• Title/Summary/Keyword: GPR41

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Perspectives on the therapeutic potential of short-chain fatty acid receptors

  • Kim, Sunhong;Kim, Jeong-Hoon;Park, Bi Oh;Kwak, Young Shin
    • BMB Reports
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    • v.47 no.3
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    • pp.173-178
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    • 2014
  • There is rapidly growing interest in the human microbiome because of its implication in metabolic disorders and inflammatory diseases. Consequently, understanding the biology of short chain fatty acids and their receptors has become very important for identifying novel therapeutic avenues. GPR41 and GPR43 have been recognized as the cognate receptors for SCFAs and their roles in metabolism and inflammation have drawn much attention in recent years. GPR43 is highly expressed on immune cells and has been suggested to play a role in inflammatory diseases such as inflammatory bowel disease. Both GPR41 and GPR43 have been implicated in diabetes and obesity via the regulation of adipose tissue and gastrointestinal hormones. So far, many studies have provided contradictory results, and therefore further research is required to validate these receptors as drug targets. We will also discuss the synthetic modulators of GPR41 and GPR43 that are critical to understanding the functions of these receptors.

Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway

  • Yan Sun;Hai Qu;Xiaohong Niu;Ting Li;Lijuan Wang;Hairui Peng
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.1
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    • pp.1-10
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    • 2024
  • Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.

Novel GPR43 Agonists Exert an Anti-Inflammatory Effect in a Colitis Model

  • Park, Bi-Oh;Kang, Jong Soon;Paudel, Suresh;Park, Sung Goo;Park, Byoung Chul;Han, Sang-Bae;Kwak, Young-Shin;Kim, Jeong-Hoon;Kim, Sunhong
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.48-54
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    • 2022
  • GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gαi/o and Gαq/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca2+ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of pre-existing compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

Chromium acetate stimulates adipogenesis through regulation of gene expression and phosphorylation of adenosine monophosphate-activated protein kinase in bovine intramuscular or subcutaneous adipocytes

  • Kim, Jongkyoo;Chung, Kiyong;Johnson, Bradley J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.4
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    • pp.651-661
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    • 2020
  • Objective: We hypothesized that Cr source can alter adipogenic-related transcriptional regulations and cell signaling. Therefore, the objective of the study was to evaluate the biological effects of chromium acetate (CrAc) on bovine intramuscular (IM) and subcutaneous (SC) adipose cells. Methods: Bovine preadipocytes isolated from two different adipose tissue depots; IM and SC were used to evaluate the effect of CrAc treatment during differentiation on adipogenic gene expression. Adipocytes were incubated with various doses of CrAc: 0 (differentiation media only, control), 0.1, 1, and 10 μM. Cells were harvested and then analyzed by real-time quantitative polymerase chain reaction in order to measure the quantity of adenosine monophosphate-activated protein kinase-α (AMPK-α), CCAAT enhancer binding protein-β (C/EBPβ), G protein-coupled receptor 41 (GPR41), GPR43, peroxisome proliferator-activated receptor-γ (PPARγ), and stearoyl CoA desaturase (SCD) mRNA relative to ribosomal protein subunit 9 (RPS9). The ratio of phosphorylated-AMPK (pAMPK) to AMPK was determined using a western blot technique in order to determine changing concentration. Results: The high dose (10 μM) of CrAc increased C/EBPβ, in both IM (p = 0.02) and SC (p = 0.02). Expression of PPARγ was upregulated by 10 μM of CrAc in IM but not in SC. Expression of SCD was also increased in both IM and SC with 10 μM of CrAc treatment. Addition of CrAc did not alter gene expression of glucose transporter 4, GPR41, or GPR43 in both IM and SC adipocytes. Addition of CrAc, resulted in a decreased pAMPKα to AMPKα ration (p<0.01) in IM. Conclusion: These data may indicate that Cr source may influence lipid filling in IM adipocytes via inhibitory action of AMPK phosphorylation and upregulating expression of adipogenic genes.

Groundwater Level Trend Analysis for Long-term Prediction Basedon Gaussian Process Regression (가우시안 프로세스 회귀분석을 이용한 지하수위 추세분석 및 장기예측 연구)

  • Kim, Hyo Geon;Park, Eungyu;Jeong, Jina;Han, Weon Shik;Kim, Kue-Young
    • Journal of Soil and Groundwater Environment
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    • v.21 no.4
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    • pp.30-41
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    • 2016
  • The amount of groundwater related data is drastically increasing domestically from various sources since 2000. To justify the more expansive continuation of the data acquisition and to derive valuable implications from the data, continued employments of sophisticated and state-of-the-arts statistical tools in the analyses and predictions are important issue. In the present study, we employed a well established machine learning technique of Gaussian Process Regression (GPR) model in the trend analyses of groundwater level for the long-term change. The major benefit of GPR model is that the model provide not only the future predictions but also the associated uncertainty. In the study, the long-term predictions of groundwater level from the stations of National Groundwater Monitoring Network located within Han River Basin were exemplified as prediction cases based on the GPR model. In addition, a few types of groundwater change patterns were delineated (i.e., increasing, decreasing, and no trend) on the basis of the statistics acquired from GPR analyses. From the study, it was found that the majority of the monitoring stations has decreasing trend while small portion shows increasing or no trend. To further analyze the causes of the trend, the corresponding precipitation data were jointly analyzed by the same method (i.e., GPR). Based on the analyses, the major cause of decreasing trend of groundwater level is attributed to reduction of precipitation rate whereas a few of the stations show weak relationship between the pattern of groundwater level changes and precipitation.

A Study on the Safety Evaluation Technique of Sluice Culvert (하천제방 배수통문 정밀 안전진단기법 연구)

  • Yoon, Jong-Ryeol;Kim, Jin-Man;Choi, Bong-Hyuck
    • 한국지구물리탐사학회:학술대회논문집
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    • 2008.10a
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    • pp.41-46
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    • 2008
  • After choosing twenty sluice culverts located at national rivers by detailed appearance evaluation, hydraulic response test and acoustic televiewer in addition to surface geophysical explorations were carried out to investigate the cavities which exist at the boundary of sluice culvert and ground. Tapping, GPR, 3-D resistivity surveys and acoustic televiewer imagery obtained successful results in limited conditions according to characteristics of the sites. On the other hand, hydraulic response test successfully detected cavity existing at the lower part of sluice culvert and its continuity. However, hydraulic response test can not supply the quantitative informations on the scale and the shape of cavity. Thus it is very important for accurate investigation to make comprehensive interpretation after supplying various surveys proper to site characteristics.

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Use of Cellulose and Recent Research into Butyrate (섬유소의 이용과 butyrate의 최근 연구)

  • Yeo, Tae Jong;Choi, In Soon;Cho, Kwang Keun
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1571-1586
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    • 2012
  • On earth, there are about 5,400 kinds of mammals, of which about 1,000 kinds are herbivores. Among herbivores, about 250 kinds are known to be ruminants. As for cattle and sheep, which are ruminants, fermentation takes places mainly in their rumen; in contrast, for pigs and men, which are non-ruminants, fermentation takes place mainly in their caecum, colon, and rectum. As for the kind and dominance of rumen microorganisms, Bacteroidetes account for 51% and Firmicutes for 43%. As for the dominance of the large intestine microorganisms in men, Firmicutes account for 65% and Bacteroidetes for 25%. Cell wall components are decomposed by microorganisms, and short chain fatty acids (SCFAs) are generated through fermentation; the ratio of acetate, propionate, and butyrate generate is 60:25:15. Butyrate absorbed through the primary butyrate transporter MCT1 (mono carboxylate transports-1) in the intestines activates such SCFA receptors as GPR43 and GPR41. Butyrate has a strong anti-tumorigenic function. Butyrate is characterized by the fact that it has an effect on many cancer cells, contributes to the coordination of functions in the cells, and induces cancer apoptosis. Butyrate activates caspase but inhibits the activity of HDAC (histone deacetylase), so as to induce apoptosis. In addition, it increases p53 expression, so as to induce cell cycle arrest and apoptosis. Anti-inflammation actions of SCFA include the reduction of IL-8 expression in intestinal epithelial cells, the inhibition of NO synthesis, and the restraint of the activity of NF-${\kappa}B$ (nuclear factor ${\kappa}B$), so as to suppress the occurrence of cancers caused by inflammation. Butyrate plays an important role in maintaining physiological functions of intestinal mucous membranes and is used as a cure for inflammatory bowel disease (IBD).

Effects of Hyperbaric Oxygen and $\alpha$-Tocopherol on Skin Antioxidant Enzymes Defence in Rats

  • Kim, Jang-Shu;Kim, Chung-Hui;Kim, Gon-Sup;Hah, Dae-Sik;Park, Sun-Gun;Kim, Yang-Mi
    • Toxicological Research
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    • v.17 no.1
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    • pp.41-47
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    • 2001
  • In order to test the effects of hyperbaric oxygen (HBO) and $\alpha$-tocopherol on full-thickness skin grafts in rats, we peeformed full-thickness skin grafts bilaterally on rats. After surgery, we analyzed the tissue-concentrations of superoxide dismutase (SOD), catalase, and glutathione peroxidase(GPx)/reductase(GPr) on days 0, 2, 4, 7, 10, 14, 21 and 28. The four groups had similar patterns of change in SOD, catalase, GPx and GPr values. SOD increased initially, and was significantly increased at day 7, returning to the preoperative activity level on day 14 (control, HBO, and $\alpha$-tocopherol treated alone) and 28 (HBO plus $\alpha$-tocopherol). Catalase had a similar pattern of change as the SOD enzyme activity, except for the surgical control on day 2. Glutathione peroxidase/reductase activity in the four groups had a similar pat-tern of enzyme activity, with a significant increase from preoperative level on day 4, peaking during days 7 to 10, and returning to preoperative level on day 21(surgical control, HBO, and $\alpha$-tocopherol-treated alone) and 28 (HBO plus $\alpha$-tocopherol treated group). Hence, the clinical use of HBO and $\alpha$-tocopherol mixture can be recommended as an adjunctive treatment for free skin grafts in rats. But, the antioxidant used, its dose, and the timing of its administration, as well as, the exposure time and the pressure of HBO, should be the subject of further research.

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Expression of Maturation-Related Genes and Leptin during Sexual Maturation in the Female Goldfish: Effects of Exogenous Kisspeptin

  • Kim, Na Na;Choi, Young Jae;Oh, Sung-Yong;Choi, Cheol Young
    • Journal of Marine Life Science
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    • v.1 no.1
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    • pp.41-49
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    • 2016
  • Kisspeptin (Kiss) and its cognate receptor, kisspeptin receptor (KissR; G protein coupled receptor 54, GPR54), have recently been recognized as potent regulators of reproduction in teleosts. Additionally, leptin plays an important role in energy homeostasis and reproductive function in teleosts. The purpose of this study was to examine differences in the concentration of the hormones of the Kiss/KissR system and leptin and the expression of their underlying genes, all of which are involved in the sexual maturation of female goldfish, Carassius auratus, following treatment with Kiss. The expression levels of KissR increased after the Kiss injection. Furthermore, the peptide hormone leptin also increased after the injection (in vivo and in vitro). Additionally, the expression of GnRH and GTHs (GTHα, FSHβ, and LHβ) increased in the brain and pituitary (in vitro and in vitro). These results support the hypothesis that Kiss plays important roles in the direct regulation of the hypothalamus-pituitary-gonad axis and leptin in goldfish. Therefore, we suggest that Kiss system gene expression is correlated with energy balance and reproduction.

Pulse Radar Signal Processing Algorithm for Vehicle Detection (차량검지 시스템을 위한 펄스레이더 신호처리 알고리즘)

  • 고기원;우광준
    • Journal of the Institute of Electronics Engineers of Korea SC
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    • v.41 no.5
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    • pp.9-18
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    • 2004
  • This paper presents a vehicle detecting algorithm using microwave system signals. The Proposed algerian decides the breakpoint of signals using the likelihood criteria. The decided signals are segmented and simplified. The proposed searching algorithm uses the Euclid distance from the weighted signal data. We tested the proposed algorithm to compare with the segmentation which is a method using smoothing and edge detection. We confirm that the proposed algorithm is very useful for detecting vehicles by field test.