American journal of physiology. Regulatory, integrative and comparative physiology最新文献

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Determining autonomic sympathetic tone and reactivity using Baevsky's stress index. 利用baevsky应激指数测定自主交感神经张力和反应性。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-02-27 DOI: 10.1152/ajpregu.00243.2024
Jan D Huizinga, Ji-Hong Chen, Amer Hussain, Difei Zheng, Lijun Liu, Hansel Lui, Maxwell Pan, Xurui Chen, Brienna DiBattista, Marzia Alam, Julia Niro
{"title":"Determining autonomic sympathetic tone and reactivity using Baevsky's stress index.","authors":"Jan D Huizinga, Ji-Hong Chen, Amer Hussain, Difei Zheng, Lijun Liu, Hansel Lui, Maxwell Pan, Xurui Chen, Brienna DiBattista, Marzia Alam, Julia Niro","doi":"10.1152/ajpregu.00243.2024","DOIUrl":"10.1152/ajpregu.00243.2024","url":null,"abstract":"<p><p>The extrinsic autonomic nervous system is critical in controlling most organ functions and is involved in the pathophysiology of many chronic diseases. However, its assessment plays a minor role in the clinical practice of diagnosis and treatment outside cardiology. Since sympathetic dysfunction is related to diseases such as diabetes, chronic stress, and urinary and gastrointestinal motor dysfunction, an autonomic assessment is warranted. Here, we evaluate the Baevsky stress index (SI) to assess sympathetic tone and reactivity based on heart rate variability. We start with discussing Baevsky's original stress index. We propose an optimized calculation of SI and assess the SI of 73 self-declared healthy subjects in the age groups 16-35 yr, 35-50 yr, and 50+ yr at supine baseline and in response to postural change from supine to standing. Normality assessment and kernel density analysis identified two subgroups: one we deemed to have normal autonomic functioning, and an outlier group with significantly higher baseline sympathetic index (SI) and sympathetic reactivity to standing. Using a Gaussian mixture model, we determined normal SI values and values for autonomic stress and autonomic dysfunction. This study provides a needed start to evaluate sympathetic dysfunction using heart rate variability.<b>NEW & NOTEWORTHY</b> To help diagnose autonomic dysfunction in chronic diseases, Baevsky's stress index is evaluated for the assessment of sympathetic tone and reactivity. Ranges of control values are given for different age groups, and significant differences are shown with patients with chronic gastrointestinal motility disorders.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R562-R577"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514413","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
Sleep tight with vitamin D's might. 睡个好觉,补充维生素D。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1152/ajpregu.00058.2025
John J Durocher, Ezra Mutai
{"title":"Sleep tight with vitamin D's might.","authors":"John J Durocher, Ezra Mutai","doi":"10.1152/ajpregu.00058.2025","DOIUrl":"10.1152/ajpregu.00058.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R557-R558"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708228","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
MLO-Y4 fluid flow shear stress conditioned media enhances cardiac contractility and intracellular Ca2. MLO-Y4流体流动剪切应力调节介质增强心脏收缩性和细胞内Ca2。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1152/ajpregu.00287.2024
Anuhya Dayal, Mark Gray, Julian A Vallejo, Nuria Lara-Castillo, Mark L Johnson, Michael J Wacker
{"title":"MLO-Y4 fluid flow shear stress conditioned media enhances cardiac contractility and intracellular Ca<sup>2</sup>.","authors":"Anuhya Dayal, Mark Gray, Julian A Vallejo, Nuria Lara-Castillo, Mark L Johnson, Michael J Wacker","doi":"10.1152/ajpregu.00287.2024","DOIUrl":"10.1152/ajpregu.00287.2024","url":null,"abstract":"<p><p>The skeleton is in complex interplay with the other systems of the body and is highly responsive to input from the external environment. Bone mechanical loading results in interstitial fluid flow via the lacunar-canalicular system, generating fluid flow sheer stress (FFSS). FFSS variably stresses osteocytes, subsequently causing the release of metabolites and protein factors that function locally to increase bone formation and may play a role in cross talk between various organ systems, for instance between bone and skeletal muscle. Therefore, we hypothesized that this cross talk includes altering cardiac function. To test this hypothesis, media conditioned by MLO-Y4 osteocyte-like cell culture line under FFSS was used to model the endocrine effects of bone during mechanical loading on contraction of ex vivo Langendorf-perfused isolated hearts. When hearts were externally paced at a fixed rate, FFSS osteocyte conditioned media (CM) induced significant premature contractions compared with vehicle (control). FFSS osteocyte CM administration to self-paced hearts increased total contraction force by 31%. To determine whether the mechanism involved intracellular Ca<sup>2+</sup>, vehicle and FFSS bone CM were perfused over cultured H9C2 cardiomyocytes while undergoing Ca<sup>2+</sup> imaging using Fluo-8. We observed an increase in intracellular Ca<sup>2+</sup> with FFSS CM perfusion of cardiomyocytes compared with vehicle. These increases were only present with exogenous electrical pacing. Our findings demonstrate that FFSS bone CM enhances cardiac contractility by increasing intracellular cardiomyocyte Ca<sup>2+</sup>. The results obtained in this study suggest that the skeleton, responding to mechanical strain, has the potential to augment cardiac output and provide evidence for bone-heart cross talk.<b>NEW & NOTEWORTHY</b> The skeletal system operates as an endocrine organ, releasing factors that impact multi-tissue physiology. The results obtained in this study demonstrate that conditioned media collected from MLO-Y4 osteocytes exposed to fluid flow shear stress increases cardiomyocyte intracellular calcium and enhances cardiac contractility in vitro. These results support the concept of bone-heart cross talk that may have implications in exercise training, reduced-function settings such as bedrest, and the interplay between bone and heart health.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R591-R600"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708226","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
Cardiac autonomic function in young, healthy adults: Influence of race and sex. 年轻健康成人心脏自主神经功能:种族和性别的影响
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.1152/ajpregu.00288.2024
Ziba Taherzadeh, Claire E Kissell, Benjamin E Young, Taha A Alhalimi, Brandi Y Stephens, Jasdeep Kaur, Yungfei Kao, R Matthew Brothers, Paul J Fadel
{"title":"Cardiac autonomic function in young, healthy adults: Influence of race and sex.","authors":"Ziba Taherzadeh, Claire E Kissell, Benjamin E Young, Taha A Alhalimi, Brandi Y Stephens, Jasdeep Kaur, Yungfei Kao, R Matthew Brothers, Paul J Fadel","doi":"10.1152/ajpregu.00288.2024","DOIUrl":"10.1152/ajpregu.00288.2024","url":null,"abstract":"<p><p>Non-Hispanic Black (BL) adults living in the United States are more likely to develop cardiovascular disease (CVD) compared with their non-Hispanic White (WH) counterparts. Although measures of cardiac autonomic function [i.e., spontaneous cardiac baroreflex sensitivity (BRS) and heart rate variability (HRV)] have a predictive value for CVD, studies investigating racial differences in cardiac autonomic function are limited and have reported conflicting results. Furthermore, sex differences are often not considered despite BL women having a high prevalence of CVD. We hypothesized that young BL men and women would exhibit lower cardiac BRS and HRV compared with their WH counterparts. Heart rate and beat-to-beat blood pressure were continuously recorded during 5 min of supine rest in 145 young (18-33 yr), healthy, BL (37 men, 38 women) and WH (39 men, 31 women) adults to assess cardiac BRS and HRV. Overall cardiac BRS (sequence method) was higher in BL adults compared with WH adults (<i>P</i> < 0.001), which was mainly driven by differences between BL and WH men (BL men: 34 ± 16 vs. WH men: 21 ± 9 ms/mmHg, <i>P</i> < 0.001) compared with women (BL women: 27 ± 12 vs. WH women: 24 ± 11 ms/mmHg; <i>P</i> > 0.05). Likewise, greater HRV in BL adults, indexed by root mean square of successive differences, was primarily driven by BL men (BL men: 109 ± 59 vs. WH men: 64 ± 33 ms; <i>P</i> < 0.001) rather than BL women (<i>P</i> > 0.05). Thus, contrary to our hypothesis, these results support that reduced cardiac autonomic function does not manifest early in life among young BL adults.<b>NEW & NOTEWORTHY</b> Herein, we demonstrated that BL adults do not have lower cardiac autonomic function compared with WH adults. Rather BL men had greater spontaneous cardiac baroreflex sensitivity and heart rate variability compared with WH men while no differences were found among BL and WH women. These findings suggest that reduced cardiac autonomic function, which could increase the risk of cardiovascular disease, does not appear early in life in healthy BL adults.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R611-R618"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787518","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
Serum cytokines and their soluble receptors are differently regulated between trained and untrained men after vigorous endurance exercise. 在剧烈耐力运动后,经过训练和未经训练的男性血清细胞因子及其可溶性受体的调节不同。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1152/ajpregu.00010.2025
Jeremy B Ducharme, Jonathan W Specht, Alyssa R Bailly, Michael R Deyhle
{"title":"Serum cytokines and their soluble receptors are differently regulated between trained and untrained men after vigorous endurance exercise.","authors":"Jeremy B Ducharme, Jonathan W Specht, Alyssa R Bailly, Michael R Deyhle","doi":"10.1152/ajpregu.00010.2025","DOIUrl":"10.1152/ajpregu.00010.2025","url":null,"abstract":"<p><p>Endurance training contributes to immune system changes that help manage exercise-induced stress and promote an anti-inflammatory effect. However, the specific mechanisms underlying these adaptations are still being explored. Cytokines play a key role in both acute and chronic exercise responses through interactions with their receptors, which are present in both membrane-bound and soluble forms. Yet, the impact of exercise on cytokines and soluble cytokine receptors in parallel remains understudied. Therefore, the purpose of this study was to assess how cytokines and their soluble receptors change in serum after vigorous exercise in endurance-trained and untrained men. Following 1-h of cycling at their respiratory compensation point, untrained men (<i>n</i> = 5) exhibited a significant increase in proinflammatory cytokines, including IL-6, TNF-α, IL-1β, CCL2, and VEGFA. In contrast, anti-inflammatory cytokines such as IL-10 and IL-1Ra were reduced. These effects were not observed in the trained group (<i>n</i> = 7). Instead, proinflammatory cytokine levels remained close to the baseline, whereas the anti-inflammatory cytokines IL-10 and IL-1Ra increased. In the trained group, these cytokine changes were accompanied by a marked increase in the expression of soluble cytokine receptors known to inhibit cytokine-mediated signaling, such as sIL-1RII, sGP130, sTNFRI, sTNFRII, sVEGFR1, and sVEGFR2, indicating reduced cytokine bioavailability. However, in the untrained group, the expression of these soluble cytokine receptors either remained unchanged or decreased, suggesting greater cytokine bioavailability. Together these findings highlight a novel potential anti-inflammatory adaptation such that trained men present a blunted inflammatory response by both reduced inflammatory cytokines and increased soluble cytokine receptors after exercise compared with untrained men.<b>NEW & NOTEWORTHY</b> Our study identifies a novel potential anti-inflammatory adaptation to endurance training, where trained men present a blunted inflammatory response characterized by reduced inflammatory cytokines and increased soluble cytokine receptors, resulting in decreased cytokine bioavailability after exercise compared with untrained men.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R581-R587"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699402","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
The anorexigenic peptide nesfatin-1 dampens the B cell response to receptor-mediated stimulation through inhibition of NF-κB signaling. 厌氧肽nesfatin-1通过抑制NFĸB信号传导抑制B细胞对受体介导的刺激的反应。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1152/ajpregu.00233.2024
Tara L Steffen, Joshua D Stafford, Colleen R Bocke, Willis K Samson, Gina L C Yosten
{"title":"The anorexigenic peptide nesfatin-1 dampens the B cell response to receptor-mediated stimulation through inhibition of NF-κB signaling.","authors":"Tara L Steffen, Joshua D Stafford, Colleen R Bocke, Willis K Samson, Gina L C Yosten","doi":"10.1152/ajpregu.00233.2024","DOIUrl":"10.1152/ajpregu.00233.2024","url":null,"abstract":"<p><p>Nesfatin-1, a posttranslational product of the protein encoded by the nucleobindin 2 gene (NUCB2), was functionally identified as an appetite regulatory molecule in rat hypothalamic nuclei. In the years following the discovery, those findings have been corroborated and expanded upon, and we now know that nesfatin-1 is expressed throughout peripheral tissues and exerts physiological effects beyond feeding control. Literature indicates that adipose tissue is one of the peripheral sources of NUCB2/nesfatin-1, and in this setting, it has anti-inflammatory effects that have recently been implicated in regulating chronic inflammation associated with diet-induced obesity. Currently, there are gaps in our understanding of what cell types within the adipose tissue compartment respond to nesfatin-1, in addition to the cellular mechanism(s) of this peptide. In this study, we sought to determine a mechanism by which this peptide might directly interact with the immune system starting with a human B cell line, Raji. We show that nesfatin-1 inhibits lipopolysaccharide (LPS) and B cell receptor (BCR) dual stimulation-mediated B cell growth, stimulation-induced cell death, and secretion of inflammatory mediators. Specifically, there was a reduced fold-change in B cell growth during stimulation which is paired with a reduction in the formation of apoptotic (annexin V<sup>+</sup>) cells. In addition, nesfatin-1 significantly reduced IgM secretion and modestly reduced TNFα secretion by stimulated B cells. The anti-inflammatory effects of nesfatin-1 overall are likely due to attenuation of NF-κB signaling, via inhibition of IκB degradation, in stimulated B cells.<b>NEW & NOTEWORTHY</b> This study establishes an interaction of nesfatin-1 and a human B cell line, Raji. Nesfatin-1 was shown to limit the B cell response to receptor-mediated stimulation, an action that has potential implications within the immune system and the development of chronic inflammation associated with the obese state. This study, along with previously published works, highlights a need for further research on nesfatin-1's interactions with adipocytes and immune cells.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R601-R610"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708230","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
Possible role of muscle AMP deamination. 肌肉 AMP 脱氨的可能作用:聚焦 "骨骼肌单磷酸肌苷的形成可在体内增量阶跃收缩过程中保护 ∆GATP".
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-27 DOI: 10.1152/ajpregu.00030.2025
Jerzy A Zoladz, Joanna Majerczak, Bernard Korzeniewski
{"title":"Possible role of muscle AMP deamination.","authors":"Jerzy A Zoladz, Joanna Majerczak, Bernard Korzeniewski","doi":"10.1152/ajpregu.00030.2025","DOIUrl":"10.1152/ajpregu.00030.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R588-R590"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727474","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
Sudorific agonist pathways: which direction to take and are there possible interactions? 发汗激动剂途径:采取哪个方向,是否有可能相互作用?
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-04 DOI: 10.1152/ajpregu.00041.2025
Thad E Wilson, Kristen Metzler-Wilson, Kelsey A Bullens
{"title":"Sudorific agonist pathways: which direction to take and are there possible interactions?","authors":"Thad E Wilson, Kristen Metzler-Wilson, Kelsey A Bullens","doi":"10.1152/ajpregu.00041.2025","DOIUrl":"10.1152/ajpregu.00041.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R578-R580"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555508","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
Follow the fat. Regulation of metabolic substrates in trout. 跟着脂肪走。鳟鱼代谢底物的调控。编辑聚焦于“虹鳟鱼的代谢燃料选择:应对脂肪内输注”。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1152/ajpregu.00060.2025
Grant B McClelland, Sulayman A Lyons
{"title":"Follow the fat. Regulation of metabolic substrates in trout.","authors":"Grant B McClelland, Sulayman A Lyons","doi":"10.1152/ajpregu.00060.2025","DOIUrl":"10.1152/ajpregu.00060.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R559-R561"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708224","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
Sex-specific systemic metabolic predictors of resistance to calorie restriction-induced weight loss in obese Diversity Outbred mice. 性别特异性的系统代谢预测因子对卡路里限制引起的肥胖多样性杂交小鼠体重减轻的抵抗。
IF 2.2 3区 医学
American journal of physiology. Regulatory, integrative and comparative physiology Pub Date : 2025-04-18 DOI: 10.1152/ajpregu.00220.2024
Evan M Paules, Melissa VerHague, Anju A Lulla, Katie A Meyer, Michael F Coleman, Jody Albright, Brian J Bennett, Kari E North, Annie-Green Howard, Penny Gordon-Larsen, Isis Trujillo-Gonzalez, John E French, Stephen D Hursting
{"title":"Sex-specific systemic metabolic predictors of resistance to calorie restriction-induced weight loss in obese Diversity Outbred mice.","authors":"Evan M Paules, Melissa VerHague, Anju A Lulla, Katie A Meyer, Michael F Coleman, Jody Albright, Brian J Bennett, Kari E North, Annie-Green Howard, Penny Gordon-Larsen, Isis Trujillo-Gonzalez, John E French, Stephen D Hursting","doi":"10.1152/ajpregu.00220.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00220.2024","url":null,"abstract":"<p><p>Calorie restriction (CR) is a well-established weight loss strategy, albeit with variation in response. Using genetically heterogeneous mice, we sought to identify metabolic predictors of resistance to CR-induced weight loss. Diversity Outbred mice (150 males, 150 females) were fed a high-fat diet for 12 weeks to generate diet-induced obesity (DIO), then underwent CR for 8 weeks. Body weight and composition, blood glucose, and plasma levels of 9 metabolic hormones were assessed at baseline, following DIO, and following CR. In response to each dietary intervention, the mice displayed substantial heterogeneity across all outcomes, often with sexual dimorphism. Among the metabolic markers, leptin changed the most in response to each dietary intervention. Logistic regression found that resistance to CR-induced weight loss in obese mice was associated with lower glucose levels in males, and with lower levels of insulin, resistin, homeostatic model assessment for insulin resistance (HOMA-IR), and plasminogen activator inhibitor-1, and higher levels of ghrelin in females. Moreover, lower leptin levels predicted resistance to CR-induced weight loss in obese mice, regardless of sex. These preclinical findings provide proof-of-principle that the genetic and phenotypic heterogeneity of DO mice can be leveraged to identify mechanistic predictors that may enhance the personalization of weight loss interventions.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952533","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
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