• Journal of Animal Science and Technology
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• v.63 no.4
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• pp.766-777
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• 2021

Bezafibrate, a fibrate drug used as a lipid-lowering agent to treat hyperlipidemia, is a pan-agonist of peroxisome proliferator-activated receptor alpha. It can enhance mitochondrial fatty acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis. After ovulation, oocytes may get arrested at the metaphase II (MII) stage until fertilization beyond optimal timing, which is termed as post-ovulatory aging. Post-ovulatory aging is a disease that degrades DNA, mitochondria, and oxidative system, and has a negative impact on embryo development and quality; however, the impact of bezafibrate during post-ovulatory aging has not been fully defined. In the present study, we assessed the ability of bezafibrate to prevent the progression of aging in in vitro conditions as well as the underlying mechanisms in pigs. An appropriate concentration of this drug (50 µM) was added, and then oxidative stress, reactive oxygen species downstream, mitochondrial biogenesis, and mitochondrial function were analyzed via immunofluorescence staining and real-time polymerase chain reaction. Bezafibrate significantly alleviated reactive oxygen species and ameliorated glutathione production simultaneously in oocytes and embryos. Moreover, it diminished H2A.X and attenuated CASPASE 3 expression produced by oxidative stress in oocytes and embryos. Furthermore, bezafibrate remarkably improved the mitochondrial function and blastocyst quality as well as markedly reduced the mitochondria/TOM20 ratio and mtDNA copy number. The elevated PARKIN level indicated that mitophagy was induced by bezafibrate treatment after post-ovulatory aging. Collectively, these results suggest that bezafibrate beneficially affects against porcine post-ovulatory oocyte aging in porcine by its antioxidant property and mitochondrial protection.

• Journal of Korean Medicine for Obesity Research
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• v.4 no.1
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• pp.139-160
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• 2004

The obesity is detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms(SNPs), some of which promote the development of obesity-related type 2 diabetes mellitus. Type 2 diabetes mellitus is a common multifactorial genetic syndrome, which is determined by several different genes and environmental factors. In this review, five major conclusions are reached: (1)To be clinically significant, SNPs must be relevant, prevalent, modifiable, and measurable. (2)Differences in SNPs may have been caused by famine, ultraviolet light, alcohol, climate, agricultural revolution. livestock, lactase persistence, and westernized lifestyle. (3)Candidate obesity genes of calorie intake restriction are SIM 1, MC3R, MC4R, AGRP, CART, CCK, CNTFR, DRD2, Ghrelin, 5-HT receptor, NPY, PON and those of energy metabolism are LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, PGC-1, Androgen receptor and those of fat mobilization are AGT, ACE, ADA, APM1, Apolipoproteins, PPAR, FABP, FOXC2, GCGR, $11-{\beta}HSDI$, LDLR, Hormonal sensitive lipase, Perilipin, $TNF-{\alpha}$, $TNF-{\beta}$ (4)Candidate obesity genes in the eastern are NPY, LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, ACE, APM1, PPAR, and FABP. (5)Candidate obesity genes in type 2 diabetes mellitus are MC3R, MC4R, B2AR, B3AR, ADA, APM1, PPAR, FABP, FOXC2, PC1, PC2, ABCC8, CAPN10, CYP19, CYP7, ENPP1, GCK, GYS1, IGF, IL-6, Insulin receptor, IRS, and LPL. The discovery of SNPs will lead to a greater understanding of the pathogenesis of obesity and to better diagnostics, treatment, and eventually prevention.

• Journal of Nutrition and Health
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• v.55 no.4
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• pp.462-475
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• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.474-483
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• 2016

Enzymatically modified isoquercitrin (EMIQ) is a mixture of quercetin glycodsides consisting of isoquercitrin and its ${\alpha}-glucosylated$ derivatives containing one to seven additional linear glucose moieties. The aim of this study was to assess whether or not EMIQ attenuates high-fat diet (HFD)-induced body weight gain and changes in plasma indices of obesity in mice. Male C57BL/6N mice were fed chow diet, HFD, and HFD containing 1.2% EMIQ for 10 weeks. EMIQ significantly (P<0.05) reduced body weight gain (-21%), total visceral fat-pad weights (-31%), and plasma levels of triglycerides (-17%), total cholesterol (-19%), and free fatty acids (-26%) in HFD-fed mice. EMIQ significantly increased protein kinase A (PKA) expression in the epididymal adipose tissue of HFD-fed mice. Expression of adipogenesis-related genes significantly decreased, whereas expression of fatty acid oxidation-related and thermogenesis-related genes increased in epididymal adipose tissue of EMIQ-fed mice compared with HFD-fed mice. These results suggest that the protective effects of EMIQ against HFD-induced adiposity in mice appear to be associated with PKA-mediated signaling cascades involved in adipogenesis, fatty acid oxidation, and thermogenesis in adipose tissue.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.2
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• pp.49-67
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• 2018

Objectives: This study was conducted to assess the effects of Hwanggimacmundong-tang extract (HM) on obese rats with estrogen deficiency. Methods: The experiments were performed with ovariectomized rats as estrogen-deficient obesity model. Rats were grouped NC (Normal Control Group; sham operation group), OC (Obesity Control Group; estrogen-deficient group), HML (20 mg/kg/day), HMH (100 mg/kg/day). HM was administered orally for six weeks. Body weights and serum lipid level were measured, and real-time PCR was performed to estimate the effect of HM on gene expression in liver. Results: HM decreased the total cholesterol and triglyceride in serum. And HM increased leptin, CPT1 gene expression in liver tissue of obese rats with estrogen deficiency. However HM decreased $PPAR{\gamma}$, $PGC-1{\alpha}$, HMGCR, CYP8B1, LPL, ACAT1, ACAT2, ApoB, ACOX gene expression in liver tissue of obese rats with estrogen deficiency. Conclusions: It is concluded that HM reduced total cholesterol and triglyceride in serum, and regulate gene expression related to lipid metabolism. These results indicate Hwanggimacmundong-tang that might have potential for treatment of obesity and complications during the menopause caused by estrogen-deficiency.

• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.645-650
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• 2019

Brown adipocytes have an important role in the regulation of energy balance through uncoupling protein-1 (UCP-1)-mediated nonshivering thermogenesis. Although brown adipocytes have been highlighted as a new therapeutic target for the treatment of metabolic diseases, such as obesity and type II diabetes in adult humans, the molecular mechanism underlying brown adipogenesis is not fully understood. We recently found that protein tyrosine phosphatase receptor type B (PTPRB) expression dramatically decreased during brown adipogenic differentiation. In this study, we investigated the functional roles of PTPRB and its regulatory mechanism during brown adipocyte differentiation. Ectopic expression of PTPRB led to a reduced brown adipocyte differentiation by suppressing the tyrosine phosphorylation of VEGFR2, whereas a catalytic inactive PTPRB mutant showed no effects on differentiation and phosphorylation. Consistently, the expression of brown adipocyte-related genes, such as UCP-1, $PGC-1{\alpha}$, PRDM16, $PPAR-{\gamma}$, and CIDEA, were significantly inhibited by PTPRB overexpression. Overall, these results suggest that PTPRB functions as a negative regulator of brown adipocyte differentiation through its phosphatase activity-dependent mechanism and may be used as a target protein for the regulation of obesity and type II diabetes.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2004.11a
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• pp.9-10
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• 2004

We developed a new panel of markers for the characterization of chicken PGCs. The results of immunostaining demonstrated that anti-SSEA-3, anti-SSEA-4, anti-integrin 6, and anti-integrin 1 antibodies. and STA and DBA bound specifically to chicken PGCs. These reagents could be used to characterize chicken PGCs together with conventional marker reagents such as PAS and anti-SSEA-1 antibody. We also showed that double staining of PGCs with the newly developed markers was feasible, which might contribute to rapid detection and accurate characterization of chicken PGCs.

• Molecules and Cells
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• v.39 no.7
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• pp.543-549
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• 2016

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.317-325
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• 2017

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.211-216
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• 2014

Endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and mitochondrial biogenesis were assessed following varying intensities of exercise training. The animals were randomly assigned to receive either low- (LIT, n=7) or high intensity training (HIT, n=7), or were assigned to a control group (n=7). Over 5 weeks, the animals in the LIT were exercised on a treadmill with a $10^{\circ}$ incline for 60 min at a speed of 20 m/min group, and in the HIT group at a speed of 34 m/min for 5 days a week. No statistically significant differences were found in the body weight, plasma triglyceride, and total cholesterol levels across the three groups, but fasting glucose and insulin levels were significantly lower in the exercise-trained groups. Additionally, no statistically significant differences were observed in the levels of PERK phosphorylation in skeletal muscles between the three groups. However, compared to the control and LIT groups, the level of BiP was lower in the HIT group. Compared to the control group, the levels of ATF4 in skeletal muscles and CHOP were significantly lower in the HIT group. The HIT group also showed increased PGC-$1{\alpha}$ mRNA expression in comparison with the control group. Furthermore, both of the trained groups showed higher levels of mitochondrial UCP3 than the control group. In summary, we found that a 5-week high-intensity exercise training routine resulted in increased mitochondrial biogenesis and decreased ER stress and apoptotic signaling in the skeletal muscle tissue of rats.