• 한국자원식물학회지
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• 제36권6호
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• pp.541-548
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• 2023

In the present study, the effects of HML on lipolysis, adipocyte browning, autophagy, and proliferation were investigated. HML affected lipolysis by increasing the protein levels of ATGL and HSL, and phosphorylation levels of HSL and AMPK. Furthermore, HSL decreased the perilipin-1 levels. In addition, free glycerol content was increased by HML treatment. HML affected adipocyte browning by increasing the protein levels of UCP-1, PGC-1α, and PRDM16. In addition, HML affected autophagy by increasing the levels of LC3-I and LC3-II, and decreasing those of SQSTM1/p62. Moreover, HML affected adipocyte proliferation by suppressing the proliferation of 3T3-L1 cells due to arrest of the cell cycle via blocking the expression of β-catenin and cyclin D1. These results suggest that HML induces lipolysis, adipocyte browning, autophagy, and inhibits excessive proliferation of adipocytes.

• Journal of Microbiology and Biotechnology
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• 제34권8호
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• pp.1688-1697
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• 2024

The current study aimed to determine whether Strongylocentrotus intermedius (S. intermedius) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and triglyceride content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 and peroxisome proliferator-activated receptor-γ coactivator 1α. Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.186-196
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• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• Journal of Ginseng Research
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• 제43권4호
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• pp.589-599
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• 2019

Background: Panax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated. Methods: 3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and realtime polymerase chain reaction, respectively. Results: Rg1 dramatically enhanced expression of brown adipocyte-especific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5' adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion. Conclusions: Rg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway.

• 식품과학과 산업
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• 제50권1호
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• pp.26-35
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• 2017

Obesity is a worldwide problem that is associated with metabolic disorders. Obesity is caused by the accumulation of an abnormal amount of body fat in adipose tissue. Adipose tissue is a major metabolic organ, and it has been classified as either white adipose tissue (WAT) or brown adipose tissue (BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and gene expression patterns. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides. On the other hand, BAT specializes in dissipating energy as heat through uncoupling protein-1 (UCP-1)-mediated non-shivering thermogenesis. Novel type of brown-like adipocyte within WAT called beige/brite cells was recently discovered, and this transdifferentiation process is referred to as the "browning" or "britening" of WAT. Recently, Brown fat and/or browning of WAT have been highlights as a new therapeutic target for treatment of obesity and its related metabolic disorders. Here, we describe recent advances in the study of BAT and browning of WAT, focusing on proteomic approaches.

• BMB Reports
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• 제55권10호
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• pp.500-505
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• 2022

Uncoupling protein 2 (Ucp2) was first introduced as a member of Uncoupling protein family and a regulator of ROS formation; however, its role in adipose tissue is not fully understood. In the present study, we have investigated the role of Ucp2 against high-fat diet (HFD)-induced obesity in epididymal white adipose tissue (eWAT) and browning of inguinal white adipose tissue (iWAT). Diet-induced obesity is closely related to macrophage infiltration and the secretion of pro-inflammatory cytokines. Macrophages surround adipocytes and form a crown-like-structure (CLS). Some reports have suggested that CLS formation requires adipocyte apoptosis. After 12 weeks of HFD challenge, Ucp2 knockout (KO) mice maintained relatively lean phenotypes compared to wild-type (WT) mice. In eWAT, macrophage infiltration, CLS formation, and inflammatory cytokines were reduced in HFD KO mice compared to HFD WT mice. Surprisingly, we found that apoptotic signals were also reduced in the Ucp2 KO mice. Our study suggests that Ucp2 deficiency may prevent diet-induced obesity by regulating adipocyte apoptosis. However, Ucp2 deficiency did not affect the browning capacity of iWAT.

• 대한의용생체공학회:의공학회지
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• 제45권1호
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• pp.43-48
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• 2024

The prevalence of obesity and its complications is steadily increasing worldwide. It is essential to understand cellular level metabolism and microenvironment to treat diseases related to lipid metabolism. Mechanical loading can activate signaling pathway by stimulating cells, especially vibration loading known to inhibit adipogenesis, so it has been studied as a treatment for obesity. Also, vibration loading can affect the inside of the human body non-invasively. Another clue to reducing adipose tissue is browning, which means that white adipocytes changes to brown adipocyte. In this study, we design and developed a device that that can control cell-cell contact, and vibration simulation device. Using these two devices, we investigated responses of cells to vibration loading. Protein expression associated with browning and adipogenesis were analyzed. In conclusion, vibration loading can be transmitted through cell contact and loading applied to the cells can induce browning and inhibit adipogenesis of preadipocytes. These results suggest the possibility that vibrations could be a treatment for obesity.

• 대한화장품학회지
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• 제48권4호
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• pp.331-342
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• 2022

비만은 에너지의 섭취와 소비의 불균형으로 인해 지방조직이 과도하게 분화하여 과잉 축적이 되면서 발생하게 되는 대사질환 중 하나이다. 본 연구에서 저자들은 3T3-L1 지방세포를 이용해 천연 유래 6 종 혼합물인 SliMax의 항비만 효과를 확인하였다. 그 결과 SliMax는 지방분화 단계에서 후기 분화를 조절하는 것으로 알려진 PPARγ와 C/EBPα의 발현 억제를 통해 지방분화를 억제하는 결과를 보였다. 또한 지방세포 분화 유도 후 지방세포 분해 과정에서 SliMax는 지방분해 관련 단백질인 ATGL과 HSL 발현 증가를 통해 큰 사이즈의 단방성 지방구를 작은 사이즈의 수많은 다방성 지방구로 분해하였다. 마지막으로 갈색지방으로 유도하는 효능을 확인하기 위해 UCP-1의 발현과 미토콘드리아 양을 면역형광염색법으로 확인한 결과 SliMax가 지방세포의 UCP-1의 발현과 미토콘드리아 양을 증가시켰다. 결과를 종합해볼 때, 천연 유래 혼합물인 SliMax는 지방 분화억제와 지방분해 촉진을 통해 지방구의 형성을 억제하고, 열 생산과 에너지 소비와 관련된 갈색지방화 촉진 기능을 가져 항비만 소재로의 가능성을 가진다.

• BMB Reports
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• 제53권3호
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• pp.142-147
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• 2020

Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation-related genes such as Ucp1, Pgc-1α, and Prdm16. Furthermore, structural analysis and western blot revealed that SA upregulates protein kinase A (PKA) phosphorylation with competitive inhibition by a pan-PKA inhibitor, H89. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. PKA-cat-α1 gene-silencing experiments confirmed that SA activates the thermogenic program via a mechanism involving PKA and cyclic AMP response element-binding protein (CREB) signaling. Moreover, SA treatment promoted lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation.

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권2호
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• pp.43-45
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• 2016

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. Serotonin is among those traditional pharmacological targets for anti-obesity treatment because central 5-HT functions as an anorexigenic neurotransmitter in the brain. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Fat specific Tph1 knock-out (Tph1 FKO) mice exhibit similar phenotypes as mice with pharmacological inhibition of 5-HT synthesis, suggesting the localized effects of 5-HT in adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure in BAT and Htr2a KO mice exhibit the decreased lipid accumulation in WAT. These data suggest the clinical significance of the peripheral serotonergic system as a new therapeutic target for anti-obesity treatment.