bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Cardiovascular Autonomic Activity and Reactivity in Essential Hypertensive Patients after Yogic Practices
Authors: Khadka Rita , Paudel Bishnu Hari , Karki Prahlad
Published: June 2021

Globally prevalence of essential hypertension (EH) is increasing. It is one of the leading risk factors for global mortality. Several modifiable factors including overweight, obesity, physical inactivity contribute to the high prevalence rates of hypertension. Despite long‐term normalization of blood pressure by anti‐hypertensive drugs, there exists autonomic dysfunction. It is reported that yogic practices decrease BMI, BP and modify other risk factors in EH patients. We aimed to study whether combined easy yogic practices improve cardiovascular autonomic regulation both activity and reactivity in EH patients. Fifty essential hypertensive patients on similar pharmacotherapy were randomized into yoga (n=25, age 46.73±7.72 years) and control (n=25, age 46.1±7.01 years) groups. Yoga group practiced meditation, pranayama and few easy asanas for 40 min/day for one month. Control group did not practice yoga or any relaxation procedures. In both the groups cardiac autonomic activity was assessed using short‐term heart rate variability (HRV) by both time domain and spectral analysis, and reactivity using deep breathing (DBT), Valsalva Maneuver (VM), Handgrip (HGT) and Lying to standing (LST) tests before start of the study and after one month of the study. Institutional Ethical Committee approved the study. Age, BMI, BP, HR, and respiratory rate were comparable between both the groups before start of the study. The SBP (135.42 ± 15.5 vs 125.85 ±14.68, p=0.044), DBP (98.28 ± 12.95 vs 82.85 ± 10.09, p=0.019) and BMI (25.97 ± 2.96 vs 24.87 ± 2.70, p=0.039) decreased in yoga group after one month of yoga practice. Time domain measures of HRV, which are markers of cardiac parasympathetic activity [SDNN: 26.8(18.33.3) vs 35.2(26.87–38.3) ms, p=0.013; rMSSD: 25.2(8.95–33.3) vs 38.2(29.0–68.97) ms, p=0.024] increased in yoga group after yoga practice. Similarly, in spectral analysis, HF power [210(115.75–352.0) vs 400(141.0–518.25) ms2, p=0.0 46; Total power: 650.5(227.75–863.0) vs 862(634.5–1317), p=0.006] were increased in yoga group after yoga practice, whereas, there were no significant changes in markers of sympathetic activity; LF nu and LF/HF ratio after yoga practice. The E:I ratio (1.18 ± 0.08 vs 1.26 ± 0.09, p=0.003) and Valsalva ratio, which are indicators of parasympathetic reactivity also increased in yoga group after yoga practice. In conclusion, both parasympathetic activity and reactivity increased in EH patients after a month of yoga practice. It indicates that combined easy yoga practices improve cardiovascular autonomic regulation by increasing cardiac parasympathetic activity.

Support or Funding Information

BPKIHS Research grant

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 PREVIOUS EXERCISE TRAINING ON PLASMA AND TISSUE NITRITE, AND CARDIOVASCULAR PARAMETERS IN RATS WITH PARKINSONISM INDUCED BY 6‐OHDA
Authors: Martins‐Pinge Marli Cardoso , de Jager Lorena , Amorim Eric Diego Turossi , Lucchetti Bruno Fernando Cruz , Lopes Fernanda Novi Cortegoso , Crestani Carlos Cesar , Pinge‐Filho Phileno
Published: June 2021

In Parkinson's disease (PD) in addition to motor symptoms, presents cardiovascular dysfunctions, such as postural hypotension and blood pressure lability. Studies have shown that physical exercise decreases the risk of developing PD, as well as slows its progression. During aerobic training, there is an increase in the peripheral production of nitric oxide (NO), as well as in then substantia nigra pars compacta (SNpc) of patients with PD. However, no study evaluating the effects of exercise on NO levels of PD and the alterations on mean arterial pressure (MAP) and heart rate (HR) after inhibition of NO synthase (NOS) by Nw‐nitro‐arginine‐methyl‐ester (L‐NAME) in animals submitted to prior physical training and induced parkinsonism with 6‐hydroxydopamine (6‐OHDA) have been performed. Trained (T) or sedentary (S) animals underwent stereotactic surgery for bilateral 6‐OHDA or vehicle microinfusion (Sham group) in the SNPc. After 6 days, the animals were catheterized (artery and vein) to record the baseline parameters, followed by inhibition of NOS by L‐NAME (10mg/kg). A nitrite dosage was performed in the aorta, heart and plasma. After 4 weeks of swimming, there was resting bradycardia in the trained groups (6‐OHDA T and Sham T) (p <0.05). There was no difference in the NO from plasma in the four groups. In the aorta, there was an increase of NO in the 6‐OHDA group (p <0.05) when compared to Sham S, and a decrease in 6‐OHDA T animals (p <0.05) when compared to 6‐OHDA S and Sham T. At the heart, there was an increase in NO in the Sham T in relation to the sedentary ones and a decrease of NO in the animals 6‐OHDA T in relation to Sham T (p <0.05). Administration of L‐NAME promoted an increase in MAP and a decrease in HR in all groups, presenting lower increases in MAP in 6‐OHDA animals. In the FC, the difference between groups was a consequence of physical training. The data suggest the involvement of different NOS isoforms on cardiovascular system activated after physical training and Parkinsonism by 6‐OHDA.

Support or Funding Information

Capes (fellowship to Lorena de Jager)

CNPq (Research fellowships to MCMP, CCC, and PPF)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ventricular‐arterial Coupling in Prostate Cancer Patients Treated with Androgen Deprivation Therapy at Rest and During Exercise
Authors: Lovoy Garrett M. , Post Hunter K. , Banister Heather R. , Sutterfield Shelbi L. , Caldwell Jacob T. , Ade Carl J.
Published: June 2021

Introduction

Androgen‐deprivation therapy (ADT) in prostate cancer has been suggested to promote an unfavorable cardiovascular disease risk profile and long‐term cardiovascular mortality. Impairments in vascular structure (increased arterial stiffness) and function (decreased endothelial‐dependent dilation) are known to occur with ADT, however, it remains unknown if the changes in structure‐function relationship adversely impacts the interaction between ventricular and arterial systems. Ventricular‐arterial coupling is a measure of effective arterial elastance (Ea) and left ventricular end‐systolic elastance (Ees) and is a central determinant of cardiovascular performance and cardiac energetics. Therefore, this study sought to evaluate ventricular‐arterial coupling at rest and during submaximal exercise in prostate cancer patients with and without a history of ADT.

Methods

To date, 7 prostate cancer patients with (n=3) and without (n=4) a history of androgen‐deprivation therapy treatment have completed the study. Ea, Ees, and ventricular‐arterial coupling (Ea/Ees) were measured at rest and during supine submaximal exercise. A high Ea/Ees is reflective of a compromised interaction between ventricular and arterial systems. To minimize the effect of heart rate on each parameter submaximal exercise was performed at a work rate corresponding to a heart rate of 100 beats/min.

Results

At rest Ea (ADT: 2.9±0.2 mmHg/mL; non‐ADT: 3.4±0.8 mmHg/mL; P=0.2), Ees (ADT: 3.2±1.9 mmHg/mL; non‐ADT: 3.6±0.6 mmHg/mL; P=0.2), and Ea/Ees (ADT: 0.79±0.39; non‐ADT: 0.97±0.30; P=0.5) were similar between ADT and non‐ADT groups. Ea was not different between groups during exercise (ADT: 7.0±1.1 mmHg/mL; non‐ADT: 6.6±0.6 mmHg/mL; P=0.3). Moderate‐intensity exercise‐induced increases in Ees trended to be decreased in the ADT group (ADT: 3.5±1.2 mmHg/mL; non‐ADT: 4.7±0.5 mmHg/mL; P=0.05). Ea/Ees was also higher in the ADT group during exercise compared to the non‐ADT group, but did not reach statistical significance (ADT: 0.93±0.16; non‐ADT: 0.77±0.16; P=0.1).

Conclusions

The findings from this study provide preliminary data that indicates ADT in prostate cancer patients may adversely alter left ventricular end‐systolic elastance during exercise, but does not significantly alter ventricular‐arterial coupling. Additional data will contribute to the evaluation of the interaction between ventricular and arterial systems in patients receiving ADT.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
VO2max Can Be Accurately Predicted in American Football Athletes from Treadmill Exercise Time
Authors: Crouse Stephen F. , Tolson Homer , Martin Steven E. , Green John S. , Bramhall J P. , Hedrick Phil , Lytle Jason R.
Published: June 2021

Introduction

Prediction models for estimating maximal oxygen uptake (VO2max) from treadmill exercise time are lacking for American‐style football (ASF) athletes. Models developed from non‐athletes have not been tested in ASF players.

Purpose

We proposed to develop a model to estimate VO2max from exercise treadmill time in ASF athletes, and compare our Football model against the Foster (AHJ, 1984) and Bruce (AHJ, 1973) prediction equations.

Methods

Between 2003 and 2017, 472 collegiate ASF athletes (age 18 ± 1 yr, height = 186.1 ± 8.2 cm, weight 101.8 ± 20.4 kg) underwent treadmill exercise to maximal voluntary exhaustion (Bruce protocol) with VO2 measured (M‐VO2max) by means of an automated metabolic gas analysis system. Treadmill exercise time in minutes (T), as used in the Foster and Bruce equations, was used to predict M‐VO2max. For cross‐validation purposes, the 472 participants were randomly divided into Validation and Cross‐validation groups, n=236 for each group, using a random number generator. Linear regression was used to identify the predictive power (r2) in both groups. Independent t‐tests (with a Bonferroni adjusted α) and repeated measures ANOVA were used to test for differences between the two groups, and for differences among M‐VO2max, Foster, Bruce, and our Football estimates of VO2max. An α = 0.05 was used for all statistical tests.

Results

The Validation and Cross‐validation groups were not statistically different on any variable measured (p range = 0.454 to 0.941). Equations to estimate VO2max (mlO2.kg−1.min−1) were: Validation group VO2max = 4.012 * T −4.628 (r2 = .678, .001, SEE=4.07); Cross‐validation group VO2max = 4.025 * T – 4.693 (r2 = .661, .001, SEE‐4.16). These equations had a cross‐validation coefficient = 0.813 and a double cross‐validation coefficient = 0.823. Since no measured variables were different between the two validation groups, all athletes were combined to yield our final prediction equation: Football VO2max = 4.017 * T – 4.644 (r2 = 0.670, .001, SEE = 4.11). Estimated Football VO2max was not different from M‐VO2max (mean difference −0.002, p = 0.989). Foster and Bruce VO2max estimates were significantly different from M‐VO2max (mean difference −0.975, p = 0.001 and 1.995, p = 0.001, respectively) and from Football VO2max (p = 0.001).

Conclusion

VO2max of collegiate ASF athletes can be accurately estimated by our Football prediction equation using maximal treadmill exercise time as the predictor variable.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessment of Activity Monitor Placement During Free‐Living Conditions
Authors: Molesky Monroe J. , Vusich John , Montoye Alexander HK.
Published: June 2021

Despite the popularity of consumer‐based physical activity monitors (AMs), many of these AMs have little data examining their comparability when worn on different body locations.

PURPOSE

Our study's purpose was to determine placement‐related differences of a popularly available AM for estimating steps, Calories (kcals), distance traveled, active minutes, and sleep time in a free‐living setting.

METHODS

Participants (n=48) aged 18–28 years completed an unstructured, free‐living protocol in which participants wore two identical AMs (the Fitbit Flex or Fitbit Flex2), one on the non‐dominant (ND) wrist and one on the dominant (D) wrist, for five days. Participants were given the AMs early Monday morning and then instructed to return them Friday afternoon. Participants were instructed to wear the AMs 24 hours per day during all of their regular daily activities excluding contact sports and water‐based activities. Data were averaged across the three full days (Tuesday‐Thursday) and compared between wrists using paired t‐tests for each of the five recorded variables (steps, kcals, distance traveled, active minutes, and sleep time). Additionally, mean absolute difference (MAD) and mean absolute percent difference (MAPD) were calculated to assess differences between wrists.

RESULTS

The AMs had varied results in recording steps, kcals, distance traveled, active minutes, and sleep time in the comparison of the ND and D wrist locations. For all variables, estimates from the ND wrist were higher than the D wrist. AM step differences were significantly different with MAD of 664.7 steps/day (MAPD of 6.7%; p<0.001), kcals had an MAD of 53.4 kcals/day (MAPD of 2.1%; p<0.001), distance had MAD of 0.3 miles/day (MAPD of 6.8%; p<0.001), and active minutes had an MAD of 7.3 minutes/day (MAPD of 36.5%; p<0.001). Participant sleep duration trended toward statistical significance (p=0.22) with an MAD of 23.8 minutes/day (MAPD of 5.9%) between wrists.

CONCLUSION

Data collected from AMs placed on the ND and D wrists were not equivalent. While differences for some variables were relatively small, others were substantial. Caution is warranted when wearing AMs on different wrists despite the seemingly all purpose and multi‐locational nature of AMs. Future research should investigate other AM placements and optimum conditions for use.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Skeletal myofiber VEGF‐A‐targeted gene deletion induces mitochondrial, structural and contractile alterations in mouse diaphragm
Authors: Cannon Daniel T. , Rodewohl Lukas , Adams Volker , Breen Ellen C. , Bowen T Scott
Published: June 2021

Respiratory muscle weakness is a hallmark of COPD, heart failure, and critical illness. Vascular endothelial growth factor (VEGF) may be an important therapeutic target in chronic cardiopulmonary disease as it is essential for neovascularization and vessel repair following trauma. We hypothesized that respiratory muscle, which is required to persistently function, would exhibit impaired mitochondrial, structural, and contractile function in skeletal myofiber VEGF gene deleted mice.

We measured diaphragm biochemistry, structure, and contractile function in adult mice with conditional deletion of the VEGF‐A gene in skeletal myofibers (SkmVEGF−/−). Male SkmVEGF−/− mice (n=12) were compared to wild type (WT) controls (n=13) – both on a C57BL/6J background. Fiber bundles were isolated and electrically stimulated in vitro to evaluate force‐frequency and fatigue profiles. Mitochondrial O2 consumption and H2O2 flux (index of mitochondrial ROS) were simultaneously measured in saponin‐permeabilized fiber bundles (Oroboros, Innsbruck, AT). Fiber structure and biochemistry were measured using standard techniques (IHC, Western, ELISA).

Diaphragm VEGF protein was lower in SkmVEGF−/− than WT mice (1.5±0.2 vs. 3.0±0.4 pg/total protein, p<0.05). Compared to WT mice, the force‐frequency relationship was depressed in SkmVEGF−/− (F[7,161]=15.0, p<0.05), with maximal specific force reduced by ~10 % (24±1 vs. 21±1 N/cm2; p<0.05). However, fatigue resistance tended to be greater following SkmVEGF−/− (F[2,115]=3.3, p=0.06). Fiber type proportions were unchanged, but type I fiber cross‐sectional area was reduced in SkmVEGF−/− (653±45 vs 493±53 μm2; p<0.05). Compared to WT, sarcomeric actin protein expression was reduced by ~30% in SkmVEGF−/− (p<0.05) while myosin heavy chain, MAFbx, MuRF1, PGC1α, and HIF1α protein remained unchanged (p>0.05). Mitochondrial respiration was not different between SkmVEGF−/− and WT (F[1,80]=0.9, p>0.05) in each of the respiratory states. However, H2O2 flux was reduced in SkmVEGF−/− (F[1,75]=14.6, p<0.05).

Skeletal myofiber‐specific VEGF deletion contributed to diaphragm weakness, but tended to improve fatigue resistance in this highly oxidative muscle. Reductions in oxidative fiber size, sarcomeric actin protein content, and ROS generation following VEGF gene deletion may contribute to protecting mitochondrial respiratory function in the diaphragm. The adaptations may be part of compensatory mechanisms mitigating larger deficits in force generation and fatigue resistance.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
O‐GlcNAc Transferase is Required to Maintain Satellite Cell Viability
Authors: Daughtry Morgan , Geisler Hannah , Fisher Taylor , Luo Jing , Shi Hao , Gerrard David
Published: June 2021

O‐GlcNAcylation is the addition and removal of UDP‐GlcNAc to proteins by O‐GlcNAc transferase (OGT) and O‐GlcNAcase (OGA), respectively. This process functions as a nutrient sensing pathway because UDP‐GlcNAc, synthesized in the hexosamine biosynthetic pathway, fluctuates with nutrient levels available to the cell. Although previous studies have established the critical role of OGT in metabolism in a variety of cell types, the role of OGT in satellite cells (SCs) remains unknown. In this study, we generated SC‐specific OGT knock‐out (cKO) mice to investigate the functional role of OGT in SC homeostasis. Initially we subjected WT and cKO muscle to cardiotoxin‐induced injury to assess SC regenerative capacity during muscle regeneration. Compared to WT mice, the cKO mice experienced severely impaired regenerative myogenesis. To investigate whether OGT deficiency induced lack of regeneration was caused by changes in SC intrinsic properties, we traced SCs cycling and self‐renewal in vivo by monitoring the turnover rate of green fluorescent protein (GFP) intensity using a H2B‐GFP lineage tracing strategy. Flow cytometry analysis of the GFP labeling revealed that cKO SCs possessed a higher percentage of GFP‐retained subpopulation than WT SCs after a 10‐week chase period, indicating that SCs lacking OGT had impaired self‐renewal. We then assessed SC proliferative capacity in vitro using clone assay and observed SCs from cKO mice had significantly reduced clone size compared to their WT counterparts. Morphologically, cKO SCs exhibited larger cell size and increased complexity compared to WT SCs, suggesting the lack of proliferation may be caused by the impairment of SC's ability to divide. Taken together, our findings suggest that OGT, and thus O‐GlcNAc signaling, plays a critical role in SC self‐renewal, proliferation, and tissue repair through mediating nutrient sensitive cell division.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AMP Deaminase 3 Knockout Does Not Reduce Mitochondrial Content Loss in Denervation Induced Inactivity
Authors: Verhoeven Nicolas A. , Brault Jeffrey J.
Published: June 2021

Muscle atrophy leads to decrements in muscle function, partly attributable to reductions in mitochondrial content. One controller of mitochondrial content is AMP‐activated protein kinase (AMPK), which when bound by AMP stimulates PGC‐1α leading to mitochondrial biogenesis, keeping mitochondrial content elevated. AMP Deaminase 1 is the dominant isoform of AMPD in skeletal muscle, yet AMP Deaminase 3 (AMPD3) is robustly upregulated during atrophy conditions in skeletal muscle, and degrades AMP (AMP à IMP + NH3). The purpose of this study is to determine if loss of AMPD3 gene will reduce mitochondrial content loss typically seen with atrophy.

Methods

Whole body AMPD3 knock out mice on a C57BL6 strain background were surgically denervated on the left hind limb by removal of ~2 mm of the sciatic nerve. A sham surgery was performed on the right hind limb. Two weeks later, mice were weighed, and extensor digitorum longus (EDL) muscles were collected, weighed, and analyzed for citrate synthase enzyme activity as a measure of mitochondrial content. ANOVA analyses were made between three genotypes (Wild Type ‐ WT, AMPD3 heterozygous ‐ HET, and AMPD3 knockout ‐ KO) of 12 week old littermate female mice (n = 5–8).

Results

Body weights were not significantly different among genotypes (22.9 ± 0.7 g WT, 22.3 ± 0.4 HET, 22.0 ± 1.0 KO)(p = .74). Likewise, non‐denervated EDL muscle weights were not significantly different among genotypes (8.75 ± 0.2 mg WT, 8.47 ± 0.2 HET, 8.77 ± 0.3 KO)(p = 0.67). As expected, surgical denervation for two weeks led to substantial muscle atrophy versus innervated muscle (22.07 ± 1.42% WT, 23.69 ± 4.84 HET, 19.2 ± 3.67 KO), which was not different among genotypes (p = 0.68). Finally, citrate synthase activity in innervated EDL was not significantly different among genotypes (10.27 ± 0.36 WT, 9.3 ± 0.77 HET, 8.93 ± 0.38 KO)(p = 0.16). The decrease in citrate synthase activity due to denervation was not significantly different between wild type and heterozygous, but there was a trend for heterozygous group to have less activity (20.32 ± 2.02% WT, 4.38 ± 5.83 HET)(p = 0.059).

Conclusion

These data suggest AMPD3 does not affect mitochondrial content loss in this atrophy model. However, since AMPD3 was not present during development in our AMPD3 knockout mice, we cannot exclude compensation from other AMPD isoforms. Therefore, future research should investigate either inducible muscle specific AMPD3 knockouts or loss of both AMPD1 and AMPD3.

Support or Funding Information

NIH R01 AR 070200

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Heat Stroke Triggers Electrocardiographic (ECG) Abnormalities in a Conscious Rat Model
Authors: Mayer Thomas Andrew , Leon Lisa
Published: June 2021

Heat stroke (HS) is a potentially fatal injury that affects thousands of individuals every year. Multiple organs, including the heart, may be damaged as a result of HS. We showed previously that HS rats exhibit tachycardia, elevated cardiac Troponin I, and histological cardiac damage. Several observational studies and numerous case reports have described electrocardiogram (ECG) abnormalities among human HS patients, but these abnormalities have not been thoroughly investigated in animal HS models. This study identified the type of ECG abnormalities elicited in HS rats. Adult male Fisher 344 rats weighing 278.1±3.9 grams were previously implanted with radiotelemetry for continuous recording of core temperature (Tc), heart rate (HR), blood pressure, and Lead II ECG. After surgical recovery, rats were passively heated at an ambient temperature of 39°C until Tc reached 42.0±0.1°C (TcMax). Injury severity was classified as mild, moderate, or severe based on Tc responses during 24‐h of recovery. Baseline ECG recordings prior to heat exposure were normal. Severe and moderate rats had higher HR than mild rats at TcMax (mild 567±5; moderate 608±4; severe 611±15 bpm; p<0.05). Amplitude of the R wave during 1‐h of recovery was less for severe than mild and moderate rats (mild 1.58±0.12; moderate 1.60±0.10; severe 1.20±0.11 mV; p<0.05). ST depression was frequently observed prior to and shortly after TcMax and worsened with increasing injury severity. ST elevation was noted in two severe rats. ECG recordings taken the day after HS demonstrated an absence of T waves among severe rats and some moderate rats. These results demonstrate that ECG abnormalities occur as HS injury progresses and persist throughout acute recovery, which may be indicative of damage or dysfunction of the heart. Importantly, two rats died within 24‐h of HS recovery; one had extensive morphological ECG alterations whereas the other had a normal ECG, suggesting that cardiovascular dysfunction does not solely determine mortality but may contribute. In conclusion, ECG recordings should be monitored after HS for assessment of injury severity and potential cardiovascular dysfunction. Author views are not official US Army or DoD policy.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blocking Peripheral Beta‐Adrenergic Receptors Reduces Induction of Skeletal Muscle Thermogenesis
Authors: Gorrell Erin , Mull Sarah , Novak Colleen
Published: June 2021

Obesity is a worldwide trend that is cause for concern due to its detrimental effects on numerous health factors and increased risk of mortality. The propensity for obesity, although influenced by diet, is also worsened by sedentary lifestyle. Indeed, individuals' daily activity levels and activity energy expenditure predict weight gain and obesity. Increased energy expenditure, whether deliberate or spontaneous, is associated with leanness and reduced risk for obesity. With respect to increasing energy expenditure through thermogenesis, previous investigation has focused largely on browning of white adipose and brown adipose tissue thermogenesis, with much less attention paid to mechanisms mediating thermogenesis in skeletal muscle. Here, we investigated the effects of contextually induced muscle thermogenesis in rats through exposure to predator odor in rats. We hypothesize that thermogenesis in skeletal muscle is mediated by the sympathetic nervous system (SNS), specifically through activation of muscle β‐adrenergic receptors. To test this, we examined the effects of nadolol, a peripherally acting β‐adrenergic antagonist, on predator odor‐induced thermogenesis. IPTT‐300 transponders from Bio Medic Data Systems were surgically implanted in the left and right gastrocnemius muscles of male rats (N=13). Rats were exposed to each of four conditions (2×2): nadolol or saline vehicle, each with and without predator odor (1.5″×2″ towel with ferret odor) or control stimulus; muscle temperatures were measured over 120 minutes. Predator odor significantly induced muscle thermogenesis in vehicle‐treated animals. The mixed β‐adrenergic antagonist nadolol significantly reduced predator odor‐induced thermogenesis. This demonstrates that predator odor‐induced skeletal muscle thermogenesis is mediated, at least in part, by β‐adrenergic receptor activation, likely stemming from sympathetic nerve activation. Our previous work has demonstrated that this thermogenic induction is accompanied by enhanced energy expenditure. With the focus on muscle, rather than adipose thermogenesis, we establish a pathway that expands the understanding of energy balance, its mechanisms, and possible treatments. Going forward, induction of muscle thermogenesis may be applied to the treatment of obesity.

Support or Funding Information

NIH NIDDK R15‐DK‐097644 and R15‐DK‐108668 to CMN

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kappa opioid receptor activation in the Preoptic Area (POA) contributes to the impairment of brown adipose tissue activation in rats on a high fat diet (HFD)
Authors: Madden Christopher J.
Published: June 2021

We have recently demonstrated that cold‐evoked activation of brown adipose tissue is inhibited in rats maintained on a high fat diet for at least eight weeks. Activation of neurons in the external lateral parabrachial nucleus is a necessary relay in the afferent pathway for cold‐evoked increases in BAT thermogenesis and BAT sympathetic nerve activity. In order to assess whether there was an impaired activation of the cold afferent pathway, the present study examined the expression of the immediate early gene, fos, in the external lateral parabrachial nucleus of cold exposed rats maintained on either a control diet or a HFD. Contrary to the hypothesis, there was no difference in HFD rats compared to control diet rats, in the number of neurons in the external lateral parabrachial nucleus which expressed fos in response to cold‐exposure. However, there was an increase in the number of neurons expressing fos in the dorsal lateral parabrachial nucleus (LPBd) of HFD rats compared to control diet rats. This is interesting since the LPBd is an area that has been shown to inhibit cold‐evoked activation of BAT SNA. Furthermore, many of the dorsal lateral parabrachial neurons that were activated in the HFD rats during cold exposure contained preprodynorphin. Preprodynorphin cells in the LPBd project to the preoptic area and can produce the kappa opioid receptor agonist dynorphin. These observations led to my hypothesis that activation of kappa opioid receptor (KOR) in the POA contributes to the inhibition of BAT thermogenesis during HFD. Therefore, the present study tested the hypothesis that selective blockade of KOR, in the POA would reverse the impairment of cooling‐evoked BAT SNA in HFD rats, but fail to increase BAT SNA in control diet rats. Nanoinjection of the KOR antagonist, norBNI, in the POA reversed the HFD‐induced impairment of cold evoked BAT SNA and thermogenesis. In contrast, injection of norBNI in rats on a control diet did not increase BAT SNA or BAT thermogenesis. These data suggest that there is an aberrant activation of a dynorphin input from the LPBd to the POA in rats on a high fat diet. Activation of this pathway in HFD‐induced obesity may help to explain the weight reducing effects of KOR antagonists such as naltrexone.

Support or Funding Information

1 R01 DK112198‐01A1

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Mobility Group Box 1 Neutralization in the Brain Prevents Inflammation, Sympathoexcitation and Hypertension
Authors: Sriramula Srinivas , Nair Anand R. , Francis Joseph
Published: June 2021

High mobility group box 1 (HMGB1) is a nuclear protein, that once translocated to cytoplasm, can act as a chemoattractant and a proinflammatory mediator. Post‐translationally modified HMGB1 can interact with different receptors, such as toll‐like receptor 4 (TLR4) and chemokine receptor CXC receptor 4 (CXCR4), to induce acute and chronic inflammation. We have previously showed that central TLR4 blockade delayed progression of hypertension and improved cardiac function. However, the involvement of HMGB1 and its interaction with TLR4 in the pathogenesis of hypertension has not been fully explored. Therefore, in this study, we investigated the role of HMGB1 in mediating hypertension, inflammation and sympathoexcitation. We hypothesized that blockade of HMGB1 prevents the development of hypertension. Chronic angiotensin II (AngII) infusion (200 ng/kg/min, SC, 14 days) significantly increased mean arterial pressure (telemetry) in male Sprague‐Dawley rats compared to saline‐infused controls (163 ±5 vs. 105 ±4 mmHg, n=7, p<0.01). AngII‐infusion significantly increased HMGB1 levels in the plasma (21 ±3 vs.15 ±2 ng/ml, p<0.01) and cerebrospinal fluid (34±3 vs. 21±1 ng/ml, p<0.01), and elevated HMGB1 protein expression (2.5 fold, n=6, p<0.01 vs. Control) in the brain hypothalamic paraventricular nucleus (PVN). Intracerebroventricular infusion of neutralizing monoclonal anti‐HMGB1 antibody (10 μg/kg/day) attenuated AngII‐induced hypertension (120 ±2 mmHg, p<0.01 vs. AngII). Furthermore, AngII‐infusion significantly increased expression of TNF, IL‐1, IL‐6, TLR4, CXCR4, and NF‐kB in the PVN, which was prevented by HMGB1 neutralization. AngII infusion resulted in sympathoexcitation, as indicated by increased plasma norepinephrine levels (1602 ±53 vs. 549 ±25 pg/ml, P<0.01 vs. Control), but this increase was blunted by HMGB1 neutralization (720 ±25 pg/ml, P<0.05 vs. AngII). Taken together, these data suggest that neutralization of HMGB1 in the brain reduces inflammation and decreases sympathoexcitation, thereby preventing the development of AngII‐induced hypertension.

Support or Funding Information

The American Heart Association, 15SDG25720021 (SS), 16GRNT30510012 (JF)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Carotid Body in Doxorubicin‐induced Heart Failure
Authors: Arnold Alexandre José Tavolari , Jensen Leonardo , Souza Leandro E. , Silva Maikon B. , Santos Fernando , Moraes‐Silva Ivana C. , Irigoyen Maria‐Claudia
Published: June 2021

Doxorubicin (DOX) cardiotoxic effects may lead to heart failure, a condition of high morbidity and mortality characterized by a marked sympathetic hyperactivity. Currently, evidences show that carotid corpuscle (CC) denervation can be a therapeutic approach in cardiac diseases due to the possibility of reducing this sympathetic overactivity. Therefore, we aimed to investigate whether CC denervation can attenuate autonomic and cardiac dysfunctions induced by DOX in rats.

Methods

After ethical committee approval (4412/16/07), male Wistar rats were divided in: Control (C; n=11), DOX (D; n=5) and DOX+CC denervation (DD; n=7). DOX was administered 6 times by i.p. injections every 4 days reaching a total dose of 2.5mg/kg. After 10 days of the last dose of DOX, the animals were evaluated by echocardiogram and prepared for the recording of direct blood pressure signals. Autonomic modulation was studied by spectral analysis. Results are expressed as mean±SEM; p <0.05.

Results

Both D and DD rats presented heart rate increase vs. C (C=312 ± 3.6; D=408 ± 16.5; DD=430 ± 25.6 bpm) without blood pressure changes. Elevated sympathetic modulation was confirmed in both D and DD rats vs. C by the increase in the LF (low frequency) component of heart rate (C = 14.27 2.0; D=32.50 ± 2.6; DD=27.7±2.7 n.u.), and an increase in sympathovagal balance (C=0.19±0.03; D=0.53±0.07; DD=0.42±0.07). Reduction in the vagal modulation, expressed by the HF (high frequency) component, was also seen in DD and D rats (C=85,7±2.0; D=67.5±2.6; DD=72.29 ± 2.7 n.u.) together with a decrease in baroreflex gain higher than 50% in these groups vs. C. D and DD groups reduced diastolic left ventricle diameter (C=9.22±0.4 mm; D=8.93±0.2 mm; DD=7.96±0.2 mm) and volume (C=710.6 ± 2.0; D=378.01 ± 1.5; DD=407.13 ± 16.00 uL). Diastolic dysfunction in DD group was evidenced by the increase in isovolumetric relaxation time (C=22.27±1.61; D=23.25±1.47; DD=30.64±1.78 ms) and E/E′ relation (C=13.0 ± 2.3; D=15.19 ± 2,0; DD=34.83 ± 2.19), and by the decrease in E′/A′ ratio in both D and DD groups (C=1.64±0.1; D=0.73±0.1; DD=0.54±0.05). DD also presented systolic dysfunction in relation to C and D rats, evidenced by a decrease in both ejection fraction (C=79.19±3.35; D=76.55±6.95; DD=53.90±3.35 %) and fractional area change (C=62.03±5.5; D=57.45±2.5; DD=43.18±3.6 %).

Conclusion

CC denervation did not alter the autonomic dysfunction induced by DOX; however, it was more deleterious to cardiac function. In this early phase (10 days) of DOX‐induced heart failure time course, sympathetic modulation may compensate the cardiac maldaptations, thus CC integrity played a key role.

Support or Funding Information

CNPq 467300/2014‐3

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence for a circulating factor released by the brain that contributes to chronic antidiabetic actions of leptin
Authors: do Carmo Jussara M. , da Silva Alexandre A. , Hall John E.
Published: June 2021

We previously demonstrated that leptin has powerful central nervous system (CNS)‐mediated antidiabetic actions that are independent of the autonomic nervous system (ANS) and the pituitary. In this study, we examined if a circulating factor released by the brain contributes to leptin's chronic antidiabetic actions in insulin deficient rats. Male inbred 4‐week‐old Lewis rats (n=14) were conjoined by attaching their skin to allow shared circulation. Six weeks later, the rats were implanted with an intracerebroventricular (ICV) cannula into the lateral ventricle to infuse leptin in one rat and vehicle in the other rat of each pair. Eight days after surgery, food intake, body weight and blood glucose concentration were measured for 5 consecutive days and then streptozotocin (STZ) was injected (40 mg/kg) to induce insulin‐deficient diabetes in both rats. Five days after STZ injection, leptin (15 mg/day) or vehicle (0.5 ml/h) was delivered ICV continuously for 7 days via osmotic minipumps. STZ injection significantly increased average blood glucose concentration (359±19 vs. 79±6 mg/dL) and food intake (49±2 vs. 39±3 g/day). Despite higher food intake, average body weight decreased after STZ injection (619±23 vs. 664±23 g). Chronic ICV leptin infusion restored normoglycemia (110±31 vs. 359±19 mg/dL) in leptin‐treated rats and reduced blood glucose by ~27% in the paired parabiotic rat infused with vehicle (269±20 vs. 366±41 mg/dL). Leptin treatment did not reduce food intake (53±20 vs. 49±23 g/day) or body weight (619±23 vs. 610±20 g) in the paired rats. After stopping leptin treatment, blood glucose concentration returned to diabetic values in leptin‐treated (305±44 vs. 110±31 mg/dL) as well as in vehicle‐treated rats (330±11 vs. 269±20 mg/dL), and food intake increased 37% (67±5 vs. 49±3 g/day). These results suggest that the chronic antidiabetic effects of leptin may involve release into the systemic circulation of a brain‐derived neuroendocrine factor that enhances glucose homeostasis in insulin deficient rats. (NHLBI‐PO1HL51971, NIGMS P20GM104357)

Support or Funding Information

Department of Physiology and Biophysics and Mississippi Center for Obesity Research. University of Mississippi Medical Center.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cats increase lean body mass with carnitine or carnosine but not with the combination
Authors: Jewell Dennis E. , Panickar KIran S.
Published: June 2021

This study evaluated whether dietary carnitine or carnosine would change lean body mass, circulating cytokines or metabolites in cats. All study protocols were reviewed and approved by the Institutional Animal Care and Use Committee, Hill's Pet Nutrition, Inc., Topeka, KS. Forty four pets were assigned into four groups: Group 1 (n=11) was fed the control diet, group 2 (n=11) was fed the control diet + L‐carnitine (0.03%), group 3 (n=12) was fed the control diet + L‐carnosine (0.1%), and Group 4 (n=10) was fed the Control diet + L‐carnitine + L‐carnosine. The ages of the cats ranged from 7.2 to 13.9 yr. The duration of the study was 6 months. Initial body composition, cytokines and metabolomics profiles were compared to final and changes were compared across treatments. Metabolomics were measured by Metabolon (Morrisville, NC), cytokines were measured by ELISA. Change in lean body mass (LBM) was assessed by Dual‐energy X‐ray absorptiometry (DEXA) and reported in cats as the difference in LBM between initial and final times. Changes in analytes were then compared amongst the 4 groups. Serum levels of cytokines assessed included Flt‐3L, IFN‐γ, IL12p40, IL‐4, IL‐6, IL‐8, IL‐13, IL‐18, and MCP‐1. Modest reductions were observed in the levels of selected cytokines on day 169 when compared to the baseline but these changes were not significant between groups. Lean body mass results showed that cats fed either carnitine alone (+106 g) or carnosine alone (+96 g) had increased lean when compared to control cats or cats supplemented with both carnitine and carnosine (p<0.01). There was no statistical difference between treatments in either body weight or body fat change. Carnitine and deoxycarnitine were increased in the group that had carnitine alone (p<0.05) while many acyl carnitines were increased in both groups supplemented with carnitine. Carnosine was not changed but beta‐alanine was increased in cats fed carnosine. The metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan and dietary polyphenolic compounds) occurs, in part, through the involvement of enzymes encoded within the microbiome. Several microbiota‐derived‐metabolites were higher in Groups 2, 3, and 4 when compared to Group 1 at various time points. These data indicate that supplementation of carnitine or carnosine is beneficial in increasing LBM in felines but that when combined they do not influence LBM.

Support or Funding Information

This study was funded by Hill's Pet Nutrition Inc.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hydroxylated Metabolites of Common Airborne Polychlorinated Biphenyls and Their Potential for Disrupting Estrogen Homeostasis and Adipogenesis
Authors: Parker Victoria S. , Squirewell Edwin , Joachim‐Lehmler Hans , Robertson Larry W. , Klingelhutz Aloysius , Duffel Michael W.
Published: June 2021

Endocrine disruption, metabolic syndrome, diabetes, cancer, and other diseases have been associated with exposure to polychlorinated biphenyls. There is a growing interest in the lower chlorinated PCBs due to their presence in the indoor air of older buildings, their susceptibility to metabolism catalyzed by cytochrome P450 to form hydroxylated PCBs (OH‐PCBs), and their potential to disrupt endocrine function. OH‐PCBs are further metabolized in reactions catalyzed by cytosolic sulfotransferases (SULTs) to form PCB‐sulfates. Estrogen sulfotransferase (SULT1E1) is important in the regulation of cellular levels of active and inactive estrogens, with estradiol being a primary physiological substrate. Recent literature has suggested that decreased activity of SULT1E1 can impact adipocyte differentiation. We hypothesize that some lower‐chlorinated OH‐PCBs potently inhibit SULT1E1 causing increased cellular levels of estradiol and a decrease in human adipocyte differentiation. Our studies using purified recombinant human SULT1E1 (at 7.0 nM estradiol) found 4‐OH‐PCB 11 and 4′‐OH‐PCB 25 to be potent inhibitors, with IC50 values of 7.2 and 7.3 nM, respectively. 4′‐OH‐PCB 8 and 4‐OH PCB 52 inhibited SULT1E1 with IC50 values of 17.6 and 18.6 nM, respectively, and the least potent inhibitor, 4′‐OH‐PCB 3, had an IC50 of 1300 nM. We have exposed immortalized human adipocytes to these five OH‐PCBs and another known inhibitor of SULT1E1, triclosan, at concentrations of 1 uM and 10 uM for 72 hours followed by differentiation for 11 days. The cells were stained with AdipoRed to quantitate lipid accumulation. Exposure to 4′‐OH‐PCB 3 resulted in no significant reduction in lipid accumulation, while the remaining OH‐PCBs and triclosan showed significant reductions in adipocyte differentiation. This congener‐selective ability to inhibit SULT1E1 and adipocyte differentiation is consistent with the hypothesis that OH‐PCB‐mediated inhibition of SULT1E1 can inhibit human adipogenesis. Future studies will explore the role of this inhibition of SULT1E1 in adipogenesis by measuring mRNA expression of SULT1E1 and prominent adipogenic markers in these cells as well as cellular levels of estradiol and estradiol‐sulfate.

Support or Funding Information

Supported by NIH grants P42 ES013661 and R25 GM058939, and a William Townsend Porter Fellowship from the American Physiological Society.

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 role of ACE2/Ang 1–7/Mas axis in the white adipose tissue for the prevention of obesity and insulin resistance through aerobic exercise training
Authors: Américo Anna Laura Viacava , Muller Cynthia Rodrigues , Fonseca‐Alaniz Miriam Helena , Evangelista Fabiana Sant'Anna
Published: June 2021

The activation of angiotensin converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang 1–7)/receptor Mas axis has been associated with cardiovascular and metabolic improvement, and may represent a new therapeutic target for cardiometabolic diseases. Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). In the present study we evaluated if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1–7)/Mas axis in the white adipose tissue (WAT). Adult male C57BL6/J mice were assigned into chow‐fed controls (C, n=5), chow‐fed trained (T, n=5), cafeteria diet (CAF, n=5), and cafeteria diet plus trained (CAFT, n=5). AET was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (#002/15). The body weight of the T and CAFT groups were lower from the third week of experimental protocol compared to C. The CAF group had higher retroperitoneal and subcutaneous (SC) fat pads weights compared to C, but the AET was able to prevent these increases in the CAFT group. Periepididimal (PE) fat pad weight was lower in T group compared to other groups. Cafeteria diet induced glucose intolerance and IR in CAF group (AUC: 35200± 1076 mg/dL/120 min; kITT: 2.5 ± 0.17 %/min) compared to the C group (AUC: 28333±1305 mg/dL/120 min; kITT: 3.7 ± 0.21 %/min), which were counteracted by AET in CAFT group (AUC: 28896 ± 1133 mg/dL/120 min; kITT: 3.9 ± 0.33 %/min). In the PE‐WAT, the activity of ACE2 was higher in CAF and CAFT groups compared to C and T groups, but Ang 1–7 concentration and Mas protein expression were not different among groups. In the SC‐WAT, no differences were found in ACE2 activity and Mas protein expression, but the Ang 1–7 concentration was lower in CAF and CAFT compared to C and T groups. In conclusion, the prevention of obesity and IR by AET was independent of the ACE2/Ang 1–7/Mas axis activation in the visceral and subcutaneous WAT.

Support or Funding Information

Support: FAPESP #2015/04948‐4; #2016/23783‐9.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.