Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running o...Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.展开更多
Physical activity engagement results in a variety of positive health outcomes,including a reduction in cardiovascular disease risk partially due to eccentric remodeling of the heart.The purpose of this investigation w...Physical activity engagement results in a variety of positive health outcomes,including a reduction in cardiovascular disease risk partially due to eccentric remodeling of the heart.The purpose of this investigation was to determine if four replicate lines of High Runner mice that have been selectively bred for voluntary exercise on wheels have a cardiac phenotype that resembles the outcome of eccentric remodeling.Adult females(average age 55 days)from the 4 High Runner and 4 non-selected control lines were anaesthetized via vaporized isoflurane,then echocardiographic images were collected and analyzed for structural and functional differences.High Runner mice in general had lower ejection fractions compared to control mice lines(2-tailed p=0.0236)and tended to have thicker walls of the anterior portion of the left ventricle(p=0.065).However,a subset of the High Runner individuals,termed mini-muscle mice,had greater ejection fraction(p=0.0006),fractional shortening percentage(p<0.0001),and ventricular mass at dissection(p<0.0027 with body mass as a covariate)compared to non-mini muscle mice.Mice from replicate lines bred for high voluntary exercise did not all have inherent positive cardiac functional or structural characteristics,although a genetically unique subset of mini-muscle individuals did have greater functional cardiac characteristics,which in conjunction with their previously described peripheral aerobic enhancements(e.g.,increased capillarity)would partially account for their increased VO2max.展开更多
Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegener...Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate primary(mainly in the superior retina) from secondary(mainly in the inferior retina) degeneration. Therefore, we compared the survival of retinal ganglion cells between Sprague-Dawley rat runners and non-runners both in the superior and inferior retinas. Excitotoxicity, oxidative stress, and apoptosis are involved in the degeneration of retinal ganglion cells in glaucoma. So we also used western immunoblotting to compare the expression of some proteins involved in apoptosis(phospho-c-Jun N-terminal kinases, p-JNKs), oxidative stress(manganese superoxide dismutase, MnSOD) and excitotoxicity(glutamine synthetase) between runners and non-runners after partial optic nerve transection. Results showed that voluntary running delayed the death of retinal ganglion cells vulnerable to primary degeneration but not those to secondary degeneration. In addition, voluntary running decreased the expression of glutamine synthetase, but not the expression of p-JNKs and MnSOD in the superior retina after partial optic nerve transection. These results illustrated that primary degeneration of retinal ganglion cells might be mainly related with excitotoxicity rather than oxidative stress; and the voluntary running could down-regulate excitotoxicity to delay the primary degeneration of retinal ganglion cells after partial optic nerve transection.展开更多
Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic eff...Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.展开更多
【目的】探讨长期自主跑轮运动对心肌梗死大鼠心肌重塑的影响及可能机制。【方法】雄性Wistar大鼠随机分为心梗安静组(MI-S),心梗运动组(MI-Ex)、假手术安静组(SH-S)和假手术运动组(SH-Ex)。MI-Ex组、SH-Ex组进行为期24周的自主跑轮运动...【目的】探讨长期自主跑轮运动对心肌梗死大鼠心肌重塑的影响及可能机制。【方法】雄性Wistar大鼠随机分为心梗安静组(MI-S),心梗运动组(MI-Ex)、假手术安静组(SH-S)和假手术运动组(SH-Ex)。MI-Ex组、SH-Ex组进行为期24周的自主跑轮运动,MI-S组和SH-S组安静饲养。实验后,心脏超声检测心脏结构与功能,左室导管法测定血流动力学参数,称量体质量(BW)后取心脏并测定心脏指数;Masson染色法进行组织病理学观察并获取胶原容积分数(CVF);实时荧光定量PCR检测心肌心纳素(ANF)、肌质网Ca2+-ATP酶(SERCA2a)、α-肌球蛋白重链(α-MHC)和β-肌球蛋白重链(β-MHC)m RNA表达量。【结果】(1)与SH-S组比较,MI-S组HW、HWI、LVW、LVWI、LVIDd、LVIDs、LVWT、LVEDP和CVF及心肌ANF和β-MHC m RNA水平升高(P<0.05),LVFS、LVEF、LVSP、±dp/dtmax及心肌α-MHC和SERCA2a m RNA水平降低(P<0.05)。(2)与MI-S组比较,MIEx组HW、HWI、LVW、LVWI、LVIDd、LVIDs、LVEDP和CVF显著增加(P<0.05),LVFS、LVEF及心肌α-MHC和SERCA2a m RNA水平降低(P<0.05)。(3)与SH-Ex组比较,MI-Ex组运动距离和运动时间显著性升高(P<0.05),平均跑速无显著性差异(P>0.05)。【结论】过度运动促进心梗后大鼠心肌重塑,其机制与大负荷运动诱导的心肌纤维化和收缩蛋白表达下调有关。展开更多
目的探讨自主运动训练在乳腺癌发生发展中的作用及其机制。方法将携带原发性人乳腺癌基因1(breast cancer gene 1,BRCA-1)突变基因的癌细胞在体外进行培养,用连续14 d自主跑轮运动鼠血清以及静坐鼠血清处理BRCA-1突变肿瘤细胞,并将上述...目的探讨自主运动训练在乳腺癌发生发展中的作用及其机制。方法将携带原发性人乳腺癌基因1(breast cancer gene 1,BRCA-1)突变基因的癌细胞在体外进行培养,用连续14 d自主跑轮运动鼠血清以及静坐鼠血清处理BRCA-1突变肿瘤细胞,并将上述条件血清培养的乳腺癌细胞注射到BALB/c裸鼠皮下,观察经过不同处理后体内外BRCA-1突变乳腺癌细胞及移植瘤的情况。结果在体外,与静坐鼠血清处理组相比,自主运动鼠血清处理后抑制了BRCA-1突变乳腺癌细胞的活力、生长,促进其凋亡,差异具有统计学意义(P<0.05);在体内,自主运动鼠血清培养的BRCA-1突变乳腺癌细胞移植瘤较静坐对照组体积减小、生长缓慢(P<0.05),体内外自主运动组均呈现出增强的Caspase-3活性(P<0.05)。结论自主跑轮运动可能通过增强Caspase3的活性、抑制了BRCA1突变乳腺癌细胞以及其在BALB/c裸鼠皮下异种移植瘤的增殖、促进肿瘤细胞凋亡,从而抑制其体内外的生长。展开更多
The aim of this study was to examine the effects of voluntary wheel-running (WR) on body weight (BW), waist circumference, mesenteric fat mass (MFM), adipocyte size, circulating cytokines/hormones, blood pressure (BP)...The aim of this study was to examine the effects of voluntary wheel-running (WR) on body weight (BW), waist circumference, mesenteric fat mass (MFM), adipocyte size, circulating cytokines/hormones, blood pressure (BP) and exercise endurance capacity in 11-month-old normal rats. Three-week WR with about 0.2 km of daily running distance caused a gradual loss in BW despite an increased intake of food/water. MFM decreased as daily running distance increased. Moreover, there was a positive correlation between MFM and BW, waist circumference or adipocyte size. On the other hand, WR significantly decreased systolic/diastolic BPs, and increased endurance exercise capacity. WR rat sera contained lower concentrations of angiotensin II, aldosterone, vasopressin and endothelin-1 and higher concentration of brain natriuretic peptide compared with sedentary rat sera. Thus, WR-induced reduction in resting BPs may be accomplished by attenuated vasoconstriction, enhanced vasodilatation and reduction in blood volume. In addition, circulating vascular endothelial growth factor and interleukin-6 were higher in WR rats, suggesting angiogenesis, anti-inflammation and insulin-sensitization. These results support a prevalent idea that daily light-exercise is a potential strategy for preventing metabolic syndrome.展开更多
基金sponsored by National Natural Science Foundation of China (81800703 and 81970701)Beijing Nova Program (Z201100006820117 and 20220484181)+7 种基金Beijing Municipal Natural Science Foundation (7184252 and 7214258)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities (BMU2021MX013)Peking University Clinical Scientist Training Program (BMU2023PYJH022)China Endocrine and Metabolism Young Scientific Talent Research Project (2022-N-02-01)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation (G2018030)。
文摘Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.
基金The study was funded by the Department of Kinesiology at Michigan State University and NSF grant IOS-2038528 to T.G.and Natalie Holt.
文摘Physical activity engagement results in a variety of positive health outcomes,including a reduction in cardiovascular disease risk partially due to eccentric remodeling of the heart.The purpose of this investigation was to determine if four replicate lines of High Runner mice that have been selectively bred for voluntary exercise on wheels have a cardiac phenotype that resembles the outcome of eccentric remodeling.Adult females(average age 55 days)from the 4 High Runner and 4 non-selected control lines were anaesthetized via vaporized isoflurane,then echocardiographic images were collected and analyzed for structural and functional differences.High Runner mice in general had lower ejection fractions compared to control mice lines(2-tailed p=0.0236)and tended to have thicker walls of the anterior portion of the left ventricle(p=0.065).However,a subset of the High Runner individuals,termed mini-muscle mice,had greater ejection fraction(p=0.0006),fractional shortening percentage(p<0.0001),and ventricular mass at dissection(p<0.0027 with body mass as a covariate)compared to non-mini muscle mice.Mice from replicate lines bred for high voluntary exercise did not all have inherent positive cardiac functional or structural characteristics,although a genetically unique subset of mini-muscle individuals did have greater functional cardiac characteristics,which in conjunction with their previously described peripheral aerobic enhancements(e.g.,increased capillarity)would partially account for their increased VO2max.
基金supported by the National Natural Science Foundation of China,No.81501091(to HYL)Natural Science Foundation of Guangdong Province of China,No.2015A030310201(to HYL)+4 种基金Medical Scientific Research Foundation of Guangdong Province of China,No.A2015393(to HYL)funds of Leading Talents of Guangdong Province of China,No.2013(to KFS)Programme of Introducing Talents of Discipline to Universities,No.B14036(to KFS)National Basic Research Program of China(973 Program),No.2015CB351800(to KFS)Fundamental Research Funds for the Central Universities,No.21609101(to KFS)
文摘Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate primary(mainly in the superior retina) from secondary(mainly in the inferior retina) degeneration. Therefore, we compared the survival of retinal ganglion cells between Sprague-Dawley rat runners and non-runners both in the superior and inferior retinas. Excitotoxicity, oxidative stress, and apoptosis are involved in the degeneration of retinal ganglion cells in glaucoma. So we also used western immunoblotting to compare the expression of some proteins involved in apoptosis(phospho-c-Jun N-terminal kinases, p-JNKs), oxidative stress(manganese superoxide dismutase, MnSOD) and excitotoxicity(glutamine synthetase) between runners and non-runners after partial optic nerve transection. Results showed that voluntary running delayed the death of retinal ganglion cells vulnerable to primary degeneration but not those to secondary degeneration. In addition, voluntary running decreased the expression of glutamine synthetase, but not the expression of p-JNKs and MnSOD in the superior retina after partial optic nerve transection. These results illustrated that primary degeneration of retinal ganglion cells might be mainly related with excitotoxicity rather than oxidative stress; and the voluntary running could down-regulate excitotoxicity to delay the primary degeneration of retinal ganglion cells after partial optic nerve transection.
基金supported by Hong Kong Health and Medical Research FundLeading Talents of Guangdong(2013)+3 种基金Programme of Introducing Talents of Discipline to Universities(B14036)Project of International,as well as Hong Kong,Macao&Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province,China(2013gjhz0002)grants to Jinan University Guangdong-Hong Kong-Macao Cooperation and Innovation Center for Tissue Regeneration and RepairState Key Laboratory of Pharmaceutical Biotechnology,Hong Kong SAR,China
文摘Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.
基金supported by the Project of Hunan Provincial Social Science Achievement Review Committee (No.XSP20YBC255)the Guangxi Science and Technology Plan Project (No.AD20238035)+1 种基金the Open Project of Guangxi Key Laboratory of Brain and Cognitive Neuroscience (No.GKLBCN-20190105-02)the Guangxi Zhuang Autonomous Region Students’ Innovation and Entrepreneurship Training Program of China (No.202010601050)。
文摘【目的】探讨长期自主跑轮运动对心肌梗死大鼠心肌重塑的影响及可能机制。【方法】雄性Wistar大鼠随机分为心梗安静组(MI-S),心梗运动组(MI-Ex)、假手术安静组(SH-S)和假手术运动组(SH-Ex)。MI-Ex组、SH-Ex组进行为期24周的自主跑轮运动,MI-S组和SH-S组安静饲养。实验后,心脏超声检测心脏结构与功能,左室导管法测定血流动力学参数,称量体质量(BW)后取心脏并测定心脏指数;Masson染色法进行组织病理学观察并获取胶原容积分数(CVF);实时荧光定量PCR检测心肌心纳素(ANF)、肌质网Ca2+-ATP酶(SERCA2a)、α-肌球蛋白重链(α-MHC)和β-肌球蛋白重链(β-MHC)m RNA表达量。【结果】(1)与SH-S组比较,MI-S组HW、HWI、LVW、LVWI、LVIDd、LVIDs、LVWT、LVEDP和CVF及心肌ANF和β-MHC m RNA水平升高(P<0.05),LVFS、LVEF、LVSP、±dp/dtmax及心肌α-MHC和SERCA2a m RNA水平降低(P<0.05)。(2)与MI-S组比较,MIEx组HW、HWI、LVW、LVWI、LVIDd、LVIDs、LVEDP和CVF显著增加(P<0.05),LVFS、LVEF及心肌α-MHC和SERCA2a m RNA水平降低(P<0.05)。(3)与SH-Ex组比较,MI-Ex组运动距离和运动时间显著性升高(P<0.05),平均跑速无显著性差异(P>0.05)。【结论】过度运动促进心梗后大鼠心肌重塑,其机制与大负荷运动诱导的心肌纤维化和收缩蛋白表达下调有关。
基金supported by the National Natural Science Foundation of China(No.31270027 and 31270034)Science and Technology Commission of Shanghai MunicipalityChina(No.12JC1401000)
文摘目的探讨自主运动训练在乳腺癌发生发展中的作用及其机制。方法将携带原发性人乳腺癌基因1(breast cancer gene 1,BRCA-1)突变基因的癌细胞在体外进行培养,用连续14 d自主跑轮运动鼠血清以及静坐鼠血清处理BRCA-1突变肿瘤细胞,并将上述条件血清培养的乳腺癌细胞注射到BALB/c裸鼠皮下,观察经过不同处理后体内外BRCA-1突变乳腺癌细胞及移植瘤的情况。结果在体外,与静坐鼠血清处理组相比,自主运动鼠血清处理后抑制了BRCA-1突变乳腺癌细胞的活力、生长,促进其凋亡,差异具有统计学意义(P<0.05);在体内,自主运动鼠血清培养的BRCA-1突变乳腺癌细胞移植瘤较静坐对照组体积减小、生长缓慢(P<0.05),体内外自主运动组均呈现出增强的Caspase-3活性(P<0.05)。结论自主跑轮运动可能通过增强Caspase3的活性、抑制了BRCA1突变乳腺癌细胞以及其在BALB/c裸鼠皮下异种移植瘤的增殖、促进肿瘤细胞凋亡,从而抑制其体内外的生长。
文摘The aim of this study was to examine the effects of voluntary wheel-running (WR) on body weight (BW), waist circumference, mesenteric fat mass (MFM), adipocyte size, circulating cytokines/hormones, blood pressure (BP) and exercise endurance capacity in 11-month-old normal rats. Three-week WR with about 0.2 km of daily running distance caused a gradual loss in BW despite an increased intake of food/water. MFM decreased as daily running distance increased. Moreover, there was a positive correlation between MFM and BW, waist circumference or adipocyte size. On the other hand, WR significantly decreased systolic/diastolic BPs, and increased endurance exercise capacity. WR rat sera contained lower concentrations of angiotensin II, aldosterone, vasopressin and endothelin-1 and higher concentration of brain natriuretic peptide compared with sedentary rat sera. Thus, WR-induced reduction in resting BPs may be accomplished by attenuated vasoconstriction, enhanced vasodilatation and reduction in blood volume. In addition, circulating vascular endothelial growth factor and interleukin-6 were higher in WR rats, suggesting angiogenesis, anti-inflammation and insulin-sensitization. These results support a prevalent idea that daily light-exercise is a potential strategy for preventing metabolic syndrome.
