• Integrative Medicine Research
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• 제6권3호
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• pp.254-259
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• 2017

Background: Those classified as Tae-Eum (TE)-type people in Sasang constitutional medicine (SCM) are prone to obesity. Although extensive clinical observations have confirmed this tendency, the underlying physiological mechanisms are unknown. Here, we propose a novel hypothesis using integrative physiology to explain this phenomenon. Methods: Hypoactive lung function in the TE type indicates that respiration is attenuated at the cellular level - specifically, mitochondrial oxygen consumption. Because a functional reduction in cellular energy metabolism is suggestive of intrinsic hypoactivity in the consumption (or production) of metabolic energy, we reasoned that this tendency can readily cause weight gain via an increase in anabolism. Thus, this relationship can be derived from the graph of cellular metabolic power plotted against body weight. We analyzed the clinical data of 548 individuals to test this hypothesis. Results: The statistical analysis revealed that the cellular metabolic rate was lower in TEtype individuals and that their percentage of obesity (body mass index >25) was significantly higher compared to other constitutional groups. Conclusion: Lower cellular metabolic power can be an explanation for the obesity trend in TE type people.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.741-748
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• 1997

In the present study, we have investigated the effect of metabolic inhibition on the inward rectifier K current ($I_{K1}$). Using whole cell patch clamp technique we applied voltage ramp from +80 mV to -140 mV at a holding potential of -30 mV and recorded the whole cell current in single ventricular myocytes isolated from the rabbit heart. The current-voltage relationship showed N-shape (a large inward current and little outward current with a negative slope) which is a characteristic of $I_{K1}$. Application of 0.2 mM dinitrophenol (DNP, an uncoupler of oxidative phosphorylation as a tool for chemical hypoxia) to the bathing solution with the pipette solution containing 5 mM ATP, produced a gradual increase of outward current followed by a gradual decrease of inward current with little change in the reversal potential (-80 mV). The increase of outward current was reversed by glibenclamide ($10\;{\mu}M$), suggesting that it is caused by the activation of $K_{ATP}$. When DNP and glibenclamide were applied at the same time or glibenclamide was pretreated, DNP produced same degree of reduction in the magnitude of the inward current. These results show that metabolic inhibition induces not only the increase of $K_{ATP}$ channel but also the decrease of $I_{K1}$. Perfusing the cell with ATP-free pipette solution induced the changes very similar to those observed using DNP. Long exposure of DNP (30 min) or ATP-free pipette solution produced a marked decrease of both inward and outward current with a significant change in the reversal potential. Above results suggest that the decrease of $I_{K1}$ may contribute to the depolarisation of membrane potential during metabolic inhibition.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권5호
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• pp.425-431
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• 2005

The systems-level analysis of microbes with myriad of heterologous data generated by omics technologies has been applied to improve our understanding of cellular function and physiology and consequently to enhance production of various bioproducts. At the heart of this revolution resides in silico genome-scale metabolic model, In order to fully exploit the power of genome-scale model, a systematic approach employing user-friendly software is required. Metabolic flux analysis of genome-scale metabolic network is becoming widely employed to quantify the flux distribution and validate model-driven hypotheses. Here we describe the development of an upgraded MetaFluxNet which allows (1) construction of metabolic models connected to metabolic databases, (2) calculation of fluxes by metabolic flux analysis, (3) comparative flux analysis with flux-profile visualization, (4) the use of metabolic flux analysis markup language to enable models to be exchanged efficiently, and (5) the exporting of data from constraints-based flux analysis into various formats. MetaFluxNet also allows cellular physiology to be predicted and strategies for strain improvement to be developed from genome-based information on flux distributions. This integrated software environment promises to enhance our understanding on metabolic network at a whole organism level and to establish novel strategies for improving the properties of organisms for various biotechnological applications.

• 동의생리병리학회지
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• 제23권6호
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• pp.1241-1246
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• 2009

It has been suggested that Tae-Eum peoples are prone to obesity. Although extensive clinical observations have shown this tendency in Sasang Constitutional Medicine (SCM), no scientific hypothesis has been proposed to delineate its mechanism. According to SCM theory, Tae-Eum peoples have a hypoactive lung system and a hyperactive liver system. In this paper we propose a new hypothesis explaining the tendency of obesity in Tae-Eum people in the viewpoint of cell physiology. The hypoactive lung system might imply an attenuated 'respiration' at the cell/subcell level, namely mitochondrial oxygen consumption. Because a functional weakness in mitochondria energy metabolism indicates intrinsic hypo-activity in the consumption (or production) of metabolic energy, we deduced that the tendency can easily induce body weight gain via an increase in anabolism. This relation is also introduced in the graph of cellular metabolic power against body weight. To test this hypothesis, we analyzed the clinical data with 863 subjects. Statistical analysis of the data showed that Tae-Eum peoples had relatively a lower cellular metabolic power, and that the percentage of peoples with BMI>25 was significantly higher than that of the other constitutional types.

• The Korean Journal of Physiology and Pharmacology
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• 제26권1호
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• pp.15-24
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• 2022

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H₃R₉ exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H₃R₉ showed a better rescue action compared to that of MTS-H₃R₉. GA-MTS-H₃R₉ dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H₃R₉ towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTS-H₃R₉ alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H₃R₉ showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H₃R₉. We showed that GA-MTS-H₃R₉ can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

• Animal Bioscience
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• 제35권8호
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• pp.1184-1194
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• 2022

Objective: High concentrate diets are widely used to satisfy high-yielding dairy cows; however, long-term feeding of high concentrate diets can cause subacute ruminal acidosis (SARA). The endocrine disturbance is one of the important reasons for metabolic disorders caused by SARA. However, there is no current report about thyroid hormones involved in liver metabolic disorders induced by a high concentrate diet. Methods: In this study, 12 mid-lactating dairy cows were randomly assigned to HC (high concentrate) group (60% concentrate of dry matter, n = 6) and LC (low concentrate) group (40% concentrate of dry matter, n = 6). All cows were slaughtered on the 21st day, and the samples of blood and liver were collected to analyze the blood biochemistry, histological changes, thyroid hormones, and the expression of genes and proteins. Results: Compared with LC group, HC group showed decreased serum triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, increased hepatic glycogen, and glucose. For glucose metabolism, the gene and protein expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the liver were significantly up-regulated in HC group. For lipid metabolism, the expression of sterol regulatory element-binding protein 1, long-chain acyl-CoA synthetase 1, and fatty acid synthase in the liver was decreased in HC group, whereas carnitine palmitoyltransferase 1α and peroxisome proliferator activated receptor α were increased. Serum triiodothyronine, thyroxin, free triiodothyronine (FT3), and hepatic FT3 increased in HC group, accompanied by increased expression of thyroid hormone receptor (THR) in the liver. Conclusion: Taken together, thyroid hormones may increase hepatic gluconeogenesis, β-oxidation and reduce fatty acid synthesis through the THR pathway to participate in the metabolic disorders caused by a high concentrate diet.

• BMB Reports
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• 제54권11호
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• pp.575-580
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• 2021

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagy-related proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-week-old male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration.

• The Korean Journal of Physiology and Pharmacology
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• 제28권4호
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• pp.391-391
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• 2024

• Molecules and Cells
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• 제41권1호
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• pp.3-10
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• 2018

Autophagy is one of the major degradative mechanisms that can eliminate excessive nutrients, toxic protein aggregates, damaged organelles and invading microorganisms. In response to obesity and obesity-associated lipotoxic, proteotoxic and oxidative stresses, autophagy plays an essential role in maintaining physiological homeostasis. However, obesity and its associated stress insults can often interfere with the autophagic process through various mechanisms, which result in further aggravation of obesity-related metabolic pathologies in multiple metabolic organs. Paradoxically, inhibition of autophagy, within specific contexts, indirectly produces beneficial effects that can alleviate several detrimental consequences of obesity. In this minireview, we will provide a brief discussion about our current understanding of the impact of obesity on autophagy and the role of autophagy dysregulation in modulating obesity-associated pathological outcomes.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.127-127
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• 2023