• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.455-464
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• 2021

Uncontrolled inflammation is considered the pathophysiological basis of many prevalent metabolic disorders, such as nonalcoholic fatty liver disease, diabetes, obesity, and neurodegenerative diseases. The inflammatory response is a self-limiting process that produces a superfamily of chemical mediators, called specialized proresolving mediators (SPMs). SPMs include the ω-3-derived family of molecules, such as resolvins, protectins, and maresins, as well as arachidonic acid-derived (ω-6) lipoxins that stimulate and promote resolution of inflammation, clearance of microbes, and alleviation of pain and promote tissue regeneration via novel mechanisms. SPMs function by binding and activating G protein-coupled receptors, such as FPR2/ALX, GPR32, and ERV1, and nuclear orphan receptors, such as RORα. Recently, several studies reported that SPMs have the potential to attenuate lipid metabolism disorders. However, the understanding of pharmacological aspects of SPMs, including tissue-specific biosynthesis, and specific SPM receptors and signaling pathways, is currently limited. Here, we summarize recent advances in the role of SPMs in resolution of inflammatory diseases with metabolic disorders, such as nonalcoholic fatty liver disease and obesity, obtained from preclinical animal studies. In addition, the known SPM receptors and their intracellular signaling are reviewed as targets of resolution of inflammation, and the currently available information on the therapeutic effects of major SPMs for metabolic disorders is summarized.

• Journal of Biomedical Engineering Research
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• v.43 no.1
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• pp.61-70
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• 2022

Natural and synthetic forms of calcium phosphate cement (CPC) have been widely used in bone repair and augmentation. The major challenge of injectable CPC is to deliver the cells without cell death in order to regenerate new bone. The study objective was to investigate for the potential of stem cell-laden gelatin fibers containing injectable, nanocrystalline CPC to function as a delivery system. Gelatin noddle fiber method was developed to delivered cells into nCPC. Experimental groups were prepared by mixing cells with nCPC, mixing cell-laden gelatin fibers with nCPC and mixing cell-laden gelatin fibers containing BMP-2 with nCPC. Media diffusion test was conducted after dissolving the gelatin fibers. SEM examined the generated channels and delivered cell morphology. Fibers mixed with nCPC showed physical setting and hardening within 20 min after injection and showed good shape maintenances. The gelatin fibers mixed nCPC group had several vacant channels generated from the dissolved gelatin. Particularly, proliferation and attachment of the cells were observed inside of the channels. While live cells were not observed in the cell mixed nCPC group, cells delivered with the gelatin fibers into the nCPC showed good viability and increased DNA content with culture. Cell-laden gelatin fiber was a novel method for cell delivery into nCPC without cell damages. Results also indicated the osteogenic differentiation of gelatin fiber delivered cells. We suggest that the cell-laden gelatin fibers mixed with nCPC can be used as an injectable cell delivery vehicle and the addition of BMP-2 to enhances osteogenesis.

• Korean Journal of Exercise Nutrition
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• v.24 no.3
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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.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.55-55
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• 2023

With the COVID-19 pandemic, there is increasing interest in anti-obesity strategies. According to the National Statistical Office, the obesity rate in Korea was 38.3% in 2020 and 37.1% in 2021. Obesity is a risk factor for several severe diseases, including stroke, heart disease, type 2 diabetes, and certain types of cancer. Pinus rigida × Pinus taeda is a hybrid of Pinus rigida Mill and Pinus taeda Linn, and its cones are considered a by-product. Although previous studies have investigated their pharmacological effects on antioxidant activity and protection against oxidative DNA damage, few researchers have explored their potential as functional natural materials. Therefore, we evaluated the anti-obesity effects of the cone of ethyl acetate fraction of P. rigida × P. taeda (ERT), specifically its ability to inhibit lipid accumulation. Our analysis showed that ERT contains phytochemicals (catechin and caffeic acid) which are known to improve immune function and inhibit cell damage. ERT inhibited lipid droplet accumulation at the cellular levels through Oil Red O staining. Furthermore, ERT suppressed the expression of adipogenic transcription factors (PPARγ and CEBP/α) as well as downstream lipogenic target genes (FAS and SREBP-1) thereby inhibiting adipogenesis. ERT also down-regulated key adipogenic markers, including aP2α, while inducing the phosphorylation of AMPK. It has been reported that PPARγ and CEBP/α are expressed in the early stages of adipose differentiation, while SREBP-1 is expressed in the late stage. Therefore, our findings suggest that ERT activates AMPK signaling pathways, which inhibits adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) and lipogenic genes (FAS and aP2α), thereby blocking lipid accumulation and preventing obesity and related disorders. ERT showed potential as a new resource for developing a functional material for anti-obesity agents.

• Journal of Life Science
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• v.27 no.11
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• pp.1357-1368
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• 2017

The purpose of this study was to investigate the anti-obesity and anti-inflammation effect of the cheonggukjang (a soybean paste fermented for only a few days) in diet induced obesity mice. Weight gain was significantly decreased in the mice fed cheonggukjang compared High Fat Diets (HFD). The HFD plus cheonggukjang (CGJ) were also effective in improving the lipid metabolism. The levels of plasma triglyceride, cholesterol, ALT, AST, leptin, glucose, and insulin were significantly lower in CGJ than HFD group (p<0.05). The adiponectin level of CGJ group was significantly increased compared to the HFD group (p<0.05). In the CGJ group, the mRNA expression of adipogenic genes in the liver and adipose tissues, which are transcription factors crucial for adipogenesis, were significantly suppressed (p<0.05). The number of $CD11b^+F4/80^+$ T cells, $Gr-1^{int}CD11b^{high}$ cells, and $Gr-1^{int}CD11b^{high}$ cells were significantly higher in HFD group than CGJ group (p<0.05). The size of adipocyte was significantly reduced in CGJ group compared to HFD group. In addition, the contents of liver lipid droplets were significantly downregulated in the CGJ mice than HFD mice (p<0.05). Collectively, these data suggest the novel function of cheonggukjang in modulating adipogenesis through an immune function-alteration involving downregulation of adipogenic transcription factors and macrophage activation.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Life Science
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• v.26 no.5
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• pp.519-530
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• 2016

Vegetative plants in Yakutia are naturally frozen when they are covered with snow in the fall, and they function as green cryo-fodder that is a source of biologically active substances and nutrients for herbivorous animals. We observed a considerable increase in the total fatty acid content in the leaves of Avena sativa, Elytrigia rеpens, Equisetum variegatum and Equisetum scirpoides during the fall period. However, the degree of unsaturation of fatty acids was not higher in the frozen plants covered with snow than in the summer plants, with the exception of E. scirpoides, a dwarf horsetail found in the Pole of Cold in the northern hemisphere. In the internal adipose tissue of the Yakut horse (young horse meat), 18 fatty acids were found, including 10 saturated ones. Monounsaturated oleic С18:1 (n-9) acid and polyunsaturated α-linolenic С18:3 (n-3) acid were equally prevalent among the unsaturated fatty acids, accounting for 70% of the total unsaturated fatty acids. This composition of polyenoic fatty acids in the internal adipose tissue indicates that the Yakut horse actively feeds on the fall vegetation and the wintergreen sedge-grass. We believe that the high plant-specific free fatty acid content in the tissue of Yakut horses may play an important role in the regulation of their resistance to long-term low-temperature stress.

• Journal of Life Science
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• v.19 no.1
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• pp.15-20
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• 2009

Uncoupling protein 3 (UCP3) is a mitochondrial protein that is expressed predominantly in skeletal muscle. It may play a role in altering metabolic function. However, its major physiological roles are not fully understood. Recently de novo expression of UCP3 in rat liver by fenofibrate was reported. We also reported previously that fenofibrate-induced de novo expression of UCP3 contributes to reduction of adipose tissue in obese rats. In the present study, we investigated that ienofibrate-induced expression of UCP3 in rat liver is related with metabolic function such as body weight and hepatic lipid content by time-dependent manner in high-fat diet rats. Eight-week-old male Sprague-Dawley rats were randomly divided into two groups; the high fat diet group (HF, n=16) and fenofibrate-treated high fat diet group (HFF, n=16). The mRNA expression of hepatic UCP3 was detected as early as 1 week of fenofibrate treatment by quantitative real-time PCR and the amount of mRNA was increased time-dependently. The mean body weight of the HFF group was significantly less com. pared with the HF group after 6 weeks of fenofibrate treatment, even though there was no difference of food intake between the two groups. Rectal temperature was increased during 4 to 6 weeks of fenofibrate treatment and body weight was decreased after 6 weeks of treatment. These results were corresponded with the increased amount of the expression of UCP3 mRNA and protein. We suggest that de novo expression of hepatic UCP3 is increased time-dependently with fenofibrate treatment and that the amount of expression is correlated with metabolic function.

• Applied Microscopy
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• v.39 no.4
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• pp.301-309
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• 2009

Estrogens induce pronounced structural and functional changes in male and female reproductive system, but the exact mechanisms of estrogen are not fully understood. In relation to estrogen's function, the present study was designed to identify effects of estrogen receptor agonist, 4,4',4"- (4-propyl-[1H]-pyrazole-1,3,5-triyl)tris phenol (PPT) in the reproductive organ of the female mouse. The PPT was subcutaneously given to adult female mice at a weekly dosage of 3 mg in a volume 0.06 mL of vehicle for 3, 5 or 8 weeks whereas controls received weekly injections of the castor oil vehicle. Effects of PPT on reproductive organs were analyzed using a light microscope. PPT induced decreases of body, ovary and adipose tissue weights with experimental time. Ovary diameter of PPT treatment group was reduced as compared with control group. The number of Graffian follicle and corpus luteum was reduced in PPT treatment group. The luminal diameter of uterus was increased in relation with decrease of myometrium and endometrium height by PPT administration. The number of uterine glands was decreased by PPT treatment. These data indicate that PPT treatment induced morphological change of female reproductive organs resulting in alteration of fertility.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.9
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• pp.1492-1500
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• 2004

The purpose of this study was to evaluate the effects of low calorie meal substitute and weight control preparation containing dietary fibers, ${\alpha}$-amylase inhibitor and hydroxycitrate on the reduction of body weight and visceral fat in obese women. Sixteen pre-menoposal healthy women (age: 20∼50 y, body mass index >25) who were living in the Daejeon area participated in this study. We replaced one meal of the subject with low calorie meal substitute and fed the weight control preparation twice a day for 9 weeks. Anthropometric indices, body composition, dietary intake and stool movements were investigated every 3 weeks during the dietary intervention. The blood was collected before and after the dietary intervention. Results are as follows: 1) The subjects' body weight, body fat, BMI, waist, hip and abdominal adipose tissue decreased gradually and significantly between 3rd and 9th week after intervention. 2) The levels of fasting blood glucose, triglyceride and cholesterol, the indicators of liver dysfunction such as activities of ALT, AST and ALP, and bilirubin level were within a normal range and not affected significantly by dietary intervention. 3) Hemoglobin levels increased significantly and blood urea nitrogen level decreased. 4) Their stool movement was improved 5) Compared with the baseline values, calorie intake decreased by 17.5∼21.9% and the intakes of vitamin A, vitamin B2, folate, Ca, Fe, and Zn were below 80% of Korean RDA. In conclusion, the intake of low calorie meal substitute and weight control preparation could be effective in reduction of body weight and fat mass, improving the stool movement and the general physical symptoms.