Original Study : The Role of Phospholipase C Beta in Fatty Acid Induced AMPK Signaling during Exercise

( Hyo Youl Moon ) 한국운동생리학회(구 한국운동과학회) 2014 운동과학 Vol.23 No.3

문효열. 운동에 의한 Phospholipase C beta의 발현이 근육세포 내 에너지 대사관련 유전자 조절에 미치는 영향. 운동과학, 제23권 3호, 249-256, 2014. 운동 중 근육은 필요한 에너지를 충족시키기 위해 대사에 관련된 유전자 발현이나 효소의 활성화 조절을 통해 환경에 적응한다. 포스포라이페이즈 C는 근육 세포의 성장, 분화, 대사에 중요하다고 알려져 있지만, 운동에 의한 변화와 그 역할에 대해서는 알려진 바가 없다. 이번 실험을 통해 여러 isotype 중에서 포스포라이페이즈 C beta2의 유전자 양과 단백질 양이 4주간의 트레이드밀 운동을 한 그룹의 가자미근에서 증가해 있는 것을 확인하였다. 또한 포스포라이페이즈 C beta2와 결합하여 작용하는 것으로 알려진 G 단백질 수용체의 발현을 조사한 결과 lipid receptor인 FAR이 운동 후 함께 증가하고 있음을 중합효소 연쇄반응을 통해 발견하였다. FAR을 수용체로 사용하고 있는 oleic acid를 근육세포에 처리한 결과 세포내 에너지 조절자 역할을 하는 AMPK의 활성이 증가하는 것을 확인하였다. AMPK의 타겟 유전자인 PPARgamma와 PGC1이 oleic acid 처리에 의해 증가되었고, 이러한 결과가 포스포라이페이즈 C에 의해 매개된다는 것을 PLC inhibitor 전처리 실험을 통해 알 수 있었다. 이러한 결과는 장기간 운동에 필요한 에너지원인 지방산이 포스포라이페이즈 C에 의해 운동 중 근육의 에너지 대사측면의 적응과정에 기여하고 있음을 보여주고 있다. 포스포라이페이즈 C의 특이적인 결핍이 있는 실험동물 및 임상 실험의 전제하에 세계적으로 꾸준히 증가하고 있는 비만이나 당뇨 등의 환자 처방에 PLC가 새로운 타겟이 될 것으로 제시된다. 후속연구가 필요하지만, 이 결과들은 운동 후 발현에 변화가 있는 포스포라이페이즈 C의 서브 타입들이 운동의 생체지표로 사용될 수 있으며 더 나아가 운동의 지방 대사 효과에 중요한 역할을 할 수 있다는 것을 제시해주고 있다. Moon, Hyo-Youl. The Role of Phospholipase C Beta in Fatty Acid Induced AMPK Signaling During Exercise. Exercise Science, 23(3): 249-256, 2014. Chronic exercise triggers muscle adaptation in response to energy demand by switching muscle types, increasing mitochondria contents, or changing gene expression patterns. Phospholipase C (PLC) is known to be involved in the metabolism, proliferation, and differentiation of muscle cells. However, its function during exercise has not been studied. In this study, 19 mice were divided into 2 groups, exercise and control groups. The mice in the exercise group were exercised on a treadmill for 4 weeks. We observed that both mRNA and protein expression levels of PLCβ2 increased in the skeletal muscles, particularly in the soleus muscle, of mice after 4 weeks of treadmill exercise. The expression of GPR40, a G-protein coupled receptor (GPCR) and a putative binding partner of PLCβ2, was also found to be increased in the mice belonging to the exercise group. To investigate the role of GPR40 in muscle adaptation, the mice were administered oleic acid, which activates AMPK and acetyl-CoA carboxylase (ACC). The results revealed that AMPK-target genes such as Cebp-β and Ppar-γ were upregulated upon oleic acid treatment. Furthermore, pre-treatment with STO-609, a PLC inhibitor, downregulated the expression of AMPK-target genes in differentiated muscle cell lines. Taken together, these results suggest a novel role for PLCβ2, that involves the regulation of fatty acid metabolism during exercise.

Involvement of exercise-induced macrophage migration inhibitory factor in the prevention of fatty liver disease

Moon, Hyo Youl,Song, Parkyong,Choi, Cheol Soo,Ryu, Sung Ho,Suh, Pann-Ghill BioScientifica 2013 The Journal of endocrinology Vol.218 No.3

<P>Physical inactivity can lead to obesity and fat accumulation in various tissues. Critical complications of obesity include type II diabetes and nonalcoholic fatty liver disease (NAFLD). Exercise has been reported to have ameliorating effects on obesity and NAFLD. However, the underlying mechanism is not fully understood. We showed that liver expression of macrophage migration inhibitory factor (MIF) was increased after 4 weeks of treadmill exercise. Phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in human hepatocyte cell lines was enhanced after MIF treatment. These responses were accompanied by increases in lipid oxidation. Moreover, inhibition of either AMPK or cluster of differentiation 74 resulted in inhibition of MIF-induced lipid oxidation. Furthermore, the administration of MIF to a human hepatocyte cell line and mice liver reduced liver X receptor agonist-induced lipid accumulation. Taken together, these results indicate that MIF is highly expressed in the liver during physical exercise and may prevent hepatic steatosis by activating the AMPK pathway.</P>

Muscle over mind

( Hyo Youl Moon ) 대한운동사협회 2017 대한운동사협회 운동사대회자료집 Vol.2017 No.-

Differential expression of genes in the subgranular zone and granular cell layer of the hippocampus after running

( Hyo-youl Moon ) 한국운동영양학회 2018 Physical Activity and Nutrition (Phys Act Nutr) Vol.22 No.4

[Purpose] Despite numerous studies, the mechanisms underlying the effects of exercise on brain function are not yet fully understood. Adult hippocampal neurogenesis is one of the most well-known effects of exercise on the brain, but its physiological roles during exercise are still ambiguous, mostly due to the difference in the structure and composition of each part of the hippocampus. [Methods] In this study, we analyzed exercise-induced changes in gene expression in the subgranular zone (SGZ) and granular cell layer (GCL) of the hippocampus. [Results] Surprisingly, only about 10% of changes were common to both areas. Tollip expression, which is altered in the SGZ and in Engrailed-2 mutant mice following exercise, did not change in the GCL. Tollip levels were not changed in the whole hippocampus after two weeks of treadmill exercise, but immunofluorescence analysis showed that Tollip and Ki-67 co-localize in the hippocampal dentate gyrus . Through siRNA knockdown experiments, we found that levels of DCX and cellular survival rates were decreased in Tollip-deficient Neuro2A cells. [Conclusion] Taken together, these results suggest a role for Tollip in mediating the beneficial effects of exercise, probably affecting cellular health in the SGZ of the hippocampus.

Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells

Moon, Hyo Youl,Javadi, Sahar,Stremlau, Matthew,Yoon, Kyeong Jin,Becker, Benjamin,Kang, Sung-Ung,Zhao, Xinyu,van Praag, Henriette Elsevier Science B.V., Amsterdam. 2019 NEUROPHARMACOLOGY - Vol.145 No.no.pa

N-methyl D-aspartate receptor synaptonuclear signaling and neuronal migration factor (Nsmf) plays a novel role in myoblast proliferation.

Springer 2015 In vitro cellular & developmental biology Animal Vol.51 No.1

<P>Myogenesis, the formation and regeneration of muscular tissue, is a fundamental factor in embryonic development. N-methyl D-aspartate (NMDA) receptor synaptonuclear signaling and neuronal migration factor (Nsmf) mediates NMDA receptor endocytosis in GnRH neuronal cells. NMDA receptor is involved in myoblast differentiation by regulating Ca2 (+) dependent fusion of myocytes. In this study, we investigated the role of Nsmf in myoblast proliferation and differentiation. Quantitative-PCR, immunoblotting, and immunohistochemistry results showed that the Nsmf expression levels increased during both the differentiation and proliferation of myocytes. Knockdown of Nsmf in myocytes by siRNA did not affect the myocyte differentiation marker myogenin. However, flow cytometry showed that the proliferation rate of the Nsmf-knockdown cells was reduced compared to the control cells. Therefore, our results indicate that Nsmf is a novel myogenic factor that can enhance myoblast proliferation. Furthermore, Nsmf may be an important therapeutic target in diseases associated with aging, muscular dystrophy, or cachexia.</P>

임신 중 요통의 유병률 및 위험인자

문우남(Woo Nam Moon),한정렬(Jung Youl Han),임경택(Kyoung Taek Lim),오한진(Han Jin Oh),서승우(Seung Woo Suh),최영효(Young Hyo Choi) 대한정형외과학회 2000 대한정형외과학회지 Vol.35 No.4

국내 항생제 사용 실태조사 및 적정사용 방안에 관한 연구 : 2차년도

김준명,우준희,강문원,김양리,김효열,안형식 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.2

Exercise-induced AMPK activation is involved in delay of skeletal muscle senescence

Yoon, Kyeong Jin,Zhang, Didi,Kim, Seok-Jin,Lee, Min-Chul,Moon, Hyo Youl Elsevier 2019 Biochemical and biophysical research communication Vol.512 No.3

<P><B>Abstract</B></P> <P>Accumulation of senescent cells leads to aging related phenotypes in various organs. Sarcopenia is a frequently observed aging-related disease, which is associated with the loss of muscle mass and functional disability. Physical activity represents the most critical treatment method for preventing decreased muscle size, mass and strength. However, the underlying mechanism as to how physical activity provides this beneficial effect on muscle function has not yet been fully understood. In particular, one unresolved question about aging is how the boost in catabolism induced by aerobic exercise affects skeletal muscle atrophy and other senescence phenotypes.</P> <P>Here we show that pre-activation of AMPK with the AMPK activator, AICAR can mitigate the diminished cellular viability of skeletal muscle cells induced by doxorubicin, which accelerates senescence through free radical production. Pre-incubation for 3 h with AICAR decreased doxorubicin-induced phosphorylation of AMPK in a differentiated skeletal muscle cell line. Accordingly, cellular viability of skeletal muscle cells was recovered in the cells pre-treated with AICAR then administered doxorubicin as compared to that of doxorubicin-only treatment. In accordance with the results of cellular experiments, we verified that 4 weeks of treadmill exercise decreased the senescence marker, p16 and p21 in 19-month-old mice compared to sedentary mice.</P> <P>In this study, we provide new evidence that prior activation of AMPK can reduce doxorubicin induced cell senescence phenotypes. The evidence in this paper suggest that aerobic exercise-activated catabolism in the skeletal muscle may prevent cellular senescence, partially through the cell cycle regulation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Pre-treatment of AICAR attenuates phosphorylation of AMPK caused by Doxorubicin. </LI> <LI> Pre-treatment of AICAR prevent doxorubicin induced senescence phenotype of skeletal muscle cells. </LI> <LI> 4 week of treadmill exercise mitigates the acceleration of the skeletal muscle senescence in aged mice model. </LI> </UL> </P>

Associations between grip strength and glycemic control in type 2 diabetes mellitus: an analysis of data from the 2014-2019 Korea National Health and Nutrition Examination Survey

Harim Choe,Hoyong Sung,Geon Hui Kim,On Lee,Hyo Youl Moon,Yeon Soo Kim 한국역학회 2021 Epidemiology and Health Vol.43 No.-

OBJECTIVES: Glycemic control is essential for preventing severe complications in patients with diabetes mellitus. This study investigated the association between grip strength and glycemic control in Korean adults with type 2 diabetes mellitus. METHODS: From the Korea National Health and Nutrition Examination Survey, 2,498 participants aged over 19 years that patients with diabetes mellitus who did not have a history of cardiovascular disease or cancer were selected for analysis. Grip strength was assessed using a handheld dynamometer and was represented as age-specific and sex-specific tertiles. Multivariable logistic regression was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) of glycemic control according to the grip strength tertiles. RESULTS: A significantly lower probability (OR, 0.67; 95% CI, 0.47 to 0.97) for glycemic control was found in the lowest tertile of grip strength compared to the highest tertile. Furthermore, a subgroup analysis by sex only found significant associations between grip strength and glycemic control in males. CONCLUSIONS: Lower grip strength was associated with poor glycemic control in patients with diabetes mellitus, especially in males. However, further studies are needed to confirm the causal relationship between grip strength and glycemic control.