• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.725-732
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• 1998

In order to elucidate the molecular mechanism of the intracellular $Ca^{2+}$ overload frequently reported from diabetic heart, diabetic rats were induced by the administration of streptozotocin, the membrane vesicles of junctional SR (heavy SR, HSR) were isolated from the ventricular myocytes, and SR $Ca^{2+}$ uptake and SR $Ca^{2+}$ release were measured. The activity of SR $Ca^{2+}-ATPase$ was $562{\pm}14$ nmol/min/mg protein in control heart. The activity was decreased to $413{\pm}30$ nmol/min/mg protein in diabetic heart and it was partially recovered to $485{\pm}18$ nmol/min/mg protein in insulin-treated diabetic heart. A similar pattern was observed in SR $^{45}Ca^{2+}$ uptakes; the specific uptake was the highest in control heart and it was the lowest in diabetic heart. In SR $^{45}Ca^{2+}$ release experiment, the highest release, 45% of SR $^{45}Ca^{2+}$, was observed in control heart. The release of diabetic heart was 20% and it was 30% in insulin-treated diabetic heart. Our results showed that the activities of both SR $Ca^{2+}-ATPase$ and SR $Ca^{2+}$ release channel were decreased in diabetic heart. In order to evaluate how these two factors contribute to SR $Ca^{2+}$ storage, the activity of SR $Ca^{2+}-ATPase$ was measured in the uncoupled leaky vesicles. The uncoupling effect which is able to increase the activity of SR $Ca^{2+}-ATPase$ was observed in control heart; however, no significant increments of SR $Ca^{2+}-ATPase$ activities were measured in both diabetic and insulin-treated diabetic rats. These results represent that the $Ca^{2+}$ storage in SR is significantly depressed and, therefore, $Ca^{2+}-sequestering$ activity of SR may be also depressed in diabetic heart.

• 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.

• Animal Bioscience
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• v.35 no.7
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• pp.1010-1020
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• 2022

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

• Journal of the East Asian Society of Dietary Life
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• v.21 no.3
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• pp.463-470
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• 2011

The objective of this study was to examine the effects of a fruit diet and exercise on body composition and hematological parameters in female collegians according to their uncoupling protein 2 (UCP2) genotypes. Nine subjects were recruited from the SahmYook University. 4 subjects carried the ID genotype, 5 the DD genotype, and none of the subjects carried the II genotype. After 10 days of the program, BMI were significantly decreased (p<0.05) in the ID genotype and the DD genotype. Mean total energy intake from fruit diet was 888.1 kcal. Fat mass and % body fat were significantly decreased (p<0.05) in subjects with the ID genotype. Hemoglobin level was significantly increased (p<0.05) in subjects with the DD genotype. This study provided evidence that fruit diet and exercise could decrease the BMI in subjects with the ID and DD genotypes and increase the hemoglobin level in those with the DD genotype.

• BMB Reports
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• v.51 no.1
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• pp.39-44
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• 2018

Exchange protein directly activated by cAMP (Epac) 2a-knockout (KO) mice exhibit accelerated diet-induced obesity and are resistant to leptin-mediated adipostatic signaling from the hypothalamus to adipose tissue, with sustained food intake. However, the impact of Epac2a deficiency on hypothalamic regulation of sympathetic nervous activity (SNA) has not been elucidated. This study was performed to elucidate the response of Epac2a-KO mice to dexamethasone-induced muscle atrophy and acute cold stress. Compared to age-matched wild-type mice, Epac2a-KO mice showed higher energy expenditures and expression of myogenin and uncoupling protein-1 in skeletal muscle (SM) and brown adipose tissue (BAT), respectively. Epac2a-KO mice exhibited greater endurance to dexamethasone and cold stress. In wild-type mice, exogenous leptin mimicked the responses observed in Epac2a-KO mice. This suggests that leptin-mediated hypothalamic signaling toward SNA appears to be intact in these mice. Hence, the potentiated responses of SM and BAT may be due to their high plasma leptin levels.

• Journal of Korean Medicine for Obesity Research
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• v.12 no.2
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• pp.28-43
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• 2012

Objectives: The aim of the study was to investigate the efficacy of Boiogito for obesity. We examined the efficacy of Boiogito for obese patients and we expected the reaction of Boiogito would vary according to the single nucleotide polymorphism(SNPs). Methods: 111 subjects(body mass index${\geq}25m/kg^2$) were recruited and randomized to receive Boiogito(n=55) or Placebo(n=56) for 8weeks. Anthropometric factors, serum lipid profile, glucose, blood pressure(BP), pulse rate, resting metabolic rate and Korean version of obesity-related quality of life(KOQOL) scale measured at baseline and 8weeks. SNPs(${\beta}3$-adrenergic receptor(ADRB3), G protein ${\beta}3$(GNB3), peroxisome proliferator activated receptor gamma 2 gene(PPAR-${\gamma}2$), uncoupling protein(UCP2)) were conducted at baseline. Adverse reactions and safety outcome variables were also checked during trials. Results: Both groups showed significant improvement on obesity after treatment. Boiogito group decreased triglyceride than did control group and improved KOQOL. Boiogito showed a significant higher efficacy in C/T and T/T genotype of GNB3 gene / in Trp64 and Arg64 genotype of ADRB3 gene / in D/D genotype of UCP2 gene / in Pro/Pro genotype of PPAR-${\gamma}$ gene. Conclusions: Boiogito promoted obesity indexes without severe adverse reactions and proved its safety. Pharmacogenetical studies of Boiogito on obesity could be a effective method for the individualized treatment and prevention of obesity.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.269-277
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• 1995

Membrane vesicles were prepared by differential centrifugation from epithelial cells of porcine trachea. Total activity of microsomal ATPases was measured spectrophotometrically by a coupled enzyme assay. The steady-state activity of the enzyme was $329{\pm}10$ nmol/min mg protein. Thapsigargin, a specific antagonist of intracellular $Ca^{2+}-ATPase$, inhibited about 50% of the activity, leaving $178{\pm}18\;nmol/min .mg$ protein (n=6), indicating that the $Ca^{2+}-ATPase$ is one of the major microsomal ATPases. The microsomes used in this study appeared to be tight-sealed vesicles since they showed saturation in $^{45}Ca^{2+}$ uptake experiments. Inositol 1,4,5-trisphosphate $InsP_{3}, 4\;{\mu}M$, an agonist of $InsP_{3}$-sensitive $Ca^{2+}$ release channel ($InsP_{3}$, receptor), and Ca-ionophore A23187 $(10\;{\mu}M)$ induced $^{45}Ca^{2+}$ releases of 20% and 50% of stored $^{45}Ca^{2+}$, respectively. The addition of $(10\;{\mu}M\;InsP_{3}$ also increased the microsomal ATPase activity from $282{\pm}8$ nmol/min mg protein to $334{\pm}21$ nmol/min . mg protein in the intact vesicles. Similar increase in the activity was observed by making microsomes leaky (uncoupling) using the Ca-ionophore A23187. ;$InsP_{3}-induced$ effects were blocked by either thapsigargin or heparin suggesting that: 1) the $InsP_{3}-induced$ increase in ATPase activity is mediated by microsomal $Ca^{2+}-ATPase$, and 2) dissipation of $Ca^{2+}$ gradient across the microsomal membrane is responsible for the $InsP_{3}-induced$ effect. In order to test the dependence of the $Ca^{2+}-ATPase$ activity on the activity of $InsP_{3}-induced$ the activity of ATPases was monitored in various concentrations of free $Ca^{2+}$ using $EGTA-Ca^{2+}$ buffers. The $Ca^{2+}$-dependent biphasic change is the well-known character of $InsP_{3} receptor but not of microsomal $Ca^{2+}-ATPase$ in non-excitable cells; however, the activity of microsomal ATPase appeared biphasic and a maxim진 activity of $397{\pm}36nmol/min\;.mg$ protein was obtained in the solution containing 100 nM free $Ca^{2+}$. Below or above this concentration, the activity of ATPases was lower. These results strongly support a positive correlation of microsomal $Ca^{2+}-ATPase$ to the $InsP_{3}$ receptors in epithelial microsomes.

• Environmental Mutagens and Carcinogens
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• v.22 no.1
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• pp.39-46
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• 2002

Obesity is a complex metabolic disorder with a strong genetic component. There are many candidate genes for obesity and its related phenotypes. We studied genetic variations between Korean obese and lean groups. Polymorphisms investigated were the Msp I polymorphism of the $\alpha$$_{2A}$-adrenergic receptor ($\alpha$$_{2A}$-AR) gene, the Mnl I polymorphism of the $\alpha$$_2$-adrenergic receptor ($\alpha$$_2$-AR) gene, the BstO I polymorphism of the $\beta$$_3$-adrenergic receptor ($\beta$$_3$-AR) gene, the Pml I polymorphism of the lamin A/C (LMNA) gene, the Hga I polymorphism of the clearance receptor (NPRC) gene, the Msp I polymorphism of the leptin gene, BclI polymorphism of the uncoupling protein 1 (UCPI) gene and the Hha I polymorphism of the fatty acid binding protein 2 (FABP2) gene. Among these genetic markers, Pml I polymorphism at the LMNA gene and Bcl I polymorphism at the UCP1 gene were significantly associated with obesity. However, further studies are required whether thease findings are reproduced in large population, although two polymorphisms might be useful as genetic markers in the ethiology of obesity in Korean population.ion.

• Journal of Nutrition and Health
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• v.35 no.9
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• pp.903-911
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• 2002

The effects of dietary levan, high-molecular-weight $\beta$-2,6-linked fructose polymer, on adiposity, serum leptin and UCP expression in rats fed high fat diet were studied. The adipose tissue hormone, leptin has been proposed to be involved in the regulation of food intake and energy expenditure. Uncoupling protein (UCP), a mitochondrial protein that uncouples the respiratory chain from oxidative phosphorylation, generates heat instead of ATP, thereby increase energy expenditure. To determine whether the dietary levan may have the anti-obesity effect, 4 wk old Sprague Dawley male rats fed high fat diet for 6 wks to induce obesity, and subsequently fed one of three diets for further 6 wks: 1) high fat (40% of calories) diet without levan 2) with 3% (w/w) levan 3) with 5% levan. For the comparison, control group fed AIN-76A diet. Visceral and peritoneal fat masses were lower in high fat diet with levan groups compared to high fat diet group. The effect of levan was dose-dependent. Adipocyte size was significantly reduced in the levan diet groups compared to the no levan diet group. Serum cholesterol level was not affected by levan containing diet, while the serum HDL cholesterol level was higher in leven diet groups. In addition, serum triglyceride level was markedly reduced by levan containing diet, thus lower than that of control group. Serum leptin was reduced by levan containing diet and lower in 5% levan group compared to 3% levan group (p < 0.001), as a result, serum leptin and insulin levels of 5% levan group were reduced to level of control group. Futhermore, the serum leptin level reflected the adiposity. The expression of UCP 1, and UCP 2 in brown adipose tissue was up-regulated by levan containing diet. In conclusions, levan containing diet reduced adiposity and serum triglyceride but increased UCP expression in the obese rats fed high fat diet. (Korean J Nutrition 35(9) : 903~911, 2002)

• Journal of Nutrition and Health
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• v.57 no.4
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• pp.376-388
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• 2024

Purpose: Adipocyte dysfunction has been reported in diabetes, and stimulating thermogenesis and suppressing senescence in adipocytes potentially alleviates metabolic dysregulation. This study aimed to investigate thermogenesis and cellular senescence in diabetic adipocytes under basal conditions and in response to stimuli. Methods: White and brown primary adipocytes derived from control (CON) and db/db (DB) mice were treated with β-agonists, such as norepinephrine (NE) and CL316,243, and 18-carbon fatty acids, including stearic acid, oleic acid (OLA), linoleic acid (LNA), and α-linolenic acid, and the expression of the genes related to thermogenesis and cellular senescence was measured. Results: Although no difference in the thermogenic and cellular senescence gene expression in white adipose tissue (WAT) was noted between the CON and DB mice, brown adipose tissue (BAT) from the DB mice exhibited lower uncoupling protein 1 (Ucp1) expression and higher cyclin-dependent kinase inhibitor (Cdkn)1a and Cdkn2a expression levels compared to that from the CON mice. Stromal vascular cells isolated from the BAT of the DB mice displayed higher peroxisome proliferator-activated receptor gamma (Pparg), CCAAT/enhancer-binding protein alpha (Cebpa), Cdkn1a, and Cdkn2a expression levels. White adipocytes from the DB mice exhibited lower Ucp1, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a), and PR domain containing 16 (Prdm16) expression levels regardless of β-agonist treatment. NE upregulated Pgc1a in both white and brown adipocytes from the CON mice, but not in those from the DB mice. Although none of the fatty acids were observed to downregulate the cellular senescence genes in fully differentiated adipocytes, the OLA-treated brown adipocytes derived from DB mice exhibited lower Cdkn1a and Cdkn2b expression levels than the LNA-treated cells. Conclusion: These results indicate that the lower thermogenic capacity of diabetic adipocytes may be related to their cellular senescence, and different fatty acids potentially exert divergent effects on the expression of cellular senescence genes.