• Journal of Ginseng Research
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• 제43권4호
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• pp.589-599
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• 2019

Background: Panax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated. Methods: 3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and realtime polymerase chain reaction, respectively. Results: Rg1 dramatically enhanced expression of brown adipocyte-especific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5' adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion. Conclusions: Rg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway.

• 한국체육학회지인문사회과학편
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• 제51권3호
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• pp.353-362
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• 2012

본 연구는 4주령의 male Wister rat을 대상으로 4주간 등열량 고지방식이 (50% calories from fat) 또는 지구성 운동 (treadmill running, slop 8%, 23m/min, 120분/일, 5일/주)이 미토콘드리아 생합성과 인슐린 저항성에 미치는 영향을 알아보는 것이다. 4주간의 등열량 고지방식이는 일반 사료 집단에 비해 체중과 체지방량에 차이가 없었고, 혈중 포도당, 인슐린 수준 및 골격근내의 인슐린 유발 포도당 이동률도 4주간 등열량 고지방식이 및 일반 사료 집단 간에 차이가 없는 것으로 나타났다. 4주간 등열량 고지방식이와 지구성 운동을 병해 실시한 집단의 체중, 체지방, 혈중 포도당 수준도 다른 3집단과 차이가 없는 것으로 나타났다. 그러나 지구성 운동을 실시한 집단은 고지방식이 집단보다 혈중 인슐린 수준이 유의하게(p<0.05) 낮게 나타났다. 4주간의 등열량 고지방식 또는 지구성 운동은 미토콘드리아 생합성을 증가시키지 않았으나 복합처치의 경우 유의하게(p<0.05) 증가시켰고, 이러한 현상은 혈중 유리지방산의 증가와 함께 나타났다(p<0.05). 이상의 연구 결과들을 종합하면 4주간의 등열량 고지방식과 지구성 운동 복합처치는 인슐린 저항성을 발생시키지 않고 미토콘드리아 표지인자를 유의하게 증가시킴으로 미토콘드리아 생합성을 안정적으로 증가시키는데 좋은 대안이 될 것으로 생각된다.

• 한국식품영양과학회지
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• 제44권3호
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• pp.324-330
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• 2015

본 연구에서는 C57BL/6J ob/ob 마우스를 이용하여 한국산 겨우살이 냉수 추출물(KME)의 항당뇨 활성을 조사하였다. 50 혹은 100 mg/kg의 KME를 1일 1회씩 경구투여 한 결과 KME 투여 개시 5일 후부터 ob/ob 마우스의 혈당이 유의하게 억제되었으며, 10일 후부터 안정된 억제 효과를 나타내고 대조군에 비해 20% 이상의 혈당강하 효과를 나타내었다. 경구 당부하 실험(OGTT)에서는 KME 경구투여 마우스에서 유효한 당부하 억제 활성이 관찰되었다. 또한 KME 경구 투여는 ob/ob 당뇨 마우스의 혈액 내 총 콜레스테롤과 중성 지질의 농도를 억제하는 것으로 나타났다. 한편 C2C12 근육세포를 이용한 in vitro 실험에서 KME를 처리함으로써 glucose uptake가 현저히 증가하였다. 한편 매우 흥미롭게도 KME를 처리한 C2C12 근육세포에 있어서 미토콘드리아 생성과 산화대사 조절물질인 peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}(PGC-1{\alpha})$를 비롯하여 glucose transporter type 4(GLUT4), estrogen-related receptor-${\alpha}(ERR-{\alpha})$, nuclear respiratory factor-1(NRF-1) 그리고 mitochondrial transcription factor A(TmfA)와 같은 $PGC-1{\alpha}$ 관련 유전자들의 발현이 증가하는 것으로 확인되었다. 이 결과는 KME가 2형 당뇨에 대한 치료물질로서의 작용을 지니며 이러한 KME의 항당뇨 활성은 미토콘드리아 생성의 조절과 관련 있는 것으로 추정된다.

• The Korean Journal of Physiology and Pharmacology
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• 제26권1호
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• pp.1-13
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• 2022

Kidney disease is becoming a global public health issue. Acute kidney injury (AKI) and chronic kidney disease (CKD) have serious adverse health outcomes. However, there is no effective therapy to treat these diseases. Lactoferrin (LF), a multi-functional glycoprotein, is protective against various pathophysiological conditions in various disease models. LF shows protective effects against AKI and CKD. LF reduces markers related to inflammation, oxidative stress, apoptosis, and kidney fibrosis, and induces autophagy and mitochondrial biogenesis in the kidney. Although there are no clinical trials of LF to treat kidney disease, several clinical trials and studies on LF-based drug development are ongoing. In this review, we discussed the possible kidney protective mechanisms of LF, as well as the pharmacological and therapeutic advances. The evidence suggests that LF may become a potent pharmacological agent to treat kidney diseases.

• Journal of Ginseng Research
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• 제44권2호
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• pp.341-349
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• 2020

Background: The replicative senescence of human dermal fibroblasts (HDFs) is accompanied by growth arrest. In our previous study, the treatment of senescent HDFs with Rg3(S) lowered the intrinsic reactive oxygen species (ROS) levels and reversed cellular senescence by inducing peroxiredoxin-3, an antioxidant enzyme. However, the signaling pathways involved in Rg3(S)-induced senescence reversal in HDFs and the relatedness of the stereoisomer Rg3(R) in corresponding signaling pathways are not known yet. Methods: We performed senescence-associated β-galactosidase and cell cycle assays in Rg3(S)-treated senescent HDFs. The levels of ROS, adenosine triphosphate (ATP), and cyclic adenosine monophosphate (cAMP) as well as the mitochondrial DNA copy number, nicotinamide adenine dinucleotide (NAD)⁺/1,4-dihydronicotinamide adenine dinucleotide (NADH) ratio, and NAD-dependent sirtuins expression were measured and compared among young, old, and Rg3(S)-pretreated old HDFs. Major signaling pathways of phosphatidylinositol 3-kinase/Akt, 5' adenosine monophosphate-activated protein kinase (AMPK), and sirtuin 1/3, including cell cycle regulatory proteins, were examined by immunoblot analysis. Results: Ginsenoside Rg3(S) reversed the replicative senescence of HDFs by restoring the ATP level and NAD⁺/NADH ratio in downregulated senescent HDFs. Rg3(S) recovered directly the cellular levels of ROS and the NAD⁺/NADH ratio in young HDFs inactivated by rotenone. Rg3(S) mainly downregulated phosphatidylinositol 3-kinase/Akt through the inhibition of mTOR by cell cycle regulators like p53/p21 in senescent HDFs, whereas Rg3(R) did not alter the corresponding signaling pathways. Rg3(S)-activated sirtuin 3/PGC1α to stimulate mitochondrial biogenesis. Conclusion: Cellular molecular analysis suggests that Rg3(S) specifically reverses the replicative senescence of HDFs by modulating Akt-mTOR-sirtuin signaling to promote the biogenesis of mitochondria.

• 생명과학회지
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• 제21권7호
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• pp.997-1003
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• 2011

폐경과 비만은 여러 대사증후군과 관련되어 있다. 이에 본 연구는 난소절제로 폐경을 유도한 흰쥐에게 고지방식이로 비만을 유도하여 이들 지방세포에서 발현되는 PPAR${\gamma}$, PGC-$1{\alpha}$, -$1{\beta}$, NRf-1, TFAM 유전자들의 변화를 조사하고 6주간의 규칙적인 운동을 하여 그 차이에 따른 효과를 규명하는데 목적을 두고 조사하였다. 본 실험에서 사용한 암컷흰쥐는 3그룹으로 다음과 같이 구분하였다. (1) 일반식이군(C group, n=4), (2) 고지방식이 군(H group, n=4), (3) 고지방식이와 운동군(H+EX group, n=4)으로 나누었다. 규칙적인 운동은 수영운동을 하였으며, 방법은 주 5회, 총 6주간 점진적 시간증가로 수행하였다. 그 결과, 지방조직의 무게는 H 그룹에서 유의하게 높게 (p<0.01) 나타났으나 규칙적인 운동그룹은 확실히 감소되었다. 또한 규칙적인 운동은 PPAR-${\gamma}$ (p<0.05), PGC-$1{\alpha}$ (p<0.01), -$1{\beta}$ (p<0.05), NRf-1 (p<0.01), TFAM (p<0.05)의 유전자들은 모두 유의하게 증가시켰다. 이상의 결과를 종합하면 6주간의 규칙적인 수영운동은 지방세포 내 PPAR-${\gamma}$, PGC-$1{\alpha}$, -$1{\beta}$, NRf-1, TFAM의 mRNA 발현 증가와 미토콘드리아의 수 증가에 영향을 미친 것으로 추측된다. 따라서 규칙적인 운동은 폐경기 비만으로 비대해진 피하지방을 감소시키고 지방세포 내 미토콘드리아의 생합성기능을 개선시켜 미토콘드리아 수 감소를 개선할 수 있을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.287-295
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• 2016

Involuntary physical activity induced by the avoidance of electrical shock leads to improved endurance exercise capacity in animals. However, it remains unknown whether voluntary stand-up physical activity (SPA) without forced simulating factors improves endurance exercise capacity in animals. We examined the effects of SPA on body weight, cardiac function, and endurance exercise capacity for 12 weeks. Twelve male Sprague-Dawley rats (aged 8 weeks, n=6 per group) were randomly assigned to a control group (CON) or a voluntary SPA group. The rats were induced to perform voluntary SPA (lifting a load equal to their body weight), while the food height (18.0 cm) in cages was increased progressively by 3.5 every 4 weeks until it reached 28.5 cm for 12 weeks. The SPA group showed a lower body weight compared to the CON group, but voluntary SPA did not affect the skeletal muscle and heart weights, food intake, and echocardiography results. Although the SPA group showed higher grip strength, running time, and distance compared to the CON group, the level of irisin, corticosterone, genetic expression of mitochondrial biogenesis, and nuclei numbers were not affected. These findings show that voluntary SPA without any forced stimuli in rats can effectively reduce body weight and enhance endurance exercise capacity, suggesting that it may be an important alternative strategy to enhance endurance exercise capacity.

• Journal of Nutrition and Health
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• 제57권1호
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• pp.53-64
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• 2024

본 연구는 근생성 효능을 가진 천연화합물을 발굴하고자 oxypeucedanin hydrate가 근생성과 미토콘드리아에 미치는 영향 및 항암제 유도 미토콘드리아 손상에 대한 완화효과를 C2C12 근원세포와 zebrafish 모델을 통해 각각 확인하였다. 그 결과, oxypeucedanin hydrate는 다핵의 근관세포의 수와 분화말기 표지자인 Myh4의 발현량을 증가시켰고 근육단백질 분해 인자인 MuRF1과 MAFbx의 발현량은 감소시켰다. 또한 미토콘드리아 생합성 조절인자인 Pgc1α, Tfam과 전자전달계 구성인자인 Sdha, Cox1의 발현은 증가시키고, 미토콘드리아 융합인자인 Opa1의 발현 또한 증가시킴과 동시에 미토콘드리아 분열을 표지하는 Drp1의 발현은 감소시켰다. 한편 zebrafish 모델을 통해 항암제 유도 미토콘드리아 손상에 대한 개선효과를 확인한 결과, oxypeucedanin hydrate는 항암제에 의해 유도된 미토콘드리아 손상을 완화시켰다. 이상의 결과들은 oxypeucedanin hydrate가 미토콘드리아 기능 증진을 매개로 근원세포 분화 촉진 및 근육 단백질 분해 저하 효과를 나타냄을 시사한다. 따라서 본 연구를 통해 oxypeucedanin hydrate가 근생성 효과를 나타낼 수 있는 잠재적인 유효소재로서의 가능성을 제시하였다.

• 운동영양학회지
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• 제24권3호
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• pp.13-18
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• 2020

[Purpose] In vivo studies have demonstrated the ergogenic benefits of eleutherococcus senticosus (ES) supplementation. ES has been observed to enhance endurance capacity, improve cardiovascular function, and alter metabolic functions (e.g., increased fat utilization); however, the exact mechanisms involved remain unknown. We aimed to determine whether ES could effectively induce fat loss and improve muscle metabolic profiles through increases in lipolysis- and lipid metabolism-associated protein expression in 3T3-L1 adipocytes and C2C12 skeletal muscle cells, respectively, to uncover the direct effects of ES on adipocytes and skeletal muscle cells. [Methods] Different doses of ES extracts (0.2, 0.5, and 1.0 mg/mL) were added to cells (0.2 ES, 0.5 ES, and 1.0 ES, respectively) for 72 h and compared to the vehicle control (control). [Results] The intracellular triacylglycerol (TG) content significantly decreased (p < 0.05 for 0.2 ES, p < 0.01 for 0.5 ES and 1.0 ES) in 3T3-L1 cells. Adipose triglyceride lipase, which is involved in active lipolysis, was significantly higher in the 1.0 ES group than in the control group (p < 0.01) of 3T3-L1 adipocytes. In C2C12 cells, the mitochondrial protein voltage-dependent anion channel (VDAC) was significantly increased in the 1.0 ES group (p < 0.01). Furthermore, we found that 1.0 ES activated both 5' AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in skeletal muscle cells (p < 0.01). [Conclusion] These findings suggest that ES extracts decreased TG content, presumably by increasing lipase in adipocytes and metabolism-associated protein expression as well as mitochondrial biogenesis in muscle cells. These effects may corroborate previous in vivo findings regarding the ergogenic effects of ES supplementation.

• Fisheries and Aquatic Sciences
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• 제27권2호
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• pp.122-135
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• 2024

Obesity is a disease involving mechanisms of fat accumulation, low-grade inflammatory cytokine release, and mitochondrial dysfunction. The aim of the current study was to investigate the effects of abalone intestine extract on fat metabolism in 3T3-L1 adipocytes and high fat diet-induced zebrafish larvae. The total phenol content was highest in subcritical water extract at 210℃ (SW210) among hot water, ethanol, and subcritical water extracts of abalone intestine. In addition, SW210 of male abalone intestine (MASW210) most effectively controlled the lipid accumulation and expression of adipogenic or lipogenic regulators (PPAR-γ, C/EBPα, SREBP-1c, and FAS) in 3T3-L1 adipocytes. Likewise, in zebrafish larvae fed high fat, MASW210 significantly suppressed body weight, glucose levels, and lipid accumulation. The mRNA expression related to adipogenesis (PPAR-γ and C/EBPα), lipogenesis (SREBP-1c and FAS), inflammatory cytokines (TNF-α and IL-6), energy m/;.etabolism (AMPK, lepr, SIRT1, and adiponectin), and mitochondrial biogenesis (PGC-1α and CPT-1) were significantly regulated by treatment with MASW210. These results suggest that abalone intestine extract such as MASW210, are useful biomaterials for improving obesity and metabolic diseases.