• Title/Summary/Keyword: ${\beta}_1$-adrenergic receptor (${\beta}_1-AR$)

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Neurogenic effect of exercise via the thioredoxin-1/ extracellular regulated kinase/β-catenin signaling pathway mediated by β2-adrenergic receptors in chronically stressed dentate gyrus

  • Kim, Mun-Hee;Leem, Yea-Hyun
    • Korean Journal of Exercise Nutrition
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    • v.23 no.3
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    • pp.13-21
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    • 2019
  • [Purpose] Chronic stress is a precipitating factor for depression, whereas exercise is beneficial for both the mood and cognitive process. The current study demonstrates the anti-depressive effects of regular exercise and the mechanisms linked to hippocampal neurogenesis. [Methods] Mice were subjected to 14 consecutive days of restraint, followed by 3 weeks of treadmill running, and were then subjected to behavioral tests that included the forced swimming and Y-maze tests. Protein levels were assessed using western blot analysis and newborn cells were detected using 5-bromo-2'-deoxyuridine (BrdU). [Results] Three weeks of treadmill running ameliorated the behavioral depression caused by 14 days of continuous restraint stress. The exercise regimen enhanced BrdU-labeled cells and class III β-tubulin levels in the hippocampal dentate gyrus, as well as those of thioredoxin-1 (TRX-1) and synaptosomal β2-adrenergic receptors (β2-AR) under stress. In vitro experiments involving treatment with recombinant human TRX-1 (rhTRX-1) augmented the levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear β-catenin, and proliferating cell nuclear antigens, which were previously inhibited by U0216 and FH535 (inhibitors of ERK1/2 and β-catenin/T cell factor-mediated transcription, respectively). The hippocampal neurogenesis elicited by a 7-day exercise regimen was abolished by a selective inhibitor of β2-AR, butoxamine. [Conclusion] These results suggest that TRX-1-mediated hippocampal neurogenesis by β2-AR function is a potential mechanism underlying the psychotropic effect of exercise.

Nrf2 induces Ucp1 expression in adipocytes in response to β3-AR stimulation and enhances oxygen consumption in high-fat diet-fed obese mice

  • Chang, Seo-Hyuk;Jang, Jaeyool;Oh, Seungjun;Yoon, Jung-Hoon;Jo, Dong-Gyu;Yun, Ui Jeong;Park, Kye Won
    • BMB Reports
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    • v.54 no.8
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    • pp.419-424
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    • 2021
  • Cold-induced norepinephrine activates β3-adrenergic receptors (β3-AR) to stimulate the kinase cascade and cAMP-response element-binding protein, leading to the induction of thermogenic gene expression including uncoupling protein 1 (Ucp1). Here, we showed that stimulation of the β3-AR by its agonists isoproterenol and CL316,243 in adipocytes increased the expression of Ucp1 and Heme Oxygenase 1 (Hmox1), the principal Nrf2 target gene, suggesting the functional interaction of Nrf2 with β3-AR signaling. The activation of Nrf2 by tert-butylhydroquinone and reactive oxygen species (ROS) production by glucose oxidase induced both Ucp1 and Hmox1 expression. The increased expression of Ucp1 and Hmox1 was significantly reduced in the presence of a Nrf2 chemical inhibitor or in Nrf2-deleted (knockout) adipocytes. Furthermore, Nrf2 directly activated the Ucp1 promoter, and this required DNA regions located at -3.7 and -2.0 kb of the transcription start site. The CL316,243-induced Ucp1 expression in adipocytes and oxygen consumption in obese mice were partly compromised in the absence of Nrf2 expression. These data provide additional insight into the role of Nrf2 in β3-AR-mediated Ucp1 expression and energy expenditure, further highlighting the utility of Nrf2-mediated thermogenic stimulation as a therapeutic approach to diet-induced obesity.

Anti-obesity Effects of Wolbi-tang(越婢湯) on the Obese-mice Induced by High-fat Diet (월비탕(越婢湯)이 고지방식이(高脂肪食餌)로 유도된 비만 생쥐에 미치는 영향)

  • Park, Ji-Hyun;Hong, Seo-Young
    • Journal of Korean Medicine Rehabilitation
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    • v.21 no.2
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    • pp.31-48
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    • 2011
  • Objectives : In order to investigate the anti-obesity effects of Wolbi-tang(here in after referred to WBT) on the obese gene and obese inhibitory, C57BL/6 mice were induced by high-fat diet. Methods : C57BL/6 mice were divided into 5 groups(normal, only high-fat diet, high-fat diet with Reductil, high-fat diet with WBT 400, 200 mg/kg extract) and fed for 5 weeks. And observed body weight change, total cholesterol, low density lipoprotein cholesterol(LDL-cholesterol), high density lipoprotein cholesterol (HDL-cholesterol), triglyceride, glucose, leptin change, alanine transaminase(ALT), aspartate transaminase(AST), serum creatinine, the expression of ${\beta}3$-adrenergic receptor(${\beta}3AR$), leptin, uncoupling protein(UCP2) gene in 3T3-L1 adipocyte, 3T3-L1 adipocyte proliferation, histological analysis of adipose tissue and liver tissue. Results : 1. Refer to cell cytotoxicity, viability of human fibroblast cells(hFCs) showed not significant changes. 2. The amount of ALT, AST was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. The amount of creatinine showed not significant changes. 3. Body weight was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. 4. The amount of total cholesterol and triglyceride was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. LDL-cholesterol was decreased and HDL-cholesterol was increased significantly in WBT 400 mg/kg groups. 5. The amount of glucose was decreased significantly in WBT 400 mg/kg groups. 6. The amount of serum leptin was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. 7. The revelation of ${\beta}3AR$ in 3T3-L1 adipocyte was increased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The revelation of leptin was decreased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The revelation of UCP2 was decreased significantly in WBT $100{\mu}g/ml$ group. 8. 3T3-L1 adipocyte proliferation was decreased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The size of adipocyte was decreased relative to the control group in WBT 400 mg/kg group. 9. The adipose vacuoles in liver tissue was decreased relative to the control group. Conclusions : These results suggested that WBT has inhibitory effects of obesity. WBT might be applicated on treatment of obesity and metabolic syndrome. Further studies analysing its effects were needed.

Alterations of Heart Rate Variability upon β3-Adrenergic Receptor Polymorphism and Combined Capsaicin, Sesamin, and L-Carnitine in Humans (복합 캡사이신, 세사인, 그리고 카르니틴과 베타3 유전자 다형에 대한 심박수 변이성의 영향)

  • Shin, Ki-Ok;Kim, Hyun-Jun;Kang, Sung-Hwun
    • Journal of Life Science
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    • v.18 no.3
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    • pp.291-297
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    • 2008
  • We investigated whether 1) the combined capsaicin (75 mg), sesamin (30 mg), and L-carnitine (900 mg) (CCSC) ingestion enhances autonomic nervous system (ANS) activities including thermogenic sympathetic activity as energy metabolic modulator, 2) ${\beta}_3-AR$ polymorphism of each subject influences with ANS activity. Seven healthy males $(22.0{\pm}0.5\;yr)$ volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis were continuously measured during 5 min every 30 min for total 120 min resting condition with CCSC or placebo oral administration chosen at random. The results indicated that, there are not $Arp/Arg^{64}$ variants of the ${\beta}_3-AR$ genotypes in our subjects. There were not also significant differences in heart rate during rest between both trials. The difference of ANS activity did not reach the statistical significance between both trials. However, the significant improvement showed TOTAL power, HF component, and the indices of SNS and PNS activities before and at 30 min after CCSC ingestion (p<0.05, respectively). In conclusions, although each component of combined CCSC is associated with lipolysis and/or fat oxidation, the combined CCSC consumption is not influenced in stimulation of thermogenic sympathetic activity as modulator of energy metabolism. In rather, our results suggested that CCSC ingestion improves the balance of both SNS and PNS activities. Therefore, it will be considered many combined nutrient components for ergogenic and/or lipolysis effects as well as genetic variants affecting ANS activity in further studies.