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The journey towards physiology and pathology: Tracing the path of neuregulin 4

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Genes & Diseases 2024年第2期11卷 687-700页

作者： Min Chen Jieying Zhu Hongyang Luo Wangjing Mu Liang Guo school of exercise and Health and Shanghai Frontiers science Research Base of exercise and Metabolic Health Shanghai University of SportShanghai 200438China

Neuregulin 4 (Nrg4),an epidermal growth factor (EGF) family member,can bind to and activate the ErbB4 receptor tyrosine ***4 has five different isoforms by alternative splicing and performs a wide variety of ***4 is involved in a spectrum of physiological processes including neurobiogenesis,lipid metabolism,glucose metabolism,thermogenesis,and *** pathological processes,Nrg4 inhibits inflammatory factor levels and suppresses apoptosis in inflammatory *** addition,Nrg4 could ameliorate obesity,insulin resistance,and cardiovascular ***,Nrg4 improves non-alcoholic fatty liver disease (NAFLD) by promoting autophagy,improving lipid metabolism,and inhibiting cell death of ***,Nrg4 is closely related to the development of cancer,hyperthyroidism,and some other ***,elucidation of the functional role and mechanisms of Nrg4 will provide a clearer view of the therapeutic potential and possible risks of Nrg4.

关键词： Angiogenesis Cardiovascular diseases Inflammation Insulin resistance Lipid and glucose metabolism NAFLD Neurobiogenesis Obesity

Diet restriction and exercise alleviate cognitive reduction of high fat diet(HFD)-induced obese mice by rescuing inflammation-mediated compromised insulin signaling pathway through activating AMPK/SIRT1 signal pathway and suppressing TLR4 signal pathway

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Food science and Human Wellness 2024年

作者： Hu Zhang Ye Zhang Jiling Liang Jiahang Li Miao He Xin Liu Jielun Huang Minghui Wang Jingjing Fan Ning Chen Tianjiu Research and Development Center for exercise Nutrition and Foods， Hubei Key Laboratory of exercise Training and Monitoring， College of sports Medicine， Wuhan sports University Physical Education Institute， Hubei University of science and Technology

Obesity， caused by excessive energy， leads to body weight gain and various diseases， including cognitive impairment. Current studies suggest that diet restriction such as optimal fasting and regular exercise are crucial for improving cognitive capacity. However， further exploration is needed to understand the specific mechanisms of high fat diet (HFD)-induced cognitive decline in obesity. In the present study， 4-month-old mice were subjected to HFD feeding for 18 weeks， followed by aerobic exercise and high-intensity intermittent exercise， regular diet feeding， and intermittent fasting for 8 weeks， and then used to evaluate cognitive capacity， inflammation， compromised insulin signaling pathway， oxidative stress， and apoptosis in hippocampal tissue， as well as AMPK/SIRT1 and TLR4 signal pathways. Obese mice revealed impaired cognitive capacity as compared with mice fed with regular diets. In contrast， aerobic exercise， high-intensity intermittent exercise， regular diet， and intermittent fasting could inhibit apoptosis caused by inflammation-mediated compromised insulin signaling pathway in hippocampal tissues through activating the AMPK/SIRT1 signal pathway and suppressing the TLR4 signal pathway， thereby rescuing the cognitive impairment of obese mice. Therefore， diet restriction and exercise interventions may play a positive role in reverting obesity-induced cognitive impairment.

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Aerobic exercise mitigates high-fat diet-induced cognitive decline through suppressing liver-brain-axis-mediated ATF3 and neuroinflammation

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Food science and Human Wellness 2024年

作者： Tong Wu Baoxuan Lin Min Jia Jinxiu Li Ning Chen Tianjiu Research and Development Center for exercise Nutrition and Foods， Hubei Key Laboratory of exercise Training and Monitoring， College of sports Medicine， Wuhan sports University

It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function. The concept of multi-organ crosstalk coordinating disease progression has become the current research hot topic. However， there remains an urgent need to elucidate its specific mechanisms. This study aimed to explore the impact of a high-fat diet （HFD） on liver health and cognitive function， and to further uncover the regulatory effect of aerobic exercise by liver-specific ATF3 knockout (ATF3cKO) mice in a “liver-brain” axis mode. The 5-week-old C57BL/6 and ATF3cKOmice were fed with HFD for 32 weeks， and sequentially subjected to aerobic exercise intervention at the 20thweek for another 12 consecutive weeks. Meanwhile， C57BL/6 mice were provided with a normal diet as the control group. The functional parameters of liver and brain of all mice were assessed. Cognitive capacity of all mice was assessed by the Morris water maze （MWM）. Inflammatory factors in the serum and brain of mice were quantified using enzyme-linked immunosorbent assay （ELISA）， and the expression of inflammasomes was detected by immunohistochemistry （IHC）. Additionally， the activation of NF-κB and PI3K signal pathways was analyzed by Western blotting. In this study， HFD impaired hepatic and brain functions， while aerobic exercise and liver-specific ATF3 knockout suppressed inflammatory factors in the peripheral circulation through hepatoprotective mechanisms， thereby attenuating cerebral inflammation and preserving neurological integrity， as well as mitigating HFD-induced cognitive decline.

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Molecular insights of exercise therapy in disease prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2564-2597页

作者： David Walzik Tiffany Y.Wences Chirino Philipp Zimmer Niklas Joisten Division of Performance and Health(sports Medicine) Institute for Sport and Sport ScienceTU Dortmund University44227 DortmundNorth Rhine-WestphaliaGermany Division of exercise and Movement science Institute for Sport ScienceUniversity of Göttingen37075 GöttingenLower SaxonyGermany

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases,the underlying biological mechanisms have not been fully *** exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle,cardiac muscle,adipose,and liver *** signaling molecules,which are collectively termed exerkines,form a heterogenous group of bioactive substances,mediating inter-organ crosstalk as well as structural and functional tissue *** scientific endeavors have focused on identifying and characterizing new biological mediators with such ***,some investigations have focused on the molecular targets of exerkines and the cellular signaling cascades that trigger adaption processes.A detailed understanding of the tissue-specific downstream effects of exerkines is crucial to harness the health-related benefits mediated by exercise and improve targeted exercise programs in health and ***,we review the current in vivo evidence on exerkine-induced signal transduction across multiple target tissues and highlight the preventive and therapeutic value of exerkine signaling in various *** emphasizing different aspects of exerkine research,we provide a comprehensive overview of(i)the molecular underpinnings of exerkine secretion,(ii)the receptor-dependent and receptor-independent signaling cascades mediating tissue adaption,and(iii)the clinical implications of these mechanisms in disease prevention and treatment.

关键词： prevention treatment collective

L-theanine/α-Ketoglutarate/Nrf2 axis promotes exercise-mediated amelioration of NASH in mice

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Food science and Human Wellness 2024年

作者： Wang-Jing Mu Min Chen Jie-Ying Zhu Hong-Yang Luo Yang Li Shan Li Lin-jing Yan Ruo-ying Li Liang Guo school of exercise and Health and Collaborative Innovation Center for sports and Public Health， Shanghai University of Sport Shanghai Frontiers science Research Base of exercise and Metabolic Health， Shanghai University of Sport Key Laboratory of exercise and Health sciences of the Ministry of Education， Shanghai University of Sport

L-Theanine (LTA) is a non-protein amino acid mainly found in tea plants with many beneficial effects. exercise exerts a wide range of benefits in metabolic health. Here， we show that exercise or gastric lavage intervention on mice with LTA improves diet-induced NASH in mice. Meanwhile， combinatory therapy shows that exercise and LTA synergistically improve obesity-related metabolic disorders and NASH phenotypes， including hepatic steatosis， inflammation， cell death and oxidative stress. In vivo studies indicate that LTA inhibits free fatty acid (FFA)-induced hepatocyte injury， including steatosis， oxidative stress and apoptosis. Knockdown of Nrf2 blunts the role of LTA in inhibiting FFA-induced hepatocyte oxidative stress and dysfunction. Mechanistically， LTA increases the α-ketoglutarate (α-KG) level in hepatocytes， which increases the transcription of Nrf2 by inducing active DNA demethylation on its promoter. Moreover， LTA promote the above α-KG/Nrf2 axis in synergy with exercise， thereby more efficiently inhibiting hepatic oxidative stress and ameliorating diet-induced NASH in mice. Our results suggest that， through promoting the α-KG/Nrf2 axis-mediated anti-oxidative pathway， the combination of LTA and exercise may provide an effective measure for the prevention and control of NASH.

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Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity

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World Journal of Diabetes 2024年第7期15卷 1589-1602页

作者： Wei Luo Yue Zhou Li-Ying Wang Lei Ai Department of sports and Health sciences Nanjing Sport InstituteNanjing 210014Jiangsu ProvinceChina Department of exercise Physiology Beijing Sport UniversityBeijing 100084China Department of sports Physiology Research Jiangsu Research Institute of Sports ScienceNanjing 210033Jiangsu ProvinceChina

BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal ***,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to *** exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is *** To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal *** We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical ***,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG *** effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent *** mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG *** The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P0.8).Compered to M group,myotube area,myotube n

关键词： Macrophages phenotype Myoblasts Cross-talk Glucose toxicity Chronic inflammation Insulin sensitivity

Commentary on "Association of daily sitting time and leisure-time physical activity with body fat among ***"

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Journal of Sport and Health science 2024年第2期13卷 127-129页

作者： Barbara E.Ainsworth school of exercise and Health Shanghai University of SportShanghai 200438China

In their study,association of daily sitting time and leisure-time physical activity (LTPA) with body fat among ***,Liao et al.^(1) analyzed data from the 2011-2018 National Health and Examination Survey to examine associations between h/day sitting,meeting (or not meeting) the *** Activity Guidelines of≥150 min/week of moderate-and vigorous-intensity LTPA,and combinations of sitting time and LTPA on totaland trunk percent body fat (BF%).

关键词： U.S. adult among

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Journal of Sport and Health science 2024年第5期13卷 672-673页

作者： Barbara E.Ainsworth Zeyun Feng school of exercise and Health Shanghai University of SportShanghai 200438China

In Volume 13,Issue 1,of the Journal of Sport and Health science,Herold et al.1 present a systematic review and classification of digital and home-based physical training interventions aiming to support healthy cognitive *** interventions were reviewed:digital databases(i.e.,YouTube videos and apps),online classes,and technology-based exercise devices(e.g.,exergames).

关键词： cognitive games aging

Impact of exercise on markers of B cell-related immunity:A systematic review

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Journal of Sport and Health science 2024年第3期13卷 339-352,I0002页

作者： David Walzik Sergen Belen Karen Wilisch Marie Kupjetz Silvana Kirschke Tobias Esser Niklas Joisten Alexander Schenk Sebastian Proschinger Philipp Zimmer Division of Performance and Health(sports Medicine) Institute for Sport and Sport ScienceTU Dortmund UniversityDortmund 44227Germany

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific *** alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are *** systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human ***:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of science,and Embase were searched on March 8,***-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were *** and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in *** characteristics,outcome measures,and statistically significant changes were summarized ***:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise *** included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control *** and plasma immunoglobulin A levels were most consistently increased in response to exercise ***:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise ***-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

关键词： Antibody B-lymphocyte exercise Humoral immunity Immune system