blot analysis, IH was found to increase protein expression of leptin, the short form of the leptin receptor (Ob‐R100 kDa), pSTAT3 and SOCS3. On the other hand, IH induced a decrease in Ob‐Rb protein expression. Taken together, these data suggest that the increased levels of leptin within the circulation and those within the glomus cells induced by IH may function within the carotid body to alter the sensitivity of chemoreceptors to hypoxic stimuli.Supported by Heart and Stroke Foundation of Ontario
Carotid Body Denervation Attenuates Oscillations in Respiratory Rate and Sympathetic Nerve Activity, and Decreases Apnea/Hypopnea Index in Congestive Heart Failure
Authors: Marcus Noah J , Del Rio Rodrigo , Schultz Harold D 
Published: June 2021

Cheyne‐Stokes respiration is associated with increased morbidity and mortality in patients with congestive heart failure(CHF) and commonly coincides with high chemosensitivity. We hypothesized that incidence of disordered breathing patterns would be increased in a rabbit model of pacing‐induced CHF, and that denervation of the carotid body chemoreceptors (CBD) would attenuate these changes. Plethysmography was used to measure resting breathing pattern and the ventilatory responses to hypoxia (Hx) and hypercapnia (Hc). Sympathetic nerve activity was measured directly from the renal nerves (RSNA) of conscious animals. Resting respiratory pattern was quantified by an apnea‐hypopnea index (AHI) and a respiratory oscillation index. RSNA and ventilatory responses to Hx were augmented in CHF, and nearly abolished by CBD. CBD also resulted in a 40% reduction in Hc response. CHF resulted in increased incidence of oscillations in respiratory rate that were accompanied by surges in blood pressure, heart rate, and RSNA. The incidence of these oscillations was reduced after CBD (pre‐pace 26±3/h, CHF 48±5/h, CHF‐CBD 13±7/h). The AHI was increased with CHF and this increase was attenuated after CBD (pre‐pace 9±2, CHF 17±3, CHF‐CBD 5±1). Our findings suggest that CB denervation may be an effective treatment to reduce respiratory instability in CHF patients.Funding: NIH 1F32HL108592–01A1 & Coridea NC1.
Role of MMP‐2 activation in oncostatin‐M induced cardiomyocyte dedifferentiation
Authors: Fan Frank (Xiaohu) , Ali Mohammad A.M. , Hughes Bryan G. , Schulz Richard 
Published: June 2021

Despite the dogma that adult mammalian cardiomyocyte is terminally differentiated, these cells have a discrete regenerative capacity in both acutely and chronically injured human hearts. Dedifferentiation of cardiomyocytes is an important source of cardiac progenitor cells facilitating cardiac repair. Oncostatin‐M (OSM) can induce cardiomyocyte dedifferentiation characterized by sarcomere degeneration. However, the detailed mechanism regarding the downstream execution of sarcomere degeneration remains unclear. Matrix metalloproteinase‐2 (MMP‐2) is an important intracellular protease known to cleave multiple sarcomeric proteins including α‐actinin, troponin‐I and titin. We studied the dynamics of sarcomere degeneration upon stimulation of neonatal rat ventricular cardomyocytes (NRVM) with OSM. As early as 48 hr after OSM (50ng/ml) treatment, changes in sarcomeric structure were observed. Z‐bands stained for α‐actinin were degenerated towards Z‐bodies and M lines stained for titin also showed a similar pattern. The beating rate of NRVM significantly decreased, consistent with the observed sarcomere degeneration. Western blots and gelatin zymography analysis show increased MMP‐2 activity and loss of α‐actinin and troponin I following OSM treatment. These results suggest the possible involvement of MMP‐2 in cardiomyocyte dedifferentiation stimulated by OSM.Funding: Canadian Institutes of Health Research
Influence of regular endurance training on postexercise hemodynamic regulation to orthostatic challenge
Authors: Sugawara Jun , Komine Hidehiko , Miyazawa Taiki , Imai Tomoko , Ogoh Shigehiko 
Published: June 2021

Although postexercise syncope in endurance athletes is well recognized, the underlying mechanism is unknown. To determine whether endurance athletes exhibit the substantial hypotension during postexercise orthostatic stimulation, we conducted 5‐min head‐up tilt (HUT) tests before and after the 1‐hour moderate intensity cycling in young sedentary (S: n=8), endurance‐trained (E: n=8), and resistance‐trained (R: n=8) men. After the exercise the HUT‐induced vasoconstriction was significantly blunted in S and E groups. Significantly larger increase in the HUT‐induced fall of stroke volume was seen in E and R groups. Contrast to our hypothesis, endurance trained men did not exhibit a substantial drop of mean arterial pressure and/or pre‐syncope symptom during postexercise HUT despite the accumulated factors which facilitates orthostatic hypotension. This phenomenon might be explained by the greater augmentation of HUT‐induced tachycardia: the postexercise increase in tachycardia response was significantly greater in the endurance‐trained (+118% from preexercise) than those in the other groups (+45–50%). Collectively, during postexercise orthostatic challenge (at least in an early phase), endurance athletes maintain arterial pressure mainly by the enhanced tachycardia response.Grant: Nakatomi Foundation, Japan.
Low salt intake is associated with maternal obesity before and during pregnancy
Authors: Tresoldi Michelle Soto , Heimann Joel Claudio , Lopes Karen Lucasechi 
Published: June 2021

ObjectiveTo evaluate body weight, adipose tissue mass, serum leptin and mean blood pressure in females fed with different amounts of sodium chloride in three moments of the perinatal period: before (B) and at the end of pregnancy (P) and at the end of lactation (L).MethodsFemale Wistar rats were fed low (LS: 0.15%), normal (NS: 1.3%) or high (HS: 8%) salt diet since 8 weeks of age. Mating was induced at 12 weeks of age. The mass of white adipose tissue (WAT, g/100g), brown adipose tissue (BAT, g/100g), body weight (BW, g), serum leptin (SL, μg/mL) by radioimmunoassay, intra‐arterial mean blood pressure (BP, mmHg) and adiposity index (AI=WAT/BW × 100, %) were evaluated.Results (p<0.05, values represented by mean±SEM, n=4 to 10/group):In LS fed rats, BAT and SL were lower in L (BAT: 0.11±0.011; LS: 3.6±1.1) compared with B (BAT: 0.18±0.013; LS: 7.7±1.0) and P (BAT: 0.15±0.012; SL: 7.8±1.1). Also in LS fed rats, AI was lower in L (6.1±0.5) compared with B (8.1±0.6) and P (7.8±0.5). In L, BP was higher in HS (137.1±4.9) compared with NS (119.1±2.4) and LS (111.7±7.5). The BW was lower in HS (258.0±6.0) compared with NS (329.0±26.5) and LS (306.5±19.6) group.ConclusionsThe amount of dietary salt consumption during the perinatal period influences maternal energy metabolism and blood pressure.Supported by CAPES and FAPESP.
Improved satiety effect of leptin fusion proteins with prolonged plasma half‐life in mice
Authors: Bolze Florian , Morath Volker , Schneider Sarah , Mocek Sabine , Schlapschy Martin , Skerra Arne , Klingenspor Martin 
Published: June 2021

Leptin, a 16 kDa hormone derived from adipocytes, plays a key role in energy balance regulation. Its clinical application in disorders associated with low plasma leptin levels, like genetically caused leptin deficiency, has been proposed. Due to its low hydrodynamic volume leptin is rapidly eliminated by renal clearance. Thus, daily injections would be needed to perpetuate a constant effect, which is not acceptable as therapy.To improve leptin therapy, we have engineered leptin with an enlarged hydrodynamic volume using PASylation technology, which involves fusion with a disordered poly‐amino acid sequence comprising 200, 400 or 600 Pro, Ala and Ser residues (PAS). The expanded hydrodynamic volume reduces renal clearance in a length‐dependent manner. The affinity of the fusion proteins to the leptin receptor was almost fully retained as demonstrated by surface plasmon resonance analysis.Cell culture assays revealed that PAS‐variants were nearly as potent in activating receptor signaling as native leptin. In C57BL/6J mice, PAS‐derivates were able to reduce food intake and body weight in a more effective manner than native leptin. The strongest effect was observed for PAS600‐leptin with a 10 % weight loss over 5 days.Thus, PASylation is promising to maintain a lasting therapeutic effect without the need for daily injections.Supported by National Genome Research Network plus to M. Klingenspor (01GS0822)
Steatosis Response To Curcumin In An Obese Mouse Model
Authors: Nookala Asha , Quinn Tim , Herndon Betty , Molteni Agostino , Alba Laura , Nachnani Jagdish , Bulchandani Deepti 
Published: June 2021

Curcumin is a popular spice and part of the ancient medicinal system Ayurveda. It is known to have anti‐inflammatory, antimicrobial and antioxidant properties; research has shown prevention of liver damage induced by IL‐6. Here, we tested the hypothesis that the natural fatty livers in leptin k/o mice (OB/OB) would be improved by adding curcumin to food pellets, suggesting potential use in hepatic steatosis in general. Ten treated and ten control OB/OB mice were fed 2 months then studied for effects. Food pellets (Harlan) were prepared with and without 180 mg curcumin in the daily dietary intake (9 gm). Calories for both diets: protein 15.2%, carbs 62.5%, fat 22.3%.

Parameter evaluated
Curcumin diet
Control diet
P value

Body wt
55.14 ± 2.95
54.25 ± 1.84
>;0.05

Blood glucose
264.3 ± 124
171.7 ± 32
=0.046

Hepatic Superoxide
74.08%
76.73%
>;0.5

Liver, % fat (400×)
26.5%
38.27%
<0.001

Liver histopathology
8.125
17.5
<0.001

Insulin, serum
2.14 ± 1.8
3.37 ± 0.84
=0.2

IL‐6, serum
2.83 ± 2.5
5.89 ± 4.8
=0.2

Adiponectin, serum
7.96 ± 3.54
13.43 ± 3.6
=0.04

TNFα, serum
5.7 ± 1.21
10.69 ± 4.02
=0.03

We conclude that dietary curcumin in OB/OB mice produces significant improvement in general liver health by reduction of % hepatic fat and histopathology, improved cytokine values and reduced tissue superoxide. An increase in blood glucose by this treatment remains unexplained.Funded: Sarah Morrison student grant (AN) & St. Luke's Foundation