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Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits? 空腹状态下过度换气对反复憋气的影响:风险是否大于收益?
IF 2.8 3区 医学 Q1 Medicine Pub Date : 2024-02-05 DOI: 10.1152/ajpregu.00260.2023
Antonis Elia, Mikael Gennser, Ola Eiken, Michail E. Keramidas
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print.
美国生理学杂志-调节、综合和比较生理学》,提前出版。
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引用次数: 0
Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling. 雄性Ts65Dn小鼠衰老后的心脏功能保留,但大小和烟酰胺腺嘌呤二核苷酸信号通路发生改变。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00164.2023
Josef Brandauer, Candace N Receno, Cynthia Anyaoku, Lauren E Cooke, Hannalyn M Schwarzer, Keith C DeRuisseau, Caitlin M Cunningham, Lara R DeRuisseau

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm2), left ventricular area end diastole (mm2), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.

唐氏综合征(Ds)与出生时的先天性心脏缺陷有关,但老年时的心脏功能尚未得到评估。我们使用Ds模型Ts65Dn小鼠,用超声心动图量化18月龄雄性Ts65Dn小鼠和WT小鼠的心脏结构和功能。我们研究了心脏重量、烟酰胺腺嘌呤二核苷酸(NAD)信号和线粒体(柠檬酸合成酶)活性,因为这些途径可能与Ds的心脏病理有关。与WT相比,Ts65Dn组左心室体积更小,两次舒张期左心室前壁厚度(LVAW_d;mm)和收缩期(LVAW_s;Mm),超声心动图评估。其他功能指标组间相似,包括左室收缩期末期面积(mm2)、左室舒张末期面积(mm2)、左室收缩期末期直径(mm)、左室舒张末期直径(mm)、等容松弛时间(ms)、二尖瓣心房峰值速度(mm/s)、二尖瓣早期峰值速度(mm/s)、心房与早期峰值速度之比(E/A)、心率(bpm)、射血分数(%)和缩短分数(%)。与WT小鼠相比,Ts65Dn小鼠左心室烟酰胺磷酸核糖基转移酶(NAMPT)蛋白表达、NAD浓度和组织重量均较低。各组间Sirtuin 3 (SIRT3)蛋白表达及柠檬酸合成酶活性无显著差异。虽然男性Ts65Dn患者的心脏功能一般保持不变,但心脏大小的改变和生物能量紊乱可能导致Ds患者的衰老差异。
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引用次数: 0
Exertional heat stroke causes long-term skeletal muscle epigenetic reprogramming, altered gene expression, and impaired satellite cell function in mice. 劳累性中暑导致小鼠骨骼肌长期表观遗传重编程、基因表达改变和卫星细胞功能受损。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00226.2023
Kevin O Murray, Jason O Brant, Ray A Spradlin, Trace Thome, Orlando Laitano, Terence E Ryan, Alberto Riva, Michael P Kladde, Thomas L Clanton

The effect of exertional heat stroke (EHS) exposure on skeletal muscles is incompletely understood. Muscle weakness is an early symptom of EHS but is not considered a major target of multiorgan injury. Previously, in a preclinical mouse model of EHS, we observed the vulnerability of limb muscles to a second EHS exposure, suggesting hidden processes contributing to declines in muscle resilience. Here, we evaluated the possible molecular origins of EHS-induced declines in muscle resilience. Female C57BL/6 mice [total n = 56; 28/condition, i.e., EHS and exercise control (EXC)] underwent forced wheel running at 37.5°C/40% relative humidity until symptom limitation (unconsciousness). EXC mice exercised identically at room temperature (22-23°C). After 1 mo of recovery, the following were assessed: 1) specific force and caffeine-induced contracture in soleus (SOL) and extensor digitorum longus (EDL) muscles; 2) transcriptome and DNA methylome responses in gastrocnemius (GAST); and 3) primary satellite cell function (proliferation and differentiation). There were no differences in specific force in either SOL or EDL from EXC. Only EHS solei exhibited lower caffeine sensitivity. EHS GAST exhibited higher RNA expression of genes encoding structural proteins of slow fibers, heat shock proteins, and myogenesis. A total of ∼2,500 differentially methylated regions of DNA that could potentially affect many cell functions were identified. Primary satellite cells exhibited suppressed proliferation rates but normal differentiation responses. Results demonstrate long-term changes in skeletal muscles 1 mo after EHS that could contribute to declines in muscle resilience. Skeletal muscle may join other, more recognized tissues considered vulnerable to long-term effects of EHS.NEW & NOTEWORTHY Exertional heat stroke (EHS) in mice induces long-term molecular and functional changes in limb muscle that could reflect a loss of "resilience" to further stress. The phenotype was characterized by altered caffeine sensitivity and suppressed satellite cell proliferative potential. This was accompanied by changes in gene expression and DNA methylation consistent with ongoing muscle remodeling and stress adaptation. We propose that EHS may induce a prolonged vulnerability of skeletal muscle to further stress or injury.

劳累性中暑(EHS)暴露对骨骼肌的影响尚不完全清楚。肌肉无力是EHS的早期症状,但不被认为是多器官损伤的主要目标。此前,在EHS的临床前小鼠模型中,我们观察到肢体肌肉对第二次EHS暴露的易感性,这表明隐藏的过程导致了肌肉恢复能力的下降。在这里,我们评估了ehs诱导的肌肉恢复力下降的可能分子起源。雌性C57BL/6小鼠[总n =56;28/条件,即EHS和运动控制(EXC)]在37.5°C/40%相对湿度下进行强制车轮运行,直到症状限制(无意识)。EXC小鼠在室温(22-23℃)下运动相同。恢复一个月后,进行以下评估:(1)比目鱼肌(SOL)和指长伸肌(EDL)肌肉的比力和咖啡因引起的挛缩;(2)腓肠肌(GAST)的转录组和DNA甲基组反应;(3)初级卫星细胞功能(增殖和分化)。与EXC相比,SOL和EDL的比力没有差异,只有EHS solei对咖啡因的敏感性较低。EHS GAST表现出较高的慢纤维结构蛋白、热休克蛋白和肌生成基因的RNA表达。总共鉴定了约2500个可能影响许多细胞功能的DNA差异甲基化区域。原代卫星细胞增殖速率受到抑制,但分化反应正常。结果表明,EHS后一个月骨骼肌的长期变化可能导致肌肉弹性下降。骨骼肌可能会加入其他更容易受到EHS长期影响的组织。
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引用次数: 0
Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning. 间歇性常压缺氧改变肥胖个体的底物分配和肌肉氧合:对脂肪燃烧的影响。
IF 2.8 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00153.2023
Guillaume Costalat, Frederic Lemaitre, Sandra Ramos, Gillian M C Renshaw

This single-blind, crossover study aimed to measure and evaluate the short-term metabolic responses to continuous and intermittent hypoxic patterns in individuals with obesity. Indirect calorimetry was used to quantify changes in resting metabolic rate (RMR), carbohydrate (CHOox, %CHO), and fat oxidation (FATox, %FAT) in nine individuals with obesity pre and post: 1) breathing normoxic air [normoxic sham control (NS-control)], 2) breathing continuous hypoxia (CH), or 3) breathing intermittent hypoxia (IH). A mean peripheral oxygen saturation ([Formula: see text]) of 80-85% was achieved over a total of 45 min of hypoxia. Throughout each intervention, pulmonary gas exchanges, oxygen consumption (V̇o2) carbon dioxide production (V̇co2), and deoxyhemoglobin concentration (Δ[HHb]) in the vastus lateralis were measured. Both RMR and CHOox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all P > 0.05). Conversely, a significant increase in FATox was evident between pre- and post-IH (+44%, P = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (P < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (P = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FATox measured pre- and postintervention. It is suggested that during IH, the increased bouts of muscle hypoxia, revealed by elevated Δ[HHb], coupled with cyclic periods of excess posthypoxia oxygen consumption (EPHOC, inherent to the intermittent pattern) played a significant role in driving the increase in FATox post-IH.

这项单盲交叉研究旨在测量和评估肥胖患者对持续和间歇性缺氧模式的短期代谢反应。采用间接量热法量化9例肥胖患者静息代谢率(RMR)、碳水化合物(chox, %CHO)和脂肪氧化(FATox, % fat)在以下前后的变化:(i)呼吸常压空气[常压假对照(NS-control)];(ii)呼吸持续缺氧(CH);或(iii)间歇性缺氧(IH)。在45分钟的缺氧时间内,平均外周氧饱和度(SpO2)达到80-85%。在每次干预过程中,测量肺气体交换——耗氧量()、二氧化碳产生()和股外侧肌脱氧血红蛋白浓度([hbb])。每次治疗后,干预前和干预后的RMR和chox测量结果都没有变化:CH;或IH(均p > 0.05)。相反,在ih前后,FATox显著增加(+44%,p = 0.048)。虽然平均[hbb]值在IH和CH期间显著增加(p),但与CH相比,IH达到了[hbb]的最大顶点(p = 0.002)。此外,干预前后测得的FATox变化与∆[hbb]呈正相关。这表明,在IH期间,肌肉缺氧次数的增加(表现为升高的∆[hbb]),加上缺氧后过量氧气消耗的循环周期(EPHOC,固有的间歇性模式)在推动IH后FATox的增加中发挥了重要作用。
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引用次数: 0
Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation. 耐缺氧鲫鱼脑部在缺氧-再氧合过程中脯氨酰羟化酶域(PHDs)(HIF 的上游调节因子)的表达。
IF 2.8 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-12-25 DOI: 10.1152/ajpregu.00211.2023
Lucie Gerber, Julien Resseguier, Tellef Helle-Valle, Elie Farhat, Göran E Nilsson, Sjannie Lefevre

The hypoxia-inducible factor (HIF) is considered key in the transcriptional response to low oxygen. Yet, the role of HIF in the absence of oxygen (anoxia) and in preparation for reoxygenation remains unclear. Recent studies suggest that mounting a HIF response may be counterproductive for anoxia survival. We here studied one of the champions of anoxia survival, the crucian carp (Carassius carassius), and hypothesized that expression of prolyl hydroxylase domains (PHDs; the upstream regulators of HIF) are upregulated to circumvent an energy-costly activation of HIF in anoxia and to prepare for reoxygenation. We measured whole brain mRNA and protein levels of the three isoforms PHD1, PHD2, and PHD3, coded for by multiple paralogs of the genes egln2, egln1, and egln3, using quantitative PCR and Western blotting in the brain of crucian carps exposed to 5 days normoxia or anoxia, and 5 days anoxia followed by 3 or 24 h of reoxygenation. The mRNA levels of most egln paralogs were increased in anoxia and upon reoxygenation, with egln3 showing the largest increase in mRNA level (up to 17-fold) and highest relative mRNA abundance (up to 75% of expressed egln). The protein level of all PHDs was maintained in anoxia and increased upon reoxygenation. We then explored PHD distribution in different brain regions and found PHD immunoreactivity to be associated with axonal branches and showing region-specific changes during anoxia-reoxygenation. Our results support an overall upregulation of egln under prolonged anoxia and PHDs upon reoxygenation in crucian carp, likely aimed at suppressing HIF responses, although regional differences are apparent in such a complex organ as the brain.NEW & NOTEWORTHY We report a profound upregulation of most egln paralog mRNA levels in anoxia and upon reoxygenation, with egln3ii showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.

低氧诱导因子(HIF)被认为是低氧转录反应的关键。然而,HIF 在缺氧(缺氧)和准备复氧时的作用仍不清楚。最近的研究表明,启动 HIF 响应可能会对缺氧生存产生反作用。我们在此研究了缺氧生存冠军鲫鱼(Carassius carassius),并假设脯氨酰羟化酶结构域 PHDs(HIF 的上游调节因子)的表达会上调,以规避缺氧状态下 HIF 高能耗的激活,并为复氧做好准备。我们使用 qPCR 和 Western 印迹技术测量了暴露于 5 天常氧或缺氧以及 5 天缺氧后 3 小时或 24 小时复氧的鲫鱼大脑中 PHD1、2 和 3 三种异构体(由 egln2、1 和 3 基因的多个旁系亲属编码)的 mRNA 和蛋白质水平。大多数egln旁系亲属的mRNA水平在缺氧和复氧时都有所增加,其中egln3的mRNA水平增幅最大(高达20倍),相对mRNA丰度也最高(高达所表达eglns的75%)。在缺氧状态下,所有 PHDs 的蛋白水平均保持不变,而在复氧后则有所提高。我们随后探究了PHDs在不同脑区的分布,发现PHDs免疫反应与轴突分支相关,并在缺氧-复氧过程中表现出区域特异性变化。我们的研究结果表明,在鲫鱼长期缺氧的情况下,eglns总体上调,而在复氧时,PHDs上调,其目的可能是抑制HIF反应,尽管在大脑这样一个复杂的器官中,区域差异是显而易见的。
{"title":"Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation.","authors":"Lucie Gerber, Julien Resseguier, Tellef Helle-Valle, Elie Farhat, Göran E Nilsson, Sjannie Lefevre","doi":"10.1152/ajpregu.00211.2023","DOIUrl":"10.1152/ajpregu.00211.2023","url":null,"abstract":"<p><p>The hypoxia-inducible factor (HIF) is considered key in the transcriptional response to low oxygen. Yet, the role of HIF in the absence of oxygen (anoxia) and in preparation for reoxygenation remains unclear. Recent studies suggest that mounting a HIF response may be counterproductive for anoxia survival. We here studied one of the champions of anoxia survival, the crucian carp (<i>Carassius carassius</i>), and hypothesized that expression of prolyl hydroxylase domains (PHDs; the upstream regulators of HIF) are upregulated to circumvent an energy-costly activation of HIF in anoxia and to prepare for reoxygenation. We measured whole brain mRNA and protein levels of the three isoforms PHD1, PHD2, and PHD3, coded for by multiple paralogs of the genes <i>egln2</i>, <i>egln1</i>, and <i>egln3</i>, using quantitative PCR and Western blotting in the brain of crucian carps exposed to 5 days normoxia or anoxia, and 5 days anoxia followed by 3 or 24 h of reoxygenation. The mRNA levels of most <i>egln</i> paralogs were increased in anoxia and upon reoxygenation, with <i>egln3</i> showing the largest increase in mRNA level (up to 17-fold) and highest relative mRNA abundance (up to 75% of expressed <i>egln</i>). The protein level of all PHDs was maintained in anoxia and increased upon reoxygenation. We then explored PHD distribution in different brain regions and found PHD immunoreactivity to be associated with axonal branches and showing region-specific changes during anoxia-reoxygenation. Our results support an overall upregulation of <i>egln</i> under prolonged anoxia and PHDs upon reoxygenation in crucian carp, likely aimed at suppressing HIF responses, although regional differences are apparent in such a complex organ as the brain.<b>NEW & NOTEWORTHY</b> We report a profound upregulation of most <i>egln</i> paralog mRNA levels in anoxia and upon reoxygenation, with <i>egln3ii</i> showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. 高斯白噪声输入下压力反射神经弧传递特性的输入大小依赖性。
IF 2.8 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00199.2023
Toru Kawada, Tadayoshi Miyamoto, Masafumi Fukumitsu, Keita Saku

Although Gaussian white noise (GWN) inputs offer a theoretical framework for identifying higher-order nonlinearity, an actual application to the data of the neural arc of the carotid sinus baroreflex did not succeed in fully predicting the well-known sigmoidal nonlinearity. In the present study, we assumed that the neural arc can be approximated by a cascade of a linear dynamic (LD) component and a nonlinear static (NS) component. We analyzed the data obtained using GWN inputs with a mean of 120 mmHg and standard deviations (SDs) of 10, 20, and 30 mmHg for 15 min each in anesthetized rats (n = 7). We first estimated the linear transfer function from carotid sinus pressure to sympathetic nerve activity (SNA) and then plotted the measured SNA against the linearly predicted SNA. The predicted and measured data pairs exhibited an inverse sigmoidal distribution when grouped into 10 bins based on the size of the linearly predicted SNA. The sigmoidal nonlinearity estimated via the LD-NS model showed a midpoint pressure (104.1 ± 4.4 mmHg for SD of 30 mmHg) lower than that estimated by a conventional stepwise input (135.8 ± 3.9 mmHg, P < 0.001). This suggests that the NS component is more likely to reflect the nonlinearity observed during pulsatile inputs that are physiological to baroreceptors. Furthermore, the LD-NS model yielded higher R2 values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset.NEW & NOTEWORTHY We examined the input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. A linear dynamic-static nonlinear model yielded higher R2 values compared with a linear model and captured the well-known sigmoidal nonlinearity of the neural arc, indicating that the nonlinear dynamics contributed to determining sympathetic nerve activity. Ignoring such nonlinear dynamics might reduce our ability to explain underlying physiology and significantly limit the interpretation of experimental data.

尽管高斯白噪声(GWN)输入为识别高阶非线性提供了理论框架,但对颈动脉窦压力反射神经弧数据的实际应用并不能成功地完全预测众所周知的s型非线性。在本研究中,我们假设神经弧可以用线性动态(LD)分量和非线性静态(NS)分量的级联来近似。我们分析了麻醉大鼠(n = 7)使用GWN输入(平均120 mmHg,标准差10、20和30 mmHg,各15分钟)获得的数据。我们首先估计了颈动脉窦压到交感神经活动(SNA)的线性传递函数,然后绘制了测量的SNA与线性预测的SNA的对比图。根据线性预测SNA的大小,将预测和测量的数据对分成10个箱时,呈现逆s型分布。通过LD-NS模型估计的s型非线性显示,SD为30 mmHg时,中点压力(104.1±4.4 mmHg)低于传统逐步输入估计的中点压力(135.8±3.9 mmHg, P < 0.001)。这表明,NS成分更有可能反映在脉动输入期间观察到的非线性,这对压力感受器来说是生理的。此外,在测试数据集中,LD-NS模型比线性模型和先前建议的二阶Uryson模型产生更高的R2值。
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引用次数: 0
Differences in the range of thermoneutral zone between mouse strains: potential effects on translational research. 小鼠品系间热中性区范围的差异-对转译研究的潜在影响。
IF 2.8 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-11-27 DOI: 10.1152/ajpregu.00154.2023
Andrzej K Gębczyński, Julita Sadowska, Marek Konarzewski

Laboratory mice are commonly used for studies emulating human metabolism. To render human energetics, their ratio of daily (DEE) to basal (BMR) energy expenditure of 1.7-1.8 should be maintained. However, the DEE/BMR ratio strongly depends on whether a given study using a mouse model is carried out above, or below the lower critical temperature (LCT) of the thermoneutral zone, which is rarely considered in translational research. Here, we used mice artificially selected for high or low rates of BMR along with literature data to analyze the effect of ambient temperature on possible systematic bias in DEE/BMR. We demonstrated that the estimated LCTs of mice from the high and low BMR lines differ by more than 7°C. Furthermore, the range of variation of LCTs of mouse strains used in translational research spans from 23 to 33°C. Differences between LCTs in our selected mice and other mouse strains are mirrored by differences in their DEE-to-BMR ratio, on average increasing it at the rate of 0.172°C-1 at temperatures below LCT. Given the wide range of LCTs in different mouse strains, we conclude that the energetic cost of thermoregulation may differ greatly for different mouse strains with a potentially large impact on translational outcomes. Thus, the LCT of a given mouse strain is an important factor that must be considered in designing translational studies.

实验室小鼠通常用于模拟人体代谢的研究。为了提供人体能量,他们的每日(DEE)与基础(BMR)能量消耗的比率应保持在1.7-1.8。然而,DEE/BMR比率在很大程度上取决于使用小鼠模型的给定研究是否高于或低于热中性区的较低临界温度(LCT),这在转化研究中很少考虑。在这里,我们使用人工选择的高或低BMR率的小鼠以及文献数据来分析环境温度对DEE/BMR可能的系统偏差的影响。我们证明,来自高BMR和低BMR系的小鼠的估计lct相差超过7°C。此外,用于转化研究的小鼠品系的LCTs变化范围为23至33°C。我们所选小鼠的LCT与其他小鼠品系的差异反映在它们的DEE/BMR比率的差异上,在低于LCT的温度下,其平均增加率为0.172°C-1。鉴于不同小鼠品系的lct范围广泛,我们得出结论,不同小鼠品系的体温调节的能量成本可能存在很大差异,这可能对翻译结果产生很大影响。因此,给定小鼠品系的LCT是设计转译研究时必须考虑的一个重要因素。
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引用次数: 0
Muscle metaboreflex stimulates the cardiac sympathetic afferent reflex causing positive feedback amplification of sympathetic activity: effect of heart failure. 肌肉代谢反射刺激心脏交感神经传入反射,引起交感神经活动的正反馈放大:心力衰竭效应。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-27 DOI: 10.1152/ajpregu.00235.2023
Joseph Mannozzi, Danielle Senador, Jasdeep Kaur, Matthew Gross, Megan McNitt, Alberto Alvarez, Beruk Lessanework, Donal S O'Leary

Exercise intolerance is a hallmark symptom of heart failure and to a large extent stems from reductions in cardiac output that occur due to the inherent ventricular dysfunction coupled with enhanced muscle metaboreflex-induced functional coronary vasoconstriction, which limits increases in coronary blood flow. This creates a further mismatch between O2 delivery and O2 demand, which may activate the cardiac sympathetic afferent reflex (CSAR), causing amplification of the already increased sympathetic activity in a positive-feedback fashion. We used our chronically instrumented conscious canine model to evaluate if chronic ablation of afferents responsible for the CSAR would attenuate the gain of muscle metaboreflex before and after induction of heart failure. After afferent ablation, the gain of the muscle metaboreflex control of mean arterial pressure was significantly reduced before (-239.5 ± 16 to -95.2 ± 8 mmHg/L/min) and after the induction of heart failure (-185.6 ± 14 to -95.7 ± 12 mmHg/L/min). Similar results were observed for the strength (gain) of muscle metaboreflex control of heart rate, cardiac output, and ventricular contractility. Thus, we conclude that the CSAR contributes significantly to the strength of the muscle metaboreflex in normal animals with heart failure serving as an effective positive-feedback amplifier thereby further increasing sympathetic activity.NEW & NOTEWORTHY The powerful pressor responses from the CSAR arise via O2 delivery versus O2 demand imbalance. Muscle metaboreflex activation (MMA) simultaneously elicits coronary vasoconstriction (which is augmented in heart failure) and profound increases in cardiac work thereby upsetting oxygen balance. Whether MMA activates the CSAR thereby amplifying MMA responses is unknown. We observed that removal of the CSAR afferents attenuated the strength of the muscle metaboreflex in normal and subjects with heart failure.

运动不耐受是心力衰竭的一个标志性症状,在很大程度上源于心输出量的减少,这是由于固有的心室功能障碍加上肌肉代谢反射增强引起的功能性冠状动脉血管收缩,从而限制了冠状动脉血流的增加。这造成了氧气输送和氧气需求之间的进一步不匹配,这可能会激活心脏交感传入反射(CSAR),导致已经增加的交感神经活动以正反馈的方式放大。我们利用我们的长期有意识的犬模型来评估慢性消融负责CSAR的传入神经是否会减弱诱发心力衰竭前后肌肉代谢反射的增加。传入消融术后,肌肉代谢反射控制的平均动脉压增益在诱发心力衰竭前(-239.5±16 ~ -95.2±8 mmHg/l/min)和诱导心力衰竭后(-185.6±14 ~ -95.7±12 mmHg/l/min)显著降低。在心率、心输出量和心室收缩力的肌肉代谢反射控制的强度(增益)方面也观察到类似的结果。因此,我们得出结论,在正常和心力衰竭动物中,CSAR作为有效的正反馈放大器,对肌肉代谢反射的强度有显著贡献,从而进一步增加交感神经活动。
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引用次数: 0
Pseudocannabinoid H4CBD improves glucose response during advanced metabolic syndrome in OLETF rats independent of increase in insulin signaling proteins. 伪大麻素H4CBD改善OLETF大鼠晚期代谢综合征期间的葡萄糖反应,与胰岛素信号蛋白的增加无关。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-10-30 DOI: 10.1152/ajpregu.00125.2022
Jessica N Wilson, Dora A Mendez, Francis Dhoro, Nikolay Shevchenko, Mark Mascal, Kyle Lund, Robert Fitzgerald, Nicholas V DiPatrizio, Rudy M Ortiz

Cannabidiol (CBD) use has grown exponentially more popular in the last two decades, particularly among older adults (>55 yr), though very little is known about the effects of CBD use during age-associated metabolic dysfunction. In addition, synthetic analogues of CBD have generated great interest because they can offer a chemically pure product, which is free of plant-associated contaminants. To assess the effects of a synthetic analogue of CBD (H4CBD) on advanced metabolic dysfunction, a cohort of 41-wk-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered 200 mg H4CBD/kg by oral gavage for 4 wk. Animals were fed ad libitum and monitored alongside vehicle-treated OLETF and Long-Evans Tokushima Otsuka (LETO) rats, the lean-strain controls. An oral glucose-tolerance test (oGTT) was performed after 4 wk of treatment. When compared with vehicle-treated, OLETF rats, H4CBD decreased body mass (BM) by 15%, which was attributed to a significant loss in abdominal fat. H4CBD reduced glucose response (AUCglucose) by 29% (P < 0.001) and insulin resistance index (IRI) by 25% (P < 0.05) compared with OLETF rats. However, H4CBD did not statically reduce fasting blood glucose or plasma insulin, despite compensatory increases in skeletal muscle native insulin receptor (IR) protein expression (54%; P < 0.05). H4CBD reduced circulating adiponectin (40%; P < 0.05) and leptin (47%; P < 0.05) and increased ghrelin (75%; P < 0.01) compared with OLETF. Taken together, a chronic, high dose of H4CBD may improve glucose response, independent of static changes in insulin signaling, and these effects are likely a benefit of the profound loss of visceral adiposity.NEW & NOTEWORTHY Cannabis product use has grown in the last two decades despite the lack of research on Cannabidiol (CBD)-mediated effects on metabolism. Here, we provide seminal data on CBD effects during age-associated metabolic dysfunction. We gave 41-wk-old OLETF rats 200 mg H4CBD/kg by mouth for 4 wk and noted a high dose of H4CBD may improve glucose response, independent of static changes in insulin signaling, and these effects are likely a benefit of loss of visceral adiposity.

在过去的二十年里,大麻二酚(CBD)的使用呈指数级增长,尤其是在老年人(>55岁)中,尽管人们对CBD在年龄相关代谢功能障碍期间的影响知之甚少。此外,CBD的合成类似物也引起了人们的极大兴趣,因为它们可以提供一种化学纯的产品,不含植物相关污染物。为了评估CBD的合成类似物(H4CBD)对晚期代谢功能障碍的影响,一组41周大的Otsuka Long Evans Tokushima Fatty(OLETF)大鼠通过灌胃给药200mg H4CBD/kg,持续4周。随意喂养动物,并与载体处理的OLETF和Long-Evans-Tokushima Otsuka(LETO)大鼠(瘦品系对照)一起监测。治疗4周后进行口服葡萄糖耐量试验(oGTT)。与载体处理的OLETF大鼠相比,H4CBD使体重(BM)减少了15%,这归因于腹部脂肪的显著减少。H4CBD降低了29%的葡萄糖反应(AUC葡萄糖)(p
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引用次数: 0
Relationship between red blood cell lifespan and endogenous carbon monoxide in the common bottlenose dolphin and beluga. 宽吻海豚和白鲸红细胞寿命与内源性一氧化碳的关系。
IF 2.8 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-11-20 DOI: 10.1152/ajpregu.00172.2023
Anna B Pearson, Luis A Hückstädt, Stephen T Kinsey, Todd L Schmitt, Todd R Robeck, Judy St Leger, Paul J Ponganis, Michael S Tift

Certain deep-diving marine mammals [i.e., northern elephant seal (Mirounga angustirostris), Weddell seal (Leptonychotes weddellii)] have blood carbon monoxide (CO) levels that are comparable with those of chronic cigarette smokers. Most CO produced in humans is a byproduct of heme degradation, which is released when red blood cells (RBCs) are destroyed. Elevated CO can occur in humans when RBC lifespan decreases. The contribution of RBC turnover to CO concentrations in marine mammals is unknown. Here, we report the first RBC lifespans in two healthy marine mammal species with different diving capacities and heme stores, the shallow-diving bottlenose dolphin (Tursiops truncatus) and deep-diving beluga whale (Delphinapterus leucas), and we relate the lifespans to the levels of CO in blood and breath. The belugas, with high blood heme stores, had the longest mean RBC lifespan compared with humans and bottlenose dolphins. Both cetacean species were found to have three times higher blood CO content compared with humans. The estimated CO production rate from heme degradation indicates some marine mammals may have additional mechanisms for CO production, or delay CO removal from the body, potentially from long-duration breath-holds.NEW & NOTEWORTHY This is the first study to determine the red blood cell lifespan in a marine mammal species. High concentrations of carbon monoxide (CO) were found in the blood of bottlenose dolphins and in the blood and breath of belugas compared with healthy humans. Red blood cell turnover accounted for these high levels in bottlenose dolphins, but there may be alternative mechanisms of endogenous CO production that are contributing to the CO concentrations observed in belugas.

某些深潜海洋哺乳动物(如北象海豹(miounga angustirosis),威德尔海豹(Leptonychotes weddellii))的血液一氧化碳(CO)水平与慢性吸烟者相当。人体内产生的大部分一氧化碳是血红素降解的副产物,血红素在红细胞被破坏时释放出来。当红细胞寿命缩短时,人体内可出现CO升高。海洋哺乳动物的红细胞周转对CO浓度的贡献尚不清楚。在这里,我们首次报道了两种具有不同潜水能力和血红素储存的健康海洋哺乳动物——浅潜宽吻海豚(Tursiops truncatus)和深潜白鲸(Delphinapterus leucas)的红细胞寿命,并将其寿命与血液和呼吸中的CO水平联系起来。与人类和宽吻海豚相比,血血红素储量高的白鲸的平均红细胞寿命最长。这两种鲸类动物的血液CO含量都是人类的三倍。血红素降解产生CO的估计速率表明,一些海洋哺乳动物可能具有额外的CO产生机制,或可能通过长时间屏气延迟CO从体内排出。
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引用次数: 0
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American journal of physiology. Regulatory, integrative and comparative physiology
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