• Preventive Nutrition and Food Science
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• v.21 no.1
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• pp.62-67
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• 2016

Green tea (Camellia sinensis) is one of the most popular beverages in the world and has been acknowledged for centuries as having significant health benefits. (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea, and it has been reported to have health benefit effects. Peroxisome proliferator-activated receptor ${\gamma}$ coactivator $(PGC)-1{\alpha}$ is a crucial regulator of mitochondrial biogenesis and hepatic gluconeogenesis. The objective of this study was to investigate whether EGCG from green tea can affect the ability of transcriptional regulation on $PGC-1{\alpha}$ mRNA expression in HepG2 cells and 3T3-L1 adipocytes. To study the molecular mechanism that allows EGCG to control $PGC-1{\alpha}$ expression, the promoter activity levels of $PGC-1{\alpha}$ were examined. The $PGC-1{\alpha}$ mRNA level was measured using quantitative real-time PCR. The -970/+412 bp of $PGC-1{\alpha}$ promoter was subcloned into the pGL3-Basic vector that includes luciferase as a reporter gene. EGCG was found to up-regulate the $PGC-1{\alpha}$ mRNA levels significantly with $10{\mu}mol/L$ of EGCG in HepG2 cells and differentiated 3T3-L1 adipocytes. $PGC-1{\alpha}$ promoter activity was also increased by treatment with $10{\mu}mol/L$ of EGCG in both cells. These results suggest that EGCG may induce $PGC-1{\alpha}$ gene expression, potentially through promoter activation.

• Preventive Nutrition and Food Science
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• v.21 no.4
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• pp.317-322
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• 2016

Mitochondrial biogenesis is a complex process requiring coordinated expression of nuclear and mitochondrial genomes. The peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-$1{\alpha}$) is a key regulator of mitochondrial biogenesis, and it controls mitochondrial DNA (mtDNA) replication within diverse tissues, including muscle tissue. The aim of this study was to investigate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mtDNA copy number and PGC-$1{\alpha}$ promoter activity in $C_2C_{12}$ muscle cells. mtDNA copy number and mRNA levels of genes related to mitochondrial biogenesis such as PGC-$1{\alpha}$, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam) were assayed by quantitative real-time PCR. The PGC-$1{\alpha}$ promoter from -970 to +412 bp was subcloned into the pGL3-basic vector, which includes a luciferase reporter gene. Both EPA and DHA significantly increased mtDNA copy number, dose and time dependently, and up-regulated mRNA levels of PGC-$1{\alpha}$, NRF1, and Tfam. Furthermore, EPA and DHA stimulated PGC-$1{\alpha}$ promoter activity in a dose-dependent manner. These results suggest that EPA and DHA may modulate mitochondrial biogenesis, which was partially associated with increased mtDNA replication and PGC-$1{\alpha}$ gene expression in $C_2C_{12}$ muscle cells.

• Biomedical Science Letters
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• v.18 no.2
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• pp.139-145
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• 2012

RFLP of PGC-$1{\alpha}$ gene of 285 Korean women was analyzed by PCR and HpaII restriction. We evaluated the correlation between PGC 1 genotypes and biochemical results, using the results of RFLP. Study subjects were divided into 3 groups: normal group (who has been average value of serum biochemical analysis), upper group (who has been higher value than average value), and low group (who have been lower value than average value). The frequencies of $H_1H_1$, $H_1H_2$, and $H_2H_2$ genotypes were 92 (32%), 85 (32%), and 108 (38%) respectively, and the ratio between $H_1$ and $H_2$ alleles was 1:1.1. There were no meaningful differences between biochemical results and PGC-$1{\alpha}$ genotypes in the normal group. But, in upper group, there was significant difference in total cholesterol (P=0.04) level. In the result of Turkey multiple comparison test, the P value of $H_1H_1$ and $H_2H_2$ was 0.059. In upper group, there were noticeable differences also in triglyceride (P=0.034) level and glucose (P=0.043) level, respectively. There were important differences between $H_1H_1$ type and $H_1H_2$ type in triglyceride (P=0.029) level and between $H_1H_2$ type and $H_2H_2$ type in glucose (P=0.040) level. This study may provide the PGC-$1{\alpha}$ genotype patterns for the amounts of lipid and glucose in the serum. $H_2$ allele (Ser482) of PGC-$1{\alpha}$ gene may be related with upper group in Korean women.

• Molecules and Cells
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• v.39 no.2
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• pp.87-95
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• 2016

Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1's deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1's role in caloric restriction and impacts on longevity. The notion of Sirt1's regulation of PGC-$1{\alpha}$ activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1's regulation of mitochondrial biogenesis and turnover, in relation to PGC-$1{\alpha}$ deacetylation and various aspects of cellular physiology and disease.

• Journal of Life Science
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• v.28 no.7
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• pp.857-863
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• 2018

This study examined whether the supplementation of Salicornia herbacea L. (SH), a member of the Chenopodiaceae subfamily, affects tissue specific triglyceride (TG) accumulation and the peroxisome proliferator-activated $receptor-{\gamma}$ $coactivator-1{\alpha}$ ($PGC-1{\alpha}$) and peroxisome proliferator-activated $receptor-{\gamma}$ ($PPAR-{\gamma}$) protein expressions of skeletal muscle in rats with a high-fat diet. Sprague-Dawley male rats were randomly divided into three groups: control normal diet group (CD), high-fat diet group (HD), and 5.0% SH supplemented high-fat diet group (SD). The weights of fat tissue of the SD group were reduced by approximately 25%(p<0.01), while the skeletal muscle weight of the SD group increased approximately 5% compared to those in the HD group (p<0.01). The serum and hepatic TG of the SD group decreased approximately 20% compared to those of the HD group (p<0.05). In the protein expression levels in the skeletal muscle, the $PGC-1{\alpha}$ and $PPAR-{\gamma}$ expressions of the SD group were 1.5-folds higher than those of the HD group (p<0.01). From these results, SH supplementation contributes to the improvement of the serum and hepatic TG concentrations, and the $PGC-1{\alpha}$ and $PPAR-{\gamma}$ protein expression levels in the skeletal muscle of fed a high-fat diet. Thus, SH supplementation was effective in reducing fat mass and increasing muscle mass.

• Journal of Life Science
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• v.24 no.1
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• pp.67-73
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• 2014

This study was conducted to investigate the effects of supplementation with Opuntia humifusa on the expression of peroxisome proliferator-activated receptor-delta (PPAR-${\delta}$), peroxisome proliferator-activated receptor-gamma (PPAR-${\gamma}$) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-$1{\alpha}$) in the skeletal muscle of rats fed a high-fat diet. Sixteen Sprague-Dawley male rats at 6 weeks of age were randomly divided into 2 groups: a control diet group (CG, n=8) and an experimental diet group (EG, n=8). The rats were fed a high-fat diet (CG) or a high-fat diet supplemented with 5% O. humifusa (EG) for 8 weeks. The results showed that the abdominal fat pad and epididymal fat pad weights were significantly lower in the EG than in the CG (p<0.01). In the blood, serum glucose, triglycerides, and total cholesterol in the EG group were lower than in the CG (p<0.01). The expression of PPAR-${\gamma}$ and PGC-$1{\alpha}$ protein in the skeletal muscle of the EG was increased compared with that of the CG (p<0.05). These results indicate that 8 weeks of O. humifusa supplementation lowers serum glucose and triglyceride levels and suppresses weight gain by reducing fat weight through an increase in the expression of PPAR-${\gamma}$ and PGC-$1{\alpha}$ in the muscle tissue of rats.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.240-249
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• 2020

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.7
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• pp.963-971
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• 2014

This study investigated the effects of exercise intensity on PGC-$1{\alpha}$, PPAR-${\gamma}$, and insulin resistance in skeletal muscle of high fat diet-fed Sprague-Dawley rats. Forty rats were randomly divided into five groups: sedentary control group (SED), high fat diet group (HF), high fat diet+low-intensity exercise group (HFLE, 22 m/min, 60 min, 6 days/week), high fat diet+moderate-intensity exercise group (HFME, 26 m/min, 51 min), and high fat diet+high-intensity exercise group (HFHE, 30 m/min, 46 min). After 4 weeks of high fat diet and endurance exercise training, the lipid profiles, insulin, and glucose concentrations were determined in plasma. PGC-$1{\alpha}$, PPAR-${\gamma}$, and GLUT-4 contents were measured in plantaris muscle. The rate of glucose transport in soleus muscle was determined under submaximal insulin concentration ($1,000{\mu}IU/mL$ insulin, 20 min) during muscle incubation. Plasma glucose during oral glucose tolerance test in HF was significantly greater than that in SED, and plasma glucose levels in the three exercise (EX) groups were significantly lower that those in SED and HF at 30 and 60 min, respectively (P<0.05). Plasma insulin levels in the EX groups were significantly reduced by 60 min compared to that in HF (P<0.05). The protein expression level of PGC-$1{\alpha}$ as well as muscle glucose uptake were significantly higher in SED and HF than those in the three EX groups (P<0.05), and HFHE showed significantly higher levels than HFLE and HFME. Expression levels of GLUT-4 and PPAR-${\gamma}$ were significantly higher in the HFLE, HFME, and HFHE groups compared to the SED and HF (P<0.05). Therefore, the results of this study indicate that 4 weeks of high fat diet significantly developed whole body insulin resistance but did not affect PGC-$1{\alpha}$, PPAR-${\gamma}$, or the glucose transport rate in skeletal muscle, and exercise training was able to attenuate deteriorated whole body insulin resistance due to high fat diet. In addition, high intensity training significantly affected PGC-$1{\alpha}$ expression and the glucose transport rate of skeletal muscle in comparison with low and middle training intensities.

• 한국체육학회지인문사회과학편
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• v.55 no.4
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• pp.507-516
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• 2016

The purpose of this study is to identify the effects of PPARβ/δ over-expression on PGC-1α mRNA and protein stability after single bout of swimming exercise in mice skeletal muscle. Empty vector (EV) or PPARβ/δ was over-expressed in tibialis anterior(TA) using electroporation(EPO) technique to compare with non-treatment muscle(control; Con). TA muscles were dissected at 0h, 24h or 54h after termination of exercise. PGC-1α mRNA in Con, EV and PPARβ/δ over-expressed muscles were increased 6.8 fold (p<.001), 6.2 fold(p<.001) and 7.1 fold(p<.001), respectively, than sedentary(Sed) group at 0h after exercise and then reverted to Sed group levels at 24h and 54h after termination of exercise. PGC-1α and PGC-1α ubiquitination in EV treated muscles were increased 2.2 fold and 1.74 fold, respectively, than Sed group at 24h after termination of exercise, and then reverted to Sed group levels at 54h after termination of exercise. PGC-1α in PPARβ/δ over-expressed muscles at 24h and 54h after termination of exercise were increased 2.5 fold and 2.2 fold, respectively, than Sed group, but PGC-1α ubiquitination was not increased at 24h and 54h after termination of exercise. Our results indicate that PPARβ/δ over-expression does not increase PGC-1α mRNA stability, but increase PGC-1α protein stability through post-translation mechanism after termination of exercise.

• The Korean Journal of Food And Nutrition
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• v.30 no.5
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• pp.900-907
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• 2017

This study was performed to investigate the body fat-lowering effect of garlic powder in peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$)-luciferase transgenic mice (TG). In this study, we generated transgenic mice with a PGC-$1{\alpha}$ promoter (-970/+412 bp) containing luciferase as a reporter gene. Mice were fed a 45% high-fat diet for 8 weeks to induce obesity. Subsequently, mice were maintained on either a high-fat control diet (CON), or high-fat diets supplemented with 2% (GP2) or 5% (GP5) garlic powder for an additional 8 weeks. Dietary garlic powder reduced the body weight in the GP2 and GP5 groups, compared to the CON group. Furthermore, garlic supplementation significantly decreased the plasma levels of triglycerides, total cholesterol, and leptin in the GP5 group, compared to the CON group. Specifically, luciferase activity in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) was increased by garlic supplementation in a dose-dependent manner. These results suggest that the body fat-lowering effect of garlic powder might be related to PGC-$1{\alpha}$ by the increase in luciferase activity in liver, WAT, and BAT. Furthermore, transgenic mice might be useful for evaluating the body fat-lowering effect of various health functional foods.