운동에 의한 CAMTA1의 발현 감소가 간세포의 지방산화에 미치는 영향

문효열,박성태,김기정 한국운동생리학회(구 한국운동과학회) 2013 운동과학 Vol.22 No.1

운동이 비만이나 비알콜성 지방간과 같은 대사 질환에 미치는 효과는 잘 알려져 있지만, 그 기작에 대한 연구는 미흡한 실정이다. 마이크로RNA는 생명체의 생물학적 기능 수행에 필수적이며 최근 약물의 표적으로도 알려져 있다. 이번 실험에서는 운동 후 나타나는 간의 지방 산화에 영향을 미치는 새로운 표적 유전자 CAMTA1을 생물 정보학적 분석을 통해 찾았다. CAMTA1의 발현을 줄였을 경우 인간 간 세포에서 체내 에너지 센서인 AMPK를 활성화 시키는 것과 지방 대사에 중요한 전사인자인 PGC-1a 와 CPT1의 발현이 증가됨을 확인하였다. 또한 같은 조건에서 CAMKK-b 그리고 AMPK pathway를 거쳐 지방 산화가 증가해 있는 것을 각각의 저해제 처리한 연구를 통해 알 수 있었다. 일련의 실험을 통해 운동에 의한 지방산화에 있어서 CAMTA1의 발현 감소가 역할을 할 수 있으며, 이러한 현상은 CAMKK-b 그리고 AMPK pathway을 통해 매개 수 있다는 사실을 처음으로 밝혔다. 후속연구가 필요하지만, 이 결과들은 운동 후 발현이 감소된 CAMTA1이 운동의 생체지표로 사용될 수 있으며 더 나아가 운동에 지방 대사 효과에 중요한 역할을 할 수 있다는 것을 제시해주고 있다. Exercise is known to have an ameliorating effect on chronic metabolic diseases such as obesity, diabetes and nonalcoholic fatty liver disease(NAFLD), yet the underlying mechanism is not fully understood. To identify the reduced expression of genes by exercise and to characterize the role of this gene in lipid metabolism, we first identified the one of candidate gene, Calmodulin-binding transcription activator 1 (CAMTA 1) which showed reduced- mRNA expression after exercise from GEO datasets. Then we confirmed the expression of this candidate gene, CAMTA1, was decreased by 4 week treadmill experiment. Transfection of CAMTA1 siRNA increased phosphorylation of AMPK and ACC in the HepG2, human hepatoblastoma cell line. This was accompanied by increases of palmitate oxidation in CAMTA1 siRNA transfected cell lines compared to their control cells. Furthermore, AMPK and CaMKK _ pathway mediate the knockdown of CAMTA1-induced palmitate oxidation. Taken together, these results suggest a novel role of CAMTA1 in mediating the lipid oxidation of exercise, probably via AMPK pathway.

Physical Activity and Brain Plasticity

문효열,Henriette van Praag 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.4

Recent research suggests that the brain has capable of remarkable plasticity and physical activity can enhance it. In this editorial letter, we summarize the role of hippocampal plasticity in brain functions. Furthermore, we briefly sketched the factors and mechanisms of motion that influence brain plasticity. We conclude that physical activity can be an encouraging intervention for brain restoration through neuronal plasticity. At the same time, we suggest that a mechanistic understanding of the beneficial effects of exercise should be accompanied in future studies.

The effect of voluntary exercise on light cycle stress-induced metabolic resistance

문효열,정인철 한국운동영양학회 2023 Physical Activity and Nutrition (Phys Act Nutr) Vol.27 No.3

[Purpose] Disruption of circadian genes affects metabolic homeostasis. Regular exercise programs prevent metabolic dysfunction and alter circadian gene expression In this study, we investigated whether exercise affects light stress-induced circadian rhythm derangement and metabolic resistance. [Methods] A circadian rhythm derangement mouse model was designed by extending the light exposure by two hours (14 L/10 D) for three weeks. Nine-week-old male mice were single-caged and divided into four groups: sedentary groups with or without light stress, and voluntary wheel-trained groups with or without light stress. In addition, differentiated myotubes were cultured in the presence of dexamethasone with or without 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR). The comprehensive laboratory animal monitoring system was used to analyze the metabolic changes in mice. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the mRNA expression levels of circadian genes in animal and cell culture models. [Results] Three weeks of light stress reduced the running distance and increased the weight of mice. In addition, VO2 consumption and heat production were increased during the night cycle under non-stress conditions but not under stress conditions. PCR analysis revealed that exercise and stress altered the expression levels of circadian genes in the hypothalamus and quadriceps muscles. mRNA expression levels of period circadian regulator 1 were downregulated in the quadriceps muscles of the stressed sedentary group compared to that in muscles of the non-stressed sedentary group. Furthermore, differentiated myotube cells cultured in the presence of dexamethasone, with or without AICAR, showed distinct oscillation patterns at various time points. [Conclusion] Our study demonstrates that exercise partially prevents metabolic disruption by regulating the circadian gene expression in skeletal muscles.

포스트코로나 시대의 심폐운동검사 프로토콜 제언

손정민,이민철,문효열 중앙대학교 학교체육연구소 2023 Asian Journal of Physical Education of Sport Scien Vol.11 No.2

The purpose of this study was to explain the necessity of applying cardiopulmonary exercise testing(CPET) in the Post-COVID condition and compare several traditional protocols applied in Post-COVID sequelae. According to recent studies, Post-COVID condition show a decrease in CPET, and that is recommended to evaluate symptoms. However, there is no study on which protocol is appropriate to apply when testing when CPET is performed in Post-COVID condition. This systematic review examines the effectiveness of COVID-19, COVID-19 sequelae, Post-COVID condition, and CPET. Pubmed, EMBASE, Google Scholar, KISS, RISS, and JKMS databases were used to search for all studies, and assessments from December 2019 to 2022. As a result, most precedent studies have used modified Bruce and/or Ramp protocols for CPET in Post-COVID condition. High-intensity protocol is inappropriate to apply in Post-COVID condition on account of the large initial workload since it is developed to evaluate athletes’ cardiopulmonary fitness. This study suggests that a new protocol develops more suitable for Post-COVID condition. 본 연구는 포스트코로나 시대의 심폐운동검사 적용의 필요성과 코로나 후유증 대상자에게 적용되는 여러 심폐운동검사 프로토콜의 비교에 대한 연구이다. 최근 연구에 따르면 코로나 후유증을 가진 대상자들은 심폐체력의 저하가 나타나며 증상에 대한 평가를 위해서 심폐운동검사가 권장된다. 그러나 코로나 후유증 대상자에게 심폐운동검사를 시행할 때 어떠한 프로토콜을 적용하는 것이 적합한가에 대한 연구는 이루어지고 있지 않다. PubMED, EMBASE, Google Scholar, KISS, RISS, JKMS를 사용하여 코로나19 발생 시기인 2019년 12월부터 2022년 12월까지의 기간으로 설정하여 COVID-19, COVID-19 sequelae, Post-COVID condition, Cardiopulmonary exercise testing(CPET) 검색어를 사용하여 문헌을 검색하였다. 그 결과, 심폐운동검사를 적용한 여러 선행연구는 기존의 Modified Bruce 프로토콜, Ramp 프로토콜 등의 검사 프로토콜을 적용하였다. 고강도 프로토콜들은 최초부하가 높고 단계별 강도 증가가 높아 코로나 후유증 대상자에게 적용하는 것은 부적합하다. 따라서 본 연구를 통해 기존 프로토콜을 토대로 코로나 후유증 대상자에게 더욱 적합한 새로운 프로토콜의 개발이 필요하다고 사료된다.

학생 건강 체력평가시스템(PAPS)을 이용한 고등학생의 체력측정요소 간의 관계분석

박재범,안주은,문효열,김유겸,엄혜성 경북대학교 사범대학부속중등교육연구소 2017 중등교육연구 Vol.65 No.4

청소년의 건강과 체력을 다면적으로 정량화하여 적합한 체육교육과 연계하기 위한 노력은 중등교육에 있어서 필수적인 요소이다. 본 연구에서는 최근 운영이 확대되고 있는 학생건강체력 평가제(PAPS)가 본래의 취지에 부합하여 다양한 건강체력의 요소들을 독립적으로 평가하고 있는지 검토하였다. PAPS를 통해 총 798명(남:399, 여:399) 고등학교 학생들의 건강체력 및 체질량 지수(BMI)를 남녀 그리고 학년별로 분석하여 건강체력 요소들 간의 관계를 조사하였으며 특히 기존 체력장과 비교하여 PAPS에서 새로이 추가된 BMI와 건강체력 요소의 상관관계를 분석하였다. 그 결과 남학생의 경우는 심폐지구력과 순발력이 독립적으로 평가되고 있는 지에 대한 재고가 필요한 것으로 판단된다. 또한 정상보다 높은 BMI 수치가 운동능력에 부정적 영향을 미치는 경향은 여학생에 한해서만 관찰되었으며 이는 남학생의 비만도가 여학생에 비하여 상대적으로 과대평가되었을 가능성을 시사한다. PAPS가 정확한 신체조성 평가를 기반으로 적합한 신체활동 교육을 제시하기 위해서는 남학생의 비만도를 더 합리적으로 판단할 기준 마련이 필요한 것으로 판단된다.

마이크로어레이 분석을 통한 일회성 유산소 운동이 마우스 비복근의 초기 에너지 대사관련 유전자에 미치는 영향

이지현,장적적,곽성은,신형은,문효열,송욱 한국운동생리학회 2019 운동과학 Vol.28 No.1

PURPOSE: The purpose of this study was to examine the infancy changes of metabolic gene expression level in mouse gastrocnemius muscle after after 1 hour acute treadmill exercise. METHODS: C57BL/6 mouse were randomly divided into control (n=5) and 1 hour acute treadmill exercise intervention group (n=5). After the intervention, we extracted total mRNA from the mouse gastrocnemius following the whole set of genes were analyzed by microarray using Affymetrix GeneChip Clariom_S_Mouse Array. The significantly meaningful differentially expressed genes (DEGs) were extracted and compared with the bioinformatic tools. Further analysis of DEGs were conducted using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology database. Significant cut-off by Fold change and LPE test were used as statistical test. RESULTS: Fifty six upregulated and 65 downregulated DEGs were identified after the 1 hour of treadmill exercise. Nr4a3, Nr4a2, Btg2, Otud1, Sik1, Thbs1, Irs2 were included in the top 10 upregulated genes and Ube2l6, Scd3 were one of the most downregulated genes in the DEGs. In gene ontology analysis, metabolic process (>70 counts), organic substance metabolic process (>70) and cellular metabolic process (>60) were in the top 10 terms in the category of biological process. In the molecular function category, binding and protein binding term had more than 80s and 60s count genes each and they were statistically significant (p≤.001) with located on first and second place. In KEGG pathway enrichment analysis, many DEGs were related to MAPK signaling pathway, AMPK signaling pathway, Metabolic pathway, Protein processing in endoplasmic reticulum and Glycolysis/gluconeogenesis pathway. Also, several DEGs (HK1, HK2, Adh1 etc.) related to metabolism were statistically significant. CONCLUSIONS: One hour acute treadmill exercise could sufficiently change some energy metabolism and adaptation related genes in mouse gastrocnemius muscle. In this microarray analysis, Nr4a3, Nr4a2, Btg2, Otud1, Sik1, Thbs1, Irs2, Ube2l6, and Scd3 were newly categorized as DEGs in respect of energy metabolism.

Potential involvement of neutrophils on exercise effects in breast cancer malignancy

고강은,우송원,채영찬,이민철,문효열 한국운동영양학회 2023 Physical Activity and Nutrition (Phys Act Nutr) Vol.27 No.4

[Purpose] This review aimed to comprehensively explore and elucidate multifaceted neutrophils in breast cancer, particularly in the context of physical activity. Neutrophils play a critical role in the tumor microenvironment and systemic immune response, despite their short half-life and terminal differentiation. Through a thorough review of research related to changes in immunity in breast cancer during exercise, this review aims to provide comprehensive insights into immunological changes, especially focusing on neutrophils. Recognizing that much of the existing research has predominantly focused on T cells and nature killer (NK) cells, our review seeks to shift the spotlight toward understanding how exercise affects neutrophils, a less-explored but critical immune response component in breast cancer. [Methods] This study involved an extensive review of the literature (from 2000 to 2023) using the PubMed, Science Direct, and Google Scholar databases. The keywords chosen for the searches were “immune cells and exercise,” “exercise and breast cancer,” “tumor microenvironment and neutrophils,” and “neutrophils and exercise and breast cancers.” [Results] Neutrophils in the tumor microenvironment can exhibit distinct phenotypes and functions. These differences have yielded conflicting results regarding tumor progression. Exercise plays a positive role in breast cancer and alters the immune system. Physical activity can quantitatively and functionally regulate neutrophils under various conditions such as metabolic disruption or senescence. [Conclusion] This short communication outlines exercise-induced neutrophil diversification and its role in breast cancer progression, both within and systemically within the tumor microenvironment. Exercise may provide benefits through the potential neutrophil involvement in breast cancer.

Potential role of exercise-induced glucose-6-phosphate isomerase in skeletal muscle function

곽성은,신형은,Didi Zhang,이지현,윤경진,배준현,문효열,송욱 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.2

[Purpose] Recent studies have shown that glucose-6-phosphate isomerase (GPI)—which is a glycolysis interconversion enzyme—reduces oxidative stress. However, these studies are limited to tumors such as fibrosarcoma, and there are no studies that have examined the effects of exercise on GPI expression in mice skeletal muscle. Furthermore, GPI acts in an autocrine manner thorough its receptor, autocrine motility factor receptor (AMFR); therefore, we investigated expression level changes of secreted GPI from skeletal muscle in in vitro study to examine the potential role of GPI on skeletal muscle. [Methods] First, we performed an in vitro study, to identify the condition that upregulates GPI levels in skeletal muscle cells; we treated C2C12 muscle cells with an exercise-mimicking chemical, AICAR. AICAR treatment upregulated GPI expression level in C2C12 cell and its secretomes. To confirm the direct effect of GPI on skeletal muscle cells, we treated C2C12 cells with GPI recombinant protein. [Results] We found that GPI improved the viability of C2C12 cells. In the in vivo study, the exercise-treated mice group showed upregulated GPI expression in skeletal muscle. Based on the in vitro study results, we speculated that expression level of GPI in skeletal muscle might be associated with muscle function. We analyzed the association between GPI expression level and the grip strength of the all mice group. The mice group’s grip strengths were upregulated after 2 weeks of treadmill exercise, and GPI expression level positively correlated with the grip strength. [Conclusion] These results suggested that the exercise-induced GPI expression in skeletal muscle might have a positive effect on skeletal muscle function.

Effects of Exercise on Physical Fitness and Strength According to the Frailty Level of Female Elderly with Hypertension

백경완,이민철,전태봉,유준일,박진성,문효열,김지석 한국운동생리학회 2020 운동과학 Vol.29 No.4

PURPOSE: The purpose of this study was to determine the effects of exercise on physical fitness and strength according to their frailty level of the hypertensive female elderly aged over 65. METHODS: Female elderly subjects (>65 year) with hypertension (n=90) were classified according to their level of frailty (Fr_), and were divided into control group (Ctrl) and exercise group (Ex). Hypertensive female elderly in exercise groups were subjected to 8-week combined exercise of aerobic (stretching and walking) and resistance (elastic band and weight training) exercise twice per week (50 minutes×2 times×8 weeks). Body composition, functional fitness and skeletal muscle strength were evaluated as main variables (Ctrl, n=27; Ex, n=23; Fr_Ctrl, n=17; Fr_Ex, n=23). RESULTS: Body composition, blood pressure, fasting glucose level (include hemoglobin A1c) and blood lipid profile did not interact with the exercise intervention and frailty level. Records of 30-second chair stretch test, two-minute walk test and arm curl increased after exercise intervention regardless of frailty level. The strength of quadriceps femoris increased after exercise intervention regardless of the level of frailty. However, the strength of biceps femoris (p<.001), biceps brachii (p<.05) and triceps brachii (p<.001) was significantly increased in the Fr_Ex compared to pre-intervention of exercise. CONCLUSIONS: The classification according to the level of frailty in hypertensive female elderly can have a significant effect on the degree of muscle strength improvement by exercise intervention. In addition, this study newly discovered that the improvement of 30-s chair stretch test record in the hypertensive elderly women appeared faster than the improvement of the rapid-gait test record independently of the level of frailty.

10주 트레드밀 운동이 비만 쥐 혈관 내피세포의 오토파지 조절장애 개선에 미치는 효과

김지석,전태봉,백경완,유준일,안상현,문효열 한국운동생리학회 2019 운동과학 Vol.28 No.3

is an important contributor to the pathogenesis of atherosclerosis. The purpose of this study was to determine whether regular aerobic exercise can improve obesity-induced dysregulation of autophagy in mice arterial endothelial cells. METHODS: High-fat diet-induced obese mice were subjected to the treadmill running for 10 weeks (15 m/min, 1 hour/day, 6 days/ week). Endothelial cells were isolated from aorta by perfusing with QIAzol reagent. The mRNA and protein expressions of autophagyrelated genes were investigated by qRT-PCR and western-blot respectively. Statistical analysis was performed by one-way ANOVA. RESULTS: Autophagy-related gene expressions in both levels of mRNA and protein were significantly decreased in vascular endothelial cells and arterial vessels of obese mice. However, these phenomena have been partly reversed by the regular treatment of treadmill exercise for 10 weeks. Furthermore, eNOS downregulation induced by the obesity was also improved by the regular aerobic exercise, representing enhanced endothelial function. CONCLUSIONS: The current study has shown that the obesity-induced autophagy dysregulation and vascular dysfunction can be partly improved by the regular aerobic exercise in mice vascular endothelial cells.