bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent hypoxic exposure and exercise training positively affect body composition and energy substrate utilization in high-fat diet-induced obese mice
Authors: Jang Inkwon , Park Yeram , Kyun Sunghwan , Hwang Deunsol , Yoo Choongsung , Park Hun-Young , Kim Jisu , Lim Kiwon 
Published: May 2023

Obesity is considered a major risk factor for increasing insulin resistance and inducing type 2 diabetes. Exercise is known to be the most effective treatment for improving obesity and insulin resistance through body fat loss. Furthermore, hypoxic exposure is known to increase carbohydrate oxidation and improve overall energy expenditure. Therefore, in this study, the effect of combined treatment of exercise and intermittent hypoxia on body composition and metabolic improvement was investigated after inducing obesity through a high-fat diet.The male 5-week-old ICR mice consumed high-fat diet for 7 weeks and were fed ad libitum. After 7 weeks, all groups were randomly divided into 4 groups: CN (sedentary; non-trained), HP (hypoxic exposure; non-trained), EX (trained), and HE (hypoxic exposure and trained). The HP and HE were only exposed hypoxia condition (12% oxygen concentration) for during light phase to coincide with the mouse inactive cycle. The EX and HE conducted treadmill training with 5 times a week for 4 weeks, and the exercise intensity was 70 % of VO2 max. After 4 weeks, the resting metabolic rate (RMR) was measured for all groups through respiratory gas. Then, all mice conducted dual energy X-ray absorptiometry to determine body composition.In body composition results, long-term exercise treatment showed a significantly decrease in fat mass and a significant increase in lean mass. In addition, in the HE, had significantly lower body fat mass and significantly higher lean mass than the EX. Furthermore, in the RMR results, it was investigated that overall energy expenditure increased through an increase in VO2 and VCO2 in the exercise group. However, in the HE, it was confirmed that carbohydrate oxidation at rest was significantly higher than that of the EX. In addition, it was confirmed that fasting blood glucose and HOMA-IR, an indicator of insulin resistance, were also significantly improved in the HE than in the EX.In summary, these results demonstrated that long-term exercise training decrease fat mass and increase in lean mass in high-fat diet-induced obese mice. In addition, it was confirmed that the HE, which intermittent hypoxic exposure combined treatment with exercise, significantly improved body composition compared to the EX, as well as improved carbohydrate oxidation at rest, fasting blood glucose, and HOMA-IR. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
B1-adrenergic blockers preserve motor function by inhibiting the production of extracellular traps
Authors: Bourcier Camille , Michel-Flutot Pauline , Emam Laila , Adam Lucille , Gasser Adeline , Vinit Stephane , Mansart Arnaud 
Published: May 2023

Sepsis is characterized by a dysregulated host response to an infection, potentially leading to fatal organ dysfunctions. Among these organs, the central nervous system (CNS) is particularly affected with encephalopathies associated or not with chronic disabling pain. These symptoms are caused by broad neuroinflammation with activation of resident microglia cells and infiltration of leukocytes, especially neutrophils. These immune cells have the ability to produce extracellular traps (ETs) in blood and tissues. These components are composed of chromatins and various antimicrobial proteins, and its role is to capture and destroy pathogens. However, in case of excessive production, deleterious effects occur such as tissue damage and reduction of neuronal excitability.In this study, the objectives were: 1) to determine whether in a model of endotoxemic shock, neutrophils and microglia form ETs in the CNS; 2) and to determine if a modulation of ETs production was beneficial on neuromuscular disorders associated with endotoxemic shock.We observed an infiltration of neutrophils in the SNC, an activation of microglia and a production of ETs following intraperitoneal lipopolyssacharide (LPS) administration in mice (adult Swiss male, 30-45g). Atenolol, a β1-adrenergic blocker with intrinsic immunomodulatory properties, significantly decreases the production of ETs associated in both microglia and neutrophils (citrullinated histone H3: 279.1 ± 101.9 MFI versus 117.1 ± 77.21 MFI, p<0,01). In addition, this treatment preserved the gastrocnemius motoneurons excitability (39,93 ± 15,16 mV in control group, 8.147 ± 5.892 mV in LPS group and 27.32 ± 10.73 mV in LPS+atenolol group). Similar results have been observed when the production of ETs was prevented by using sivelestat (inhibitor of extracellular traps).In conclusion, our results demonstrate that sepsis increases neutrophil infiltration into the spinal cord, activates immune cells and produces extracellular traps that directly impair motor function. Prevention of ETs formation partly restores motor function and could be a good target in order to reduce adverse effects in sepsis but also in other motor related pathologies. This work was supported by funding from the Chancellerie des Universites de Paris (Legs Poix), INSERM and Paris-Saclay University-UVSQ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Plasma Insulin level have linkage with neurodegeneration in patients with type 2 DM
Authors: Shamansurova Zulaykho , Saatov Talat , Srivastava Ashok , Alimov Timur , Ibragimova Elvira , Ibragimov Zafar , Maksutova Nigora , Aikhodjaeva Mokhira , Ishankhodjaev Tokhir , Mustafakulov Mukhammadjon 
Published: May 2023

Introduction: Type 2 Diabetes Mellitus (DM2) viewed as a major cause for neurodegenerative and cognitive abnormalities. One of the possible reason for that should be insulin resistance and hyperinsulinemia two main clinical future of DM2. The mechanism relationship between insulin and development of diabetic neuropathy and encephalopathy not clear yet. Material and methods: In 51 DM2 patients in age between 42 and 64 years old, without neurologic complications or with presence of different stages of neuropathy/encephalopathy were observed clinically and diagnosis confirmed by neurologist. Patients divided into two groups according to presence of mild and severe neuropathy or encephalopathy. For lab study cubital venous blood plasma taken for measure of plasma insulin level by ELISA. Results: Neuropathy/encephalopathy were registered in 71% of DM2 patients. HbA1c level were higher than healthy subjects and were comparable in both groups with severe neuropathy/encephalopathy and without. Blood plasma insulin level were between 14 and 21,7 μU/ml, significantly higher than normal ranges (0,7 – 9,07 μU/ml). Plasma insulin level were decreased according to severity of neuropathy/encephalopathy, and suggested about linkage between functional activity of beta-cells and neurodegeneration. Index HOMA-B indicates decreasing of beta-cells functional activity. Index Caro (glucose to insulin ratio) also been decreased and suggested about insulin resistance in these patients. When we analysed blood plasma insulin level according to presence and severity of diabetic neuropathy and encephalopathy there was significant Conclusion: Neurodegeneration is a frequent future of DM2 and were found in 71% cases. Presence and severity of neurodegeneration in DM2 have negative linkage with plasma insulin level and suggest about involvement of insulin resistance into pathogenesis of neurodegeneration. no funding or grants This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Signal transduction pathways of muscarinic receptors in the murine urinary bladder smooth muscle
Authors: Balla Helga , Borsodi Kinga , Örsy Petra , Horváth Béla , Molnár Péter József , Ruisanchez Éva , Nyirády Péter , Wess Jürgen , Offermanns Stefan , Benyó Zoltán 
Published: May 2023

Overactive bladder (OAB) is a clinical condition characterized by symptoms of frequency, urgency with/without incontinence. Despite of the fact that OAB affects millions of patients’ quality of life significantly, its etiology is still poorly understood. Currently, antimuscarinics are the first-line medical therapy for the management of OAB. However, their application is limited due to the decrease of patients’ compliance because of several adverse effects (e.g. dry mouth, obstipation).Our aim was to further analyze the signaling pathways of muscarinic receptors in detrusor muscle contraction with the goal of better understanding the intracellular regulation of micturition and identifying potential novel therapeutic targets for OAB.Experiments were performed on adult, male, wild-type (WT), M2, M3, M2/M3, Gαq/11 knockout (KO) and pertussis toxin (PTX)-treated mice. Contraction force and RhoA activity were measured in the urinary bladder smooth muscle (UBSM).Contractile responses induced by the muscarinic receptor agonist carbamoylcholine (CCh) in UBSM associated with increased activity of RhoA and were reduced in the presence of the Rho-associated kinase (ROCK) inhibitor Y-27632. The CCh-induced contractions were markedly reduced in detrusor strips lacking either M2 or M3 receptors and were abolished in UBSM from M2/M3 KO mice. The RhoA activation was decreased in both M2 KO and M3 KO bladders and it was completely reduced in M2/M3 KO UBSM. Inhibition of Gαi-coupled signaling by PTX-treatment shifted the concentration-response curve of CCh to the right and diminished RhoA activation. CCh-induced contractile responses were markedly decreased in Gαq/11 KO mice, however, RhoA activation was unaffected.In conclusion, cholinergic detrusor contraction and RhoA activation are mediated by both M2 and M3 receptors. Furthermore, CCh-induced contractions involve simultaneously the classical Gαq/11- and the Gαi-coupled signaling pathways, but the RhoA activation appears to be mediated exclusively by the Gαi proteins. These findings may aid the identification of more specific therapeutic targets for OAB. Hungarian NRDIO K-125174, K-135683, K-139230 and PD-132851, Ministry for Innovation and Technology from the Hungarian NRDI fund (2020-1.1.6-JÖVÖ-2021-00010, TKP2021-EGA-25), STIA-KFI-2021, EFOP-3.6.3-VEKOP-16-2017-00009 grants and Gedeon Richter Plc Talent Foundation This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
High salt intake during pregnancy and reno-cardiovascular disease in the offspring of C57Bl/6J mice
Authors: Ehmke Heimo , Seniuk Anika , Wageringel Isabel 
Published: May 2023

Background: In 1989, Barker et al. reported that a low birth weight is associated with a higher incidence of death from cardiovascular disease later in life. While this seminal observation resulted in a surge of experimental and clinical research, the precise mechanisms underlying this association remain incompletely understood. A reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells by midgestational stress have been shown to cause fetal growth restriction, suggesting that immunological mechanisms may contribute to fetal programming of cardiovascular disease. Recent findings ascribe immunological processes a decisive role in the pathogenesis of arterial hypertension. There is strong evidence that both, the innate and the adaptive immune system contribute to full development of hypertensive blood pressure levels and consecutive end-organ damage. Salt intake is a major modulator of the immune system. An increased salt intake promotes the induction of pathogenic murine and human TH17 cells, predisposing to the development of salt-dependent hypertension. Intriguingly, a low birth weight is also associated with a high incidence of chronic kidney disease in adulthood, a major risk factor for cardiovascular disease. Hypothesis: A high salt intake during pregnancy induces fetal programming of cardiovascular and renal disease by an alteration of the feto-maternal immune crosstalk. Methods and Results: Pregnant C57Bl/6J mice were exposed to a high salt diet starting at conception until weaning of the offspring. Aged offspring (>1 year) was then exposed to a second cardiovascular hit (high salt intake without and with additional angiotensin II infusion). Quantitative immune cell analysis, telemetric blood pressure measurement, determination of renal function as well as histopathological analysis did not reveal any significant differences between offspring from normal salt fed dams and high salt fed dams. Conclusions: Our results do not support a major role of perinatal high salt intake on fetal programming or the risk for development of cardiovascular and renal disease in later life. The study was financed by institutional budget. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effects of white adipose tissue denervation on baroreflex and inflammation markers in an experimental model of overweight
Authors: Nishi Erika , Milanez Maycon , Veiga Amanda , Campos Ruy , Bergamaschi Cassia 
Published: May 2023

Several neurohumoral factors contribute to cardiovascular dysfunction in obesity. In this study, we tested the influence of retroperitoneal white adipose tissue (rWAT) innervation on baroreflex control of blood pressure, inflammation in target organs and renal function markers in an experimental model of overweight in rats with increased sympathetic drive. Wistar rats were treated with high-fat diet (HFD) for 8 weeks and underwent surgical rWAT denervation (DNX) at 6 weeks (n=6/group). At the end of the experimental protocol, we found that DNX improved reflex bradycardia (HFD: -1.76 ± 0.19, HFD+DNX: -2.76 ± 0.20, Control: -2.36 ± 0.12 bpm/mmHg) and decreased hepatic and splenic proinflammatory cytokines in the HFD group. Moreover, serum angiotensinogen (HFD: 112 ± 10 vs HFD+DNX: 84 ± 12 uM) and leptin (HFD: 9.8 ± 1.2 vs HFD+DNX: 5.2 ± 0.8 ng/dL) were decreased after DNX. No change was found in renal cytokines or function markers. Therefore, these findings suggest that neural signaling from the rWAT contributes to cardiovascular changes and inflammation in target organs in rats treated with HFD. CAPES, CNPq and FAPESP This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Vitamin D mediated mitigation of fibrotic remodeling in asthma is associated with metabolic reprogramming
Authors: Ramakrishnan Rakhee , Kalaji Zaina , Bajbouj Khuloud , Halwani Rabih , Hamid Qutayba 
Published: May 2023

Vitamin D mediated mitigation of fibrotic remodeling in asthma is associated with metabolic reprogramming Rakhee K. Ramakrishnan1, Zaina Kalaji1, Khuloud Bajbouj1, Rabih Halwani1,2, Qutayba Hamid1,3 1 Sharjah Institute for Medical Research – College of Medicine, University of Sharjah, Sharjah, United Arab Emirates 2 Immunology Research Lab, College of Medicine, King Saud University, Riyadh, Saudi Arabia 3 Meakins-Christie Laboratories, McGill University, Montreal, Quebec, CanadaAsthma is a heterogeneous disorder that is associated with chronic airway inflammation and remodeling of the airways. While vitamin D deficiency has shown correlations with various clinical features of asthma, the mechanisms responsible for this action is poorly understood. This study therefore explored the molecular mechanisms associated with the anti-remodeling potential of vitamin D. We hypothesized that vitamin D induced metabolic reprogramming contributes to its anti-fibrotic activity. To this end, primary lung fibroblasts from asthmatic and non-asthmatic individuals were stimulated with TGF-β1 alone or in combination with the biologically active form of vitamin D, calcitriol. The expression of various fibrotic and metabolic markers was assessed both at the transcript and protein level. While vitamin D receptor (VDR) was constitutively expressed in human lung fibroblasts, calcitriol treatment induced a robust VDR response in asthmatic fibroblasts indicating increased VDR functionality in these cells when compared to normal. TGF-β1 stimulation led to an increase in the expression of several fibrotic markers, including COL1A1, COL3A1, COL5A1, FN1 and ACTA2, which was reversed after calcitriol treatment. These anti-fibrotic effects of calcitriol were associated with dysregulated AMPK signaling and an inhibition of TGF-β1-induced mitochondrial ROS release. Our findings thus, highlight the ability of vitamin D in regulating the cellular mitochondrial metabolism induced by TGF-β1 in lung fibroblasts, suggesting a possible mechanism associated with its anti-fibrotic activity. Since current asthma therapeutics do not effectively target the airway structural changes that are increasingly associated with asthma severity, vitamin D supplementation presents an attractive therapeutic avenue to attenuate subepithelial fibrosis and airway remodeling in asthmatic airways. We would like to acknowledge the funding received from University of Sharjah targeted research grant (ID 2101090295) in conducting this study. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Selective alpha 1-adrenergic blockade attenuates resting beat-to-beat blood pressure variability in healthy young men
Authors: Vianna Lauro , Rodrigues Gustavo , Daher Mauricio , Teixeira Andre , Fernandes Igor 
Published: May 2023

Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain incompletely understood. For instance, alterations in beat-to-beat blood pressure variability are thought to be driven by changes in both the reflex control of the autonomic nervous system and peripheral vascular function. To determine the role of peripheral sympathetic vasoconstriction on the beat-to-beat blood pressure variability, beat-to-beat heart rate (HR, by electrocardiography) and blood pressure (finger photoplethysmography) were continuously measured in seven healthy men (22 ± 5 yr) at rest (supine position), with and without (Control) a systemic and selective blockade of alpha 1-adrenergic receptors through the oral administration of Prazosin (1 mg/20 kg of body weight). Stroke volume was estimated from the blood pressure waveform (ModelFlow), permitting the calculation of cardiac output and total peripheral resistance. Two hours post-Prazosin ingestion, blood pressure responses to intravenous bolus infusion of phenylephrine were robustly reduced (-80 ± 15%, P = 0.001), indicating a significant functional blockade of alpha 1-adrenergic receptors. However, all resting hemodynamic variables were unchanged after the oral ingestion of Prazosin. Compared with control, Prazosin significantly reduced the standard deviation of systolic (5.5 ± 0.9 vs. 3.7 ± 0.7 mmHg, P = 0.004), diastolic (3.3 ± 1.0 vs. 2.4 ± 0.6 mmHg, P = 0.05), and mean blood pressure (3.7 ± 0.8 vs. 2.5 ± 0.5 mmHg, P = 0.02), as well as cardiac output (652 ± 251 vs. 428 ± 78 mL/min, P = 0.02) and total peripheral resistance (1.1 ± 0.6 vs. 0.5 ± 0.4 mmHg/L/min, P = 0.03). Similar results were found using different indices of blood pressure variability. Altogether, these findings suggest that peripheral sympathetic vasoconstriction plays a pivotal role in modulating resting beat-to-beat blood pressure variability in healthy young men. National Council for Scientific and Technological Development (CNPq; grant: 307293/2019-0 and 431740/2018-6). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Glucagon activates NCC in a glucagon receptor-dependent manner
Authors: Poulsen Søren , Baungaard Sara , Bourqui Laurent , Murali Sathish , Nørregaard Rikke , Loffing Johannes , Fenton Robert 
Published: May 2023

Introduction: Glucagon is raised during hypoglycemia in order to bring blood glucose back to normal levels. However, glucagon is paradoxically also raised under pathophysiological conditions where plasma glucose is high such as in diabetes mellitus (DM). DM is associated with hypertension, which contributes to diabetic kidney disease and other co-morbidities. The NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT) contributes to blood pressure control and the DCT also expresses the glucagon receptor. Therefore, we hypothesized that glucagon directly stimulates NCC via the glucagon receptor, and this may be a novel mechanism to modulate blood pressure. Methods: In vivo effects on NCC were studied in mice injected with glucagon. Ex vivo kidney tubules isolated from mouse and human kidney (obtained from tumor nephrectomized patients) were cultured and exposed to varying doses of glucagon alone, or in the presence of various inhibitors. The phosphorylation status of NCC was used as a surrogate marker for activity (increased phosphorylation = increased activity). Results: In kidneys isolated from mice 30 min after being injected with glucagon, NCC phosphorylation was increased. In ex vivo mouse kidney tubules, glucagon (1 nM to 1000 nM) exposure for 30 min increased NCC phosphorylation in a dose-dependent manner. 10 nM glucagon increased NCC phosphorylation after 5 min, an effect lasting up to 4 h. The glucagon receptor inhibitor 168,049 completely blocked the effect of 10 nM glucagon on NCC phosphorylation. The With No Lysine kinase (WNK) inhibitor StockS2, the inward-rectifier potassium channel 4.1/5.1 (Kir 4.1/5.1) inhibitor VU0134992, and the non-specific protein kinase A (PKA) inhibitor, H89, greatly reduced the effect of 10 nM glucagon on NCC phosphorylation. NCC phosphorylation was also increased in ex vivo human kidney slices exposed to 100 nM glucagon. Conclusion: We show for the first time that glucagon increases NCC phosphorylation in the mouse kidney both in vivo and ex vivo. The effect occurs via the glucagon receptor and involves WNK kinases, Kir4.1/5.1 and PKA. Glucagon effects can be observed ex vivo in human kidney slices, supporting that the findings may be relevant in humans. Whether glucagon-induced NCC phosphorylation contributes to the etiology of pathophysiological conditions manifested with raised plasma glucagon levels, such as DM, remains to be investigated. Novo Nordisk Foundation (NNF21OC0067647) and the Leducq Foundation (17CVD05). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.