bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle metaboreflex modulation of post‐exercise heart rate kinetics
Authors: Tomczak Corey R , Rapin Nicole , Lahti Dana , Boyes Natasha G
Published: June 2021

A delay in the post‐exercise recovery heart rate is a strong predictor of mortality that may be mediated by autonomic nervous system dysfunction (e.g., impaired parasympathetic reactivation and/or augmented sympathetic nerve activity, SNA). We tested the hypothesis that augmented SNA during exercise recovery would delay the rate of post‐exercise heart rate decay compared to a control condition (CTL). Twenty‐two healthy adults (13 f; 22 ± 2 yrs; peak VO2 = 47 ± 7.4 mL/kg/min; BMI = 23.4 kg/m2) performed heavy‐intensity exercise above the ventilatory threshold at 90 ± 6% peak heart rate for 5 min during CTL (no SNA augmentation) and during an experimental (EXP) condition. The EXP condition entailed SNA augmentation via the muscle metaboreflex following 2 min of bilateral isometric handgrip exercise at 30–40% maximal voluntary contraction during cycle ergometry exercise. Bilateral circulatory occlusion was performed during the last 1 min of exercise and continued during 4 min of recovery. Post‐exercise heart rate kinetics were analyzed using paired t‐tests and significant differences were determined when P < 0.05. There was no difference in end‐exercise heart rate (last 1 min) between CTL (159 ± 3 beats/min) and EXP (158 ± 3 beats/min, P = 0.592), amplitude of heart rate recovery between CTL (−61 ± 2 beats/min) and EXP (−64 ± 2 beats/min, P = 0.178), or end recovery heart rate between CTL (98 ± 3 beats/min) and EXP (94 ± 3 beats/min, P = 0.068). There was a significant difference in heart rate kinetics between CTL (57 ± 3 s) and EXP (69 ± 5 s, P = 0.009). These findings suggest that augmented SNA may modulate a delay in the recovery time for heart rate following heavy intensity exercise.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Parents exacerbated fructose intake causes early cardiovascular autonomic dysfunctions in offspring
Authors: dos Santos Camila Paixão , Silva Deiwet Ribeiro , Da Silva Dias Danielle , Araujo Amanda , Bernardes Nathalia , Conti Filipe Fernardes , Irigoyen Maria Cláudia , De Angelis Kátia
Published: June 2021

The aim this study was to evaluate the effects on birth weight and metabolic, hemodynamic and autonomic profiles in offspring of parents submitted to chronic fructose overload. The Fructose genitor group was formed by adult Wistar rats (males and females) that underwent a fructose overload (10%) in drinking water for 60 days. The Control genitor group was formed by adult Wistar rats (males and females) who were only followed for the same period receiving a standard diet. Mating was carried out and the females continued to receive the same diet (fructose or standard) during all gestation and lactation. The offspring were weighed on the day of birth; the day of birth of the offspring was considered the day 0 (zero) of the protocol. After weaning, offspring were divided into group C (descendants of control parents, n = 7) and group F (descendants of fructose parents, n = 7). The groups were evaluated 30 days after weaning. Metabolic parameters were measured with reagent strips. Blood pressure (BP) were recorded directly. Cardiovascular autonomic modulation was evaluated by spectral analysis. Birth weight was lower in F when compared to C group (5.82 ± 0.06 vs. C: 6.42 ± 0.06 g). Regarding metabolic evaluations, the glucose and triglycerides were similar between studied groups. The mean (C: 106 ± 2.7 vs. F: 110 ± 3.4 mmHg), systolic and diastolic BP and the heart rate were similar between the groups studied. However, the F group showed lower cardiac parasympathetic modulation than C group, evidenced by a reduction in cardiac high frequency band (F: 74.40 ± 3.36 vs. C: 88.20 ± 2.21 nu) and higher cardiac sympathetic modulation (F: 25.60 ± 3.36 vs. C: 11.80 ± 2.21). Additionally, the F group showed increase in the sympatho‐vagal balance compared to the C group (0.37 ± 0.06 vs. C: 0.14 ± 0.03). Moreover, higher vascular sympathetic modulation, evidenced by increase of the low frequency band (F: 5.64 ± 1.17 vs. C: 2.25 ± 0.49 mmHg²), was observed in F in relation to C group. In conclusion, offspring of parents submitted to fructose overload present low birth weight and early cardiovascular autonomic dysfunction in adult life. These findings suggest that the inadequate consumption of fructose from the parents may be associated with the onset of cardiovascular disease in offspring in adult life.

Support or Funding Information

FAPESP (2018/17183‐4); CAPES, CNPq.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Angiotensin‐(1‐7) Attenuates Blood Pressure and Cardiac Hypertrophy in Aged Mice
Authors: Miller Amanda J. , Bingaman Sarah S. , White Melissa , Arnold Amy C.
Published: June 2021

Background

Aging is associated with an increase in blood pressure, which is attributed to multiple factors including endothelial dysfunction, cardiac hypertrophy, and changes in cardiovascular autonomic regulation including increased sympathetic tone and reduced measures of parasympathetic tone. In addition, altered responsiveness of the renin‐angiotensin hormone angiotensin (Ang) II has been implicated in age‐related cardiovascular risk. The deleterious actions of Ang II are generally opposed by the vasodilatory and cardioprotective hormone Ang‐(1‐7); however, to our knowledge no studies have evaluated the importance of Ang‐(1‐7) to blood pressure regulation during aging. In this study, we hypothesized that Ang‐(1‐7) would improve blood pressure and cardiac autonomic control in healthy aged mice.

Methods

Sixteen month‐old male C57BL/6J mice received 6‐week Ang‐(1‐7) [400 ng/kg/min, n=5] or saline infusion (n=3) via subcutaneous osmotic mini‐pumps. All mice were fed standard chow diet (18% kcal from fat). Blood pressure was measured during the last week of treatment via a carotid artery catheter connected to a strain‐gauge transducer and blood pressure analyzer. Cardiac sympathetic and parasympathetic tone and sympathovagal balance were calculated from the blood pressure signal using spectral analysis frequency domain methods. Heart weight and the heart: body weight ratio was determined at end of experiments.

Results

Ang‐(1‐7) significantly decreased systolic [Ang‐(1‐7): 102±1 mmHg, saline: 112±6 mmHg, P=0.050] diastolic [Ang‐(1‐7): 78±2 mmHg, saline: 85±2 mmHg, P=0.033], and mean [Ang‐(1‐7): 86±2 mmHg, 94±3 mmHg, P=0.029] blood pressure in aged mice. The blood pressure‐lowering effect of Ang‐(1‐7) was associated with a trend towards reduced sympathetic tone [Ang‐(1‐7): 0.17±0.06, saline: 0.29±0.03, P=0.081], with no effect on vagal tone [Ang‐(1‐7): 0.25±0.11, saline: 0.17±0.06, P=0.625]. Furthermore, Ang‐(1‐7) reduced heart weight [Ang‐(1‐7): 0.19±0.01 g; saline: 0.23±0.02 g, P=0.044] and the heart to body weight ratio [Ang‐(1‐7): 0.004±0.001; saline: 0.006±0.001, P=0.022]. There was no effect of Ang‐(1‐7) on body weight or composition (P > 0.2).

Conclusions

Chronic Ang‐(1‐7) treatment lowers blood pressure and attenuates cardiac hypertrophy in aged mice, even in the absence of effects on body composition. The blood pressure‐lowering effects of Ang‐(1‐7) appear to involve a decrease in cardiac sympathetic tone; although further studies are needed to confirm these findings. These overall data suggest Ang‐(1‐7) may provide a novel pharmacological target to improve age‐related cardiovascular risk.

Support or Funding Information

NIH 5 R00 HL122507‐04, American Heart Association Postdoctoral Fellowship 18POST33960087

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelin B Receptors are Necessary for Appropriate Renal Afferent Nerve Responsiveness
Authors: Becker Bryan K , Kopp Ulla C , Pollock David M
Published: June 2021

Salt‐sensitive hypertension is a major health burden with end results of increased mortality and morbidity worldwide. Many factors contribute to salt‐sensitive hypertension including endothelin (ET) system dysfunction and aberrant sympathetic nerve activity. Previous work has highlighted the involvement of the ET system in modulating sympathetic tone; however, a complete understanding of the interactions involved remains elusive. Prior studies suggest that ETB receptors sensitize renal afferent nerves in response to high salt diet, which initiates a feedback loop via the renorenal reflex to inhibit efferent renal nerve activity and thus promote natriuresis. Rats lacking functional ETB receptors in all tissues except adrenergic tissues (ETB ‐def) are hypertensive, salt‐sensitive, and have elevated sympathetic tone. We have shown that bilateral renal denervation in ETB‐def rats attenuates blood pressure along with markers of global autonomic tone suggesting a role for afferent renal nerves in mediating hypertension in this model. Here, we hypothesized that ETB ‐def rats would have attenuated afferent nerve activation compared to transgenic (TG) controls. Renal pelvic walls were collected from TG and ETB ‐def rats and treated with prostaglandin E2 (PGE2). Substance P release was measured as an indicator of the activation of afferent nerves within the isolated pelvic walls. Substance P release was significantly higher in pelvic walls following treatment with PGE2 from TG compared to ETB ‐ def male rats (9.5 ± 2.8 vs. 0.1 ± 0.5 pg/min, p < 0.01, n = 5/group, respectively) and females (8.1 ± 1.2 vs. 0.7 ± 1.0 pg/min, p < 0.05, n = 5/group, respectively). Substance P release in response to capsaicin was not different between genotypes (4.2 ± 1.3 vs. 4.6 ± 1.8 pg/min, p = 0.85, n = 6/group, TG vs. ETB ‐def) indicating intact afferent nerve responsiveness. Preliminary data further indicate that ETB‐def animals do not display reduced renal sympathetic tone following a high salt diet. Rats were fed either a normal salt diet (0.49% NaCl) or high salt diet (4% NaCl) for 7–10 days, and total renal nerve activity was measured in anesthetized rats. TG controls tended to have lower nerve activity following high salt (1.8 ± 0.3 vs. 1.1 ± 0.2 mV.ms, n = 3–4/group, normal vs. high salt). Conversely, ETB‐def rats failed to display this reduction in sympathetic tone (1.8 ± 1.0 vs. 3.2 ± 0.3 mV.ms, n = 3/group, normal vs. high salt). These data indicate that salt‐sensitive ETB ‐def rats have impaired afferent renal nerve responsiveness, which results in a lack of renorenal reflex mediated sympathoinhibition.

Support or Funding Information

Supported by T32 HL007457 to BKB, and P01 HL069999 and P01 HL136267 to DMP.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of the Endothelin System in the Progression of Acute Kidney Injury to Chronic Kidney Disease
Authors: Czopek Alicja , Stewart Kevin , Moorhouse Rebecca , Bailey Matthew A , Dhaun Neeraj
Published: June 2021

Introduction

Acute kidney injury (AKI) is the most common cause of organ dysfunction in critically ill patients, increasing the risk of developing chronic kidney disease (CKD) by 30%. Endothelin‐1 (ET‐1) is the most potent endogenous vasoconstrictor mediating its effects through two receptors – the endothelin‐A receptor (ETA) and endothelin‐B receptor (ETB). The ET system is upregulated in AKI and CKD. We investigated the role of the ET system in the progression of AKI to CKD using the renal ischemia‐reperfusion injury (IRI) model.

Methods

Study 1

50 min of unilateral IRI was induced by occlusion of the left renal pedicle in male FVB mice. Starting 24h after injury, mice received either 4 weeks of sitaxentan (a selective ETA receptor antagonist; n=12) or vehicle (n=12) in drinking water. Blood pressure (BP) was recorded continuously over the 4‐week period via radiotelemetry and kidney fibrosis assessed at the end.

Study 2

Using a similar protocol, mice received either sitaxentan (n=8) or vehicle (n=8) for 5 days after which animals were anesthetized and BP measured using a carotid artery cannula, and renal cortical and medullary blood flows measured in the IRI kidney by laser Doppler flowmetry. We assessed systemic and renal hemodynamic responses to brief intravenous infusion of angiotensin II (ANG II).

Results

Study 1

Unilateral renal IRI led to a sustained increase in BP of ~8 mmHg and significant fibrosis within the IRI kidney. Sitaxentan completely prevented this BP rise and the development of fibrosis.

Study 2

In healthy mice, brief ANG II infusion increased systemic BP and reduced renal cortical and medullary blood flow. Unilateral renal IRI enhanced the BP rise seen with ANG II infusion and significantly attenuated the falls in renal cortical and medullary blood flow in the IRI kidney. 5 days of sitaxentan treatment improved the renal hemodynamic response to ANG II.

Conclusions

We have demonstrated that administration of a selective ETA receptor antagonist improves the perturbations in systemic and renal hemodynamic seen in a model of AKI transitioning to CKD. These may be of important therapeutic benefit and should be pursued in a clinical trial in relevant patient groups.

Support or Funding Information

This work was funded by the British Heart Foundation and the Medical Research Council.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chronic Intermittent Hypoxia is Associated with Sustained Reduction in Renal Blood Flow and Downregulation of Renal KLF2
Authors: Twohey Stephanie C. , Kious Kiefer W. , Keomanivong Faithe E. , Neidermann Sarah E. , Dirkman Jacob J. , Marcus Noah J.
Published: June 2021

Background and Rationale

Sleep apnea (SA) is associated with hypertension and chronic kidney disease. Dysregulation of blood pressure control and renal damage may occur because of the chronic intermittent hypoxia (CIH) that occurs during SA. Reductions in renal blood flow (RBF) during or after CIH may lead to renal injury by contributing to recurrent tissue hypoxia and alterations in shear‐stress (SS) related signaling. Krüppel‐like factor 2 (KLF2) is a SS‐sensitive transcription factor that controls expression of antioxidant and anti‐inflammatory gene programs.

Hypothesis

We hypothesized that CIH would result in baseline reductions in RBF and exacerbate subsequent reductions in RBF during hypoxia. Furthermore, renal KLF2 expression will be reduced along with attendant changes in its downstream targets.

Methods

Adult male Sprague Dawley rats were exposed to 10 days CIH (60 sec. 10% O2, 120 sec. 21% O2) for 8h/d. Post‐CIH (or sham) RBF was measured using Transonic flow probes before, during, and after exposure to 10% O2. After euthanasia, renal cortical and medullary tissue was probed for expression of KLF2, interleukin 6 (IL‐6), superoxide dismutase (SOD1), neutrophil gelatinase‐associated lipocalin (NGAL) via western blot.

Results

Baseline weight‐corrected RBF was lower in CIH vs. sham (1.89±0.13 mL/min/g vs. 1.42±0.16 mL/min/g, p<0.05), and the RBF response to 10% O2 was accentuated in CIH vs. sham (−45±14% CIH vs. −26±4% sham, p<0.05). During recovery, RBF at 20 min post‐hypoxia remained below baseline values in both groups (93±3% of baseline sham vs. 85±4% of baseline CIH, P>0.05). Ten consecutive episodes of 10% O2 elicited reductions in RBF that persisted after return to 21% oxygen and which were significantly reduced from baseline for the duration of the exposure period (p<0.05). Cortical and medullary KLF2 expression were decreased by 40–50% in CIH relative to sham (1.00±0.21 sham cortex vs. 0.46±0.08 CIH cortex, and 1.00±0.24 sham medulla vs. 0.44±0.10 CIH medulla, p<0.05 for both comparisons). Cortical SOD1 expression was reduced in CIH relative to sham (1.00±0.00 sham vs. 0.72±0.12 CIH, p<0.05), whereas IL‐6 expression was increased (1.00±0.19 sham vs. 1.56±0.21 CIH cortex, p<0.05). Medullary NGAL was increased in CIH vs. sham (p<0.05).

Conclusion

Persistent reductions in RBF during and after apneic episodes (CIH) may contribute to renal inflammation, oxidative stress, and injury via downregulation of KLF2.

Support or Funding Information

Supported by a grant from NHLBI (R15 HL138600‐01 to NJM)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Involvement of AKT/FOXO Genes in the Interactions of PPARα and PHD in DOCA‐Induced Pathology
Authors: CHOI MYUNG , OYEKAN ADEBAYO
Published: June 2021

Prolyl hydroxylase (PHD) and peroxisome proliferator activated receptor (PPAR)α, known “sensors” of cellular energy and/or oxygen and have been demonstrated to mitigate against oxidative stress, inflammation and fibrosis in cardiorenal pathologies. However, it is not fully known if any commonality exists in their mechanisms of action. This study evaluated the role of Akt/Forkhead box protein FOXO pathway as a possible common target for both PHD and PPARα. In uninephrectomized rats treated with DOCA and 1% NaCl, hypertension was accompanied by cardiac/renal hypertrophy (P<0.05) and marked proteinuria (P<0.01). Accompanying these effects were increases in the expression of TGFβ (72±14%), a marker of fibrosis, p65 (60±7%), an index of inflammation, pAkt (82±10%), a key signaling protein in cellular function, and PHD2 (90±8%), an index of hypoxia but reduced expression of FOXO1 (27±4%) and PPARα (27±6%). Clofibrate, a PPARα ligand, attenuated the hypertension (P<0.05), organ hypertrophy and proteinuria (P<0.05) and blunted the expression of PHD2 (45±6%, P<0.05), pAKt (66±4%, P<0.05), TGFb (P<0.05) and p65 (P<0.05) without changes in MnSOD expression. Combined administration of clofibrate and DMOG, the inhibitor of PHD, exacerbated these effects. These data suggest that FOXO proteins may compliment the activities of PPARα. Moreover, PPARα activation and PHD2 inhibition resulted in similar signaling mechanisms and that combined PPARα activation and PHD2 inhibition may constitute a more effective therapeutic approach in the management of hypertension.

Support or Funding Information

National Institutes of Health grant G12MD007605

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of Epac1 or Epac2 compromises renal Na+ conservation by decreasing activity of the epithelial Na+ channel (ENaC)
Authors: Tomilin Viktor N , Zaika Oleg , Mei Fang , Cheng Xiaodong , Pochynyuk Oleh
Published: June 2021

Exchange proteins directly activated by cAMP (Epac1 and Epac2), along with protein kinase A (PKA), are major downstream effectors of the universal intracellular second messenger cAMP, which serves as a nexus of multiple endocrine inputs to regulate renal tubule water and electrolyte transport. We previously demonstrated that deletion of either Epac isoform, namely Epac1 or Epac2, diminishes urinary concentrating ability by reducing fluid reabsorption in the proximal tubule. Here, we employed balance studies in combination with direct electrophysiological assessment of Na+ influx in distal tubule segments from mice with targeted deletion of Epac1 or Epac2 to investigate the role of Epac cascade in tuning urinary Na+ excretion during variations in dietary salt intake. 24 h urinary Na+ levels were comparable in Epac WT and Epac isoform knockouts when animals were subjected to a regular salt intake (0.32% Na+). In contrast, we detected a delayed anti‐natriuretic response during the first 2 days of dietary sodium restriction (<0.01% Na+), which was more pronounced in Epac2 “−/− mice. Consistently, patch clamp analysis in freshly isolated split‐opened collecting ducts found indistinguishable activity (NPo) of the epithelial Na+ channel (ENaC) between Epac WT and Epac2 −/− mice on a regular salt intake: 0.37±0.03 and 0.36±0.05, respectively. Low salt diet greatly increased ENaC activity in Epac WT to 0.75±0.05 as expected, whereas this response was significantly blunted in Epac2 −/− mice (NPo = 0.48 ± 0.06). This was associated with a decrease in both number of active channels per patch and ENaC open probability. In summary, our results support a role of Epac signaling cascade (with a higher contribution of Epac2) in stimulation of ENaC activity by dietary salt restriction. We further propose that reduced ENaC‐mediated Na+ reabsorption at least partially contributes to impaired renal salt conservation in mice with deleted Epac isoforms.

Support or Funding Information

National Institutes of Health (NIH)‐National Institute of Diabetes and Digestive and Kidney Diseases Grants DK119170 (to O.P.), AHA Grant 17GRNT33660488 (to O.P.), ASN Ben J. Lipps Research Fellowship (to V.T.)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of body composition and visceral adiposity index in breast cancer
Authors: Peña Elias Cardoso , de Jesús Garduño García Jose , Villanueva Ángel Gómez , Chávez Emilio López , Soto Piña Alexandra E.
Published: June 2021

Breast cancer and obesity are two diseases that currently occur in a high percentage of women population. Central obesity is an important risk factor for developing breast cancer. Both obesity and cancer are characterized by a chronic state of inflammation in part maintained by cytokines secreted by fat tissue; however, it is not clearly known how they are linked to each other. The aim of this study was to compare body composition and visceral adiposity index (VAI) between women with and without breast cancer. The participants included women 40–60 years old, with stages I and II of breast cancer, who voluntarily accepted to participate in the study. The control group comprised women with BIRADS 1, 2 and 3 mammograms, and the same age span. General sociodemographic data, hereditary family history of breast cancer, gyneco‐obstetric history and histopathological classification of breast cancer were recorded for each participant. Additionally, body composition was evaluated with electrical bioimpedance using an InBody230 equipment. In order to compute the VAI, concentrations of triacylglycerols and high‐density lipoproteins cholesterol (HDL‐c) were measured by colorimetric tests. Data were analyzed using Mann‐Whitney test. The results showed that women with breast cancer presented a higher mean of body mass index (BMI) than the control group (30.4 ± 3.8 Kg/m2 vs 26.5 ± 2.6 Kg/m2, respectively); but these were not significant different (p=.99). The VAI in women with breast cancer was 4.5 ± 0.8, but in the control group was 3.9 ± 0.5; however they were not significantly different. In summary, women with breast cancer showed a higher BMI and VAI, which suggests these markers of obesity might be useful in the diagnostics procedures for this type of cancer, but further analysis in a bigger population is required.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessment of the expression profile of circulatory adiponectin and biochemical parameters in broilers
Authors: Lin Yuan‐Yu
Published: June 2021

Novel studies have found that adipokines can serve as human clinical biomarker or regulate mammalian metabolic functions, but the researches of adipokines on the regulation of metabolic function of avian is still limited. The current study is to investigate the profile of plasma adiponectin and biochemical parameters in broilers, and expect to able to establish basic information and have the deeper possibilities for study metabolic function later.

One hundred and fifty Arbor Acres broilers were adapted from the Broiler Management Manual that divided growth into different growth stages. The data of body weight, plasma, and feed consumption were collected at day3, day 7, day 14, day 21, day 28 and day 35. Plasma was used to analyze adiponectin (ADP), macroadiponectin (MADP) and biochemical parameters, such as triglycerides (TG), total cholesterol (TCHO), glucose (GLU), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL). Results are showed that adiponectin have highly negative correlation with age and macroadiponectin have highly positive relevance with age on both gender in broilers. Moreover, body weight has highly negative correlation (r value, −0.746) with adiponectin and positive correlated with macroadiponectin.

This study is first comprehensive explore the profile of adiponectin and its correlation with biochemical values and physiological status in various growth stages which can provide the basis for metabolic study in avian species.

Support or Funding Information

Funds for this work were provided by Ministry of Science and Technology, Taiwan (project no. 106‐2313‐B‐029 ‐003 ‐MY2).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Sepsis on Circulating CTRP3 Levels
Authors: Musick Adam , Shipley Madison M , Tu Fei , Li Chuanfu , Yakubenko Valentin , Peterson Jonathan
Published: June 2021

Adipose tissue is an active endocrine organ which secrets several pro‐ and anti‐ inflammatory mediators, collectively called adipokines. Our previous work has identified a novel anti‐inflammatory adipokine called C1q TNF Related Protein 3 (CTRP3). Localized overexpression of CTRP3 protects myocardial tissue from lipopolysaccharide (LPS)‐induced sepsis, indicating a potential protective role of CTRP3. However, endogenous regulation of CTRP3 in response to a sepsis event has not been explored. Therefore, the purpose of this project was to explore the potential role of CTRP3 in sepsis by determining the effects of a sepsis event on circulating CTRP3 levels.

METHODS

Gonadal adipose tissue and serum were collected 8 hours after induction of the cecal‐puncture and ligation (CLP) model of sepsis or sham control mice. The circulating levels of CTRP3 were quantified by immunoblot analysis. The transcription levels of CTRP3 in adipose tissue were measured by Real‐Time PCR. In addition, to explore a potential mechanism for a protective role of CTRP3, thioglycollate‐induced peritoneal macrophages were isolated and binding of recombinant CTRP3 protein was determined by imaging flow cytometry.

RESULTS

CLP‐induced sepsis reduced circulating CTRP3 levels by ~90%, compared to sham treated mice. However, there was no difference in the CTRP3 mRNA level. Further, imaging flow cytometry demonstrated that CTRP3 binds directly to isolated macrophages.

CONCLUSION

The observed reduction in circulating CTRP3 protein levels combined with the absence of changes to the CTRP3 transcription level, indicate that during sepsis CTRP3 is actively removed from the blood. Combine these data support future research to determine if circulating CTRP3 levels are a biomarker indicative of sepsis prognosis. In addition, as CTRP3 binds to and inhibits macrophage activation future research should also determine if restoring circulating CTRP3 levels could reduce the cytokine storm associated with a sepsis event.

Support or Funding Information

NIH NIDDK R15DK105496

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of oral fat stimulation on fat taste perception and preference among Japanese young men and women
Authors: Yamauchi Yuho , Inoshita Mmiko , Ueshima Kyouko , Uchida Yuki , Takamata Akira , Morimoto Keiko
Published: June 2021

Recent evidence suggests that oral chemoreception is involved in the detection of fat via its breakdown products, fatty acids. In addition, long‐term consumption of high‐fat diet was reported to decrease oral fatty acid sensitivity. However, it is unclear whether dietary fat temporarily modulates fat taste perception and preference. We examined whether dietary fat stimulation of lingual lipid sensors affects oral fatty acid sensitivity and fat preference, and compared the results with those of sucrose among healthy young Japanese men and women. In addition, we assessed the sex difference or effects of sex hormones on the basal level of oral fatty acid sensitivity, fat preference, and changes in their levels after dietary fat stimulation.

Female subjects participated in laboratory experiments three times in a random order in the early and late follicular phases, and mid‐luteal phases during the menstrual cycle, and male subjects did so on an arbitrary day. To test oral fatty acid sensitivity, oleic acid (C18:1) detection thresholds were determined using a three‐alternative forced‐choice methodology. The fat preference test was carried out by choosing the preference for cottage cheese containing four different concentrations of food lipids. Measurements of oleic acid detection threshold and fat preference were repeated after a lingual stimulation by 5 min exposure of dietary fat or sucrose. After the experiments, subjects consumed a buffet‐style lunch where they ate various food items until comfortably full, and their energy intake, fat intake, and fat‐energy ratio was assessed. We analyzed the relationship between oleic acid sensitivity and fat preference, or energy intake and the effects of sex hormones on these variables.

Oral oleic acid thresholds did not vary between men and women in the early follicular phase, but changed in three phases during the menstrual cycle in women. Short‐term lingual stimulation with dietary fat enhanced the oleic acid thresholds in both women and men. In addition, there was a correlation between the oleic acid threshold and energy intake after the stimulation. The present result suggests that oral fatty acid sensitivity decreases after dietary fat stimulation and mediates total energy intake in a meal. Additionally, ovarian hormones possibly affect energy intake through oral fatty acid sensitivity in women.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Experimental Pediatric Obesity Impairs Central Control of Food Behavior
Authors: da Silva Aline Isabel , Braz Glauber Ruda F , Silva Severina Cassia A , Silva Tercya Lucidi A , Lagranha Claudia
Published: June 2021

According to WHO in 2016, 41 million children in their frist5 years of age are either overweight or obese. Overweight and obese children have a higher risk to stay obese into adulthood and present more incidences to develop chronic diseases. The control of the food and energy intake is essentially controlled and integrated by hypothalamic neuropeptide with anorexigenic and orexigenic functions such as ‘cocaine‐and‐amphetamine‐regulated transcript (CART) co‐expressing neurons, which suppress feeding behavior or activation of agouti related‐peptide (AgRP) co‐expressing neurons that induces an increase in appetite response. Additionally to the peptides, specific receptors also play a key role in the control of the food behavior, such as 5‐HT1b and 5‐HT2c, acting regulating meal size and eating rate in association to the neuropeptides. Until the moment the effect of pediatric obesity and the expression of these neuropeptides and receptors remains to be more explored. Three days after delivery, the puppies were randomly assigned into two groups: Controls (nine pups per mother, n=6) or Overfed (three pups per mother, n=6). At 21 days, all male pups began to receive water and commercial chow ad libitum until 60 days of age. We evaluate body weight‐BW, 24 hours food intake‐FI, blood glucose and triglycerides levels, CART, AgRP, 5‐HT1b, and 5‐HT2c gene expression. Our data demonstrate that reduction in litter size induce the increase in BW since the seventh day of life and maintains until the sacrifice (7, 22, 60th, p<0.001). Associated with BW, we observed an increase in FI in dark cycle (p<0.01) and in light cycle (p<0.05). Evaluating serum patterns, we verify an increase in glucose (p<0.05) and in triglycerides (p<0.001). At the molecular levels, we observe an impressive decrease in CART expression (p<0.001) in the overfed group. Taken our data together, we suggest that neonatal overfed induce energetic disturb increasing the risk of metabolic syndrome in a possible mechanism mediated to alteration on neuropeptide signaling in the central control of food behavior.

Support or Funding Information

FACEPE APQ grant #0164‐4.05/15; This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES) ‐ Finance code 001

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sweeteners as a Cause of Alteration in the Consumption of Food, Water, Variation in Percentage of Lymphocytes and Cytokines
Authors: DE MARIA CRUZ ESTRADA FLOR , CARRILLO BEATRIZ ELINA MARTINEZ
Published: June 2021

BACKGROUND

The use of sweeteners influences the appetite, activation of immune responses and release of proinflammatory factors, causing increased glucose and weight, generating acute inflammation.

OBJECTIVE

To evaluate the effect of sweeteners as a cause of alterations in the consumption of food, water, variation in the percentages of lymphocytes and cytokines.

MATERIAL AND METHOD

A total of 96 male mice CD1 [Crl: CD1 (ICR)] with eight week old, divided into three groups: CD1 (A), CD1 (B) and CD1 (C); each group with n = 32 subdivided into a control group: with a normal standard diet (rodent laboratory chow 5001 purine [3.02kcal/gr] and water ad libitum; one supplemented with sucrose (41.66 mg/mL), with stevia (4.16) mg/mL) and sucralose (4.16 mg/mL) respectively The weight, feed intake and water, percentage of B lymphocytes and cytokines (IL‐6, TNF‐a and INF‐g) were calculated initially, intermediate and final in each group.

RESULTS

Mice with sucrose from the CD1 (A) group consume less food, more water and have high glucose levels. There is weight gain in the three CD1 (B) groups supplemented; mice with sucrose and sucralose consume more food; lymphocytes elevated in peyer's plates by sucrose and decreased in spleen and blood by stevia and sucralose. High levels of TNF‐a by sucrose and high initial levels of INF‐g by the three sweeteners; low levels at the end in CD1 (C).

CONCLUSIONS

Sweeteners can influence as anorexigenic, however, they generate weight gain, elevation of glucose levels and acute inflammatory response.

Support or Funding Information

AUTONOMOUS UNIVERSITY OF STATE OF MEXICO

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This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does a High‐Fat Diet Mimic Biological Aging in Mice? A Preliminary Study
Authors: Ives Stephen , Bloom Samuel , Tuluca Andrei , Reynolds T.H.
Published: June 2021

Age and obesity are risk factors for many chronic diseases, which are linked to inflammation and oxidative stress, and is thought to alter telomere function. Telomeres are the endcaps of eukaryotic chromosomes that maintain chromosomal structural integrity protecting genetic information. Telomeres are regulated and protected by the shelterin complex, made up of Telomere‐repeat binding factor 1 (TRF1) and 2 (TRF2), protection of telomeres 1 (POT1a and b) as well as the enzyme telomerase that can elongate telomeres. However, to date, the effect of a high‐fat diet and age on the shelterin complex of telomeres in adipose tissue has not been examined. Thus, the present study investigated the effects of a high‐fat diet and aging on C57Bl6J (N=15) mice adipose tissue mRNA expression of genes involved in the regulation of telomeres. Young mice were randomly assigned to be fed either a high‐fat (YG+HF; n=5; 60% kcal from fat) or a low fat diet (YG+LF; n=4; 10% kcal from fat) for three months. A subset of mice were fed a low fat diet (AGED; n=6; 10% kcal from fat) and aged until 16 months.

RESULTS

Body weight and epididymal white adipose tissue weight (EWAT) increased with age or a high‐fat diet. TRF1 mRNA expression was reduced by age and a high‐fat diet, whereas age alone reduced TRF2. mTERT, the gene that codes for the catalytic subunit of the enzyme telomerase, was significantly higher in the YG+HF than the YG+LF and AGED mice (p=0.001). Body weight was significantly correlated with TRF1 and TRF2 mRNA expression (p=0.01), whereas mTERT expression was significantly correlated to EWAT weight (p=0.008). There were no significant differences between groups for mRNA expression of POT1A (p=0.928) and POT1B (p=0.930), respectively. To understand potential impacts of alterations to shelterin complex proteins on phenotype we probed for tumor necrosis factor α (TNFα) and monocyte chemoattractant protein 1 (MCP1), though unexpectedly, mRNA expression in adipose tissue were significantly elevated in the YG+LF group compared to the YG+HF and aged groups for TNFα (p=0.001) and MCP1 (p=0.000), respectively. We also assessed gene expression of the tumor suppressor protein p53, which is involved in the DNA damage response. There was no significant difference between groups for p53 mRNA expression (p=0.199). A high‐fat diet, increased the expression of mTERT, the catalytic subunit of the enzyme telomerase, but decreased TRF1, whereas age decreased mTERT, TRF1, and TRF2. POT1a, POT1b, p53 were not different. Together, these findings suggest diet and age impact expression of the shelterin complex, and perhaps telomere function in adipose tissue which might be associated with the development of chronic disease associated with obesity or aging, but further work is needed.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High plasma soluble prorenin receptor (sPRR) levels correlate with systolic blood pressure in aged male but not in female mice
Authors: Visniauskas Bruna , Wong Christopher TU , Crabtree Stephanie L , Hong Jennifer , Reverte Virginia , Rosales Carla B , Mejia‐Gomez Hernan , Mostany Ricardo , Prieto Minolfa C
Published: June 2021

Elderly subjects are predisposed to intrarenal renin‐angiotensin system (RAS) activation, which increases the risk for hypertension, kidney injury, and chronic kidney disease (CKD). The prorenin receptor (PRR), a component of the RAS that enhances the activity of renin and fully activates prorenin, is upregulated in the kidney in hypertensive rodent models. PRR possesses two molecular forms, a cell membrane bound and a soluble form (sPRR). Levels of sPRR in plasma are elevated in patients with cardiovascular diseases, including hypertension, preeclampsia, diabetes, and CKD. In the present study we tested the hypothesis that age increases plasma sPRR, blood pressure, and renal function in mice. We used male and female C57Bl/J6 mice distributed in 4 groups according with age (months, m) and sex (♂/♀) as follows: 1) 4–6 m, N=8/5; 2) 8–10 m, N=8/7; 3) 15–19 m, N=12/7; and 4) +20 m, N=9/7. Systolic blood pressures (SBP, mm Hg) measured by the tail cuff method were increased in male mice in 15–19 m (118±1.9) and +20 m (129±2.9) groups, compared to 4–6 m (103.0±1.8) and 8–10 m (105.0±1.6); p<.0001). No significant changes in SBP were observed in females. SBP positively correlated with age in male mice only (r=0.669; p=0.001). Plasma sPRR levels measured by ELISA (IBL America, Inc) did not differ between male and female young mice (10 m or younger). However, plasma sPRR levels were significantly higher in male mice of 15–19 m (3.8±0.2 ng/ml) and even greater in older mice (+20 m: 4.9±0.4 ng/ml), compared to 4–6 m (1.8±0.2 ng/ml) and 8–10 m (1.8±0.1 ng/ml) (p<.001). In contrast, only female mice older than 20 m of age showed significant increased plasma sPRR (4.3±0.1 ng/ml) compared to younger mice (p=0.03). Interestingly, plasma sPRR was positively correlated with SBP (r=0.602, p=0.02) in males but not in females. No differences were found in plasma and urine creatinine, osmolality, and BUN, or in urinary sodium concentration and proteinuria among groups. We conclude that: 1) Age positively correlates with SBP in male mice but not in females; 2) Plasma sPRR levels increase with age in male and female mice; and 3) Plasma sPRR levels are associated with SBP in aged males but not in female mice. The data suggests that age‐associated increases in plasma levels of sPRR and SBP are more sensitive to advanced age in male than in female C57Bl/6J mice. Further studies are needed to define whether hormone effects on plasma sPRR and SBP are independent or not of age.

Support or Funding Information

Support from NIH‐NIDDK (R01DK104375) to MCP; NIH‐NIA (R01AG047296) to RM

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Efficacy of Intermittent Fasting in Weight Reduction in Non‐obese and Obese Rats
Authors: Niepoetter Paige , Colley Zachary , Viernow Coral , Allen Alyssa , Gopalan Chaya
Published: June 2021

Obesity is a major contributing factor in the development of many chronic conditions such as type 2 diabetes and hypertension. Intermittent fasting (IF) isa pattern of feeding that cycles between periods of fasting and eating. It allows eating within a specific time period, and fast during the rest of the day. Intermittent fasting appears to be a promising approach to prevent or reverse obesity. Our project involved the induction of obesity using a high fat diet (HFD; D12492‐60% kcal diet) in male Sprague Dawley rats. Blood glucose and ketone levels were measured twice a week and daily body weights were monitored. The rats being fed on the HFD gained 12% more weight than those on a standard diet (SD) and 14% weight gain compared to the growth chart of the animal supplier within seven weeks of feeding this special diet. Blood ketone and glucose levels remained unchanged between these groups. The animals with HFD, now referred to as the obese (OB) group and those with SD referred to as non‐obese (non‐OB) rats were placed on IF next. Intermittent fastingin this experiment was designed to allow animals to eat for 6 hours during their nocturnal window of time and fast during the remaining 18 hours. The OB and non‐OB groups were subdivided into five groups during the IF study: (1) OB rats on IF who were given HFD (OB‐IF‐HFD; N=3), (2) OB rats on IF given SD (OB‐IF‐SD; N=3), (3) OB rats maintained on HFD ad libitum (OB‐non‐IF; N=4), (4) non‐OB rats on IF with SD (non‐OB‐IF; N=3), and (5) non‐OB rats maintained on SD ad libitum (non‐OB‐non‐IF; N=3). Within three weeks of exposure to IF, there was a significant (p<0.05) decrease in body weight in the IF groups compared to the non‐IF groups receiving food ad libitum. However, blood ketone levels were significantly increased in the non‐OB‐IF rats compared to non‐OB‐non‐IF group, blood glucose levels were significantly decreased. A significant decrease in blood glucose levels was also noted in the OB‐IF‐SD group compared to OB‐non‐IF animals. This study suggests that HFD induces obesity as measured by body weight in approximately seven weeks, which can be reversed by subsequent practice of IF for three weeks but depends on the nature of the diet being used during IF i.e., IF‐induced weight loss with HFD is significantly less than with SD.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chloroquine, an Activator of Bitter Taste Receptors, Relaxed Male Guinea Pig Gallbladder Strips
Authors: Kline Loren
Published: June 2021

Taste receptor cells are present in several extra‐oral locations such as the gut, human airway smooth muscle, vascular smooth muscle, and myometrial smooth muscle. A pharmacologic approach was used. The purpose of this study was to determine if the motility of the gallbladder was affected by a bitter tastant such as chloroquine (ChQ). ChQ relaxed both cholecystokinin octapeptide (CCK)‐ and KCl‐induced tension in a concentration dependent manner. There was no significant difference in the amount of ChQ‐induced relaxation of either CCK (1.0 nM) ‐ or KCl (40 mM)‐induced tension at any concentration of ChQ used (50, 100, 150, and 200 mM). In some strips ChQ induced a transient tension (0.4 g lasting 1.4min). To determine if ChQ inhibited extracellular Ca2+ entry, ChQ was added to the chambers prior to the CCK a significant decrease in the amount of CCK‐induced tension was observed (1.12±0.08 vs. 0.9±0.06 g, n=4, p<0.001). A similar result was observed when KCl was used (1.12±0.1 vs. 0.7±0.1 g, n=4, p<0.001). Penitrem A, a blocker of high conductance Ca2+ activated K+ channels, decreased the amount of ChQ‐induced relaxation (34.5±4.3 vs. 27.0±3.2%, n=3, p<0.02). Bisindolylmaleimide IV (BIM) and chelerythrine Cl− were used together to block PKC. They significantly decreased the amount of ChQ‐induced relaxation (23.8±3.2 vs. 18.9±3.0%, n=3, p<0.03). Neither PKA‐IM, a PKA blocker, nor KT5823, a PKG blocker, had a significant effect on the amount of ChQ‐induced relaxation. ChQ relaxed guinea pig gallbladder strips by blocking extracellular Ca2+ entry and blocked the actions of PKC.

Support or Funding Information

This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.