• Asian-Australasian Journal of Animal Sciences
• /
• 제22권4호
• /
• pp.576-583
• /
• 2009

G protein-coupled receptor 43 (GPR43) is a newly-discovered short-chain free fatty acid receptor and its functions remain to be defined. The objective of this study was to investigate the function of GPR43 on lipolysis. We successfully cloned the GPR43 gene from the pig (EU122439), and measured the level of GPR43 mRNA in different tissues and primary pig adipocytes. The expression level of GPR43 mRNA was higher in adipose tissue and increased gradually with adipocyte differentiation. Then we examined GPR43 mRNA level in different types, growth-stages and various regions of adipose tissue of pigs. The results showed that the expression level of GPR43 mRNA was significantly higher in adipose tissue of obese pigs than in lean pigs, and the expression level also gradually increased as age increased. We further found that the abundance of GPR43 mRNA level increased more in subcutaneous fat than visceral fat. Thereafter, we studied the correlation between GPR43 and lipid metabolism-related genes in adipose tissue and primary pig adipocytes. GPR43 gene had significant negative correlation with hormone-sensitive lipase gene (HSL, r = -0.881, p<0.01) and triacylglycerol hydrolase gene (TGH, r = -0.848, p<0.01) in adipose tissue, and had positive correlation with peroxisome proliferator-activated receptor $\gamma$ gene ($PPAR_{\gamma}$, r = 0.809, p<0.01) and lipoprotein lipase gene (LPL, r = 0.847, p<0.01) in adipocytes. In addition, we fed different concentrations of docosahexaenoic acid (DHA) to mice, and analyzed expression level changes of GPR43, HSL and TGH in adipose. The results showed that DHA down-regulated GPR43 and up-regulated HSL and TGH mRNA levels; GPR43 also had significant negative correlation with HSL (low: r = -0.762, p<0.01; high: r = -0.838, p<0.01) and TGH (low: r = -0.736, p<0.01; high: r = -0.586, p<0.01). Our results suggested that GPR43 is a potential factor which regulates lipolysis in adipose tissue, and DHA as a receptor of GPR43 might promote lipolysis through down-regulating the expression of GPR43 mRNA.

• Molecules and Cells
• /
• 제44권7호
• /
• pp.458-467
• /
• 2021

GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca²⁺ flux via coupling to Gα_i and Gα_q families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gα_q/11 and Gα_12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

• BMB Reports
• /
• 제47권3호
• /
• pp.173-178
• /
• 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.

• Biomolecules & Therapeutics
• /
• 제30권1호
• /
• pp.48-54
• /
• 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 Gα_i/o and Gα_q/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.

• The Korean Journal of Physiology and Pharmacology
• /
• 제28권1호
• /
• pp.1-10
• /
• 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.

• Geomechanics and Engineering
• /
• 제30권6호
• /
• pp.489-502
• /
• 2022

In this study, a Gaussian process regression (GPR) model as well as six GPR-based metaheuristic optimization models, including GPR-PSO, GPR-GWO, GPR-MVO, GPR-MFO, GPR-SCA, and GPR-SSO, were developed to predict fly-rock distance in the blasting operation of open pit mines. These models included GPR-SCA, GPR-SSO, GPR-MVO, and GPR. In the models that were obtained from the Soungun copper mine in Iran, a total of 300 datasets were used. These datasets included six input parameters and one output parameter (fly-rock). In order to conduct the assessment of the prediction outcomes, many statistical evaluation indices were used. In the end, it was determined that the performance prediction of the ML models to predict the fly-rock from high to low is GPR-PSO, GPR-GWO, GPR-MVO, GPR-MFO, GPR-SCA, GPR-SSO, and GPR with ranking scores of 66, 60, 54, 46, 43, 38, and 30 (for 5-fold method), respectively. These scores correspond in conclusion, the GPR-PSO model generated the most accurate findings, hence it was suggested that this model be used to forecast the fly-rock. In addition, the mutual information test, also known as MIT, was used in order to investigate the influence that each input parameter had on the fly-rock. In the end, it was determined that the stemming (T) parameter was the most effective of all the parameters on the fly-rock.

• Molecules and Cells
• /
• 제43권4호
• /
• pp.340-349
• /
• 2020

Oleoylethanolamide (OEA), a bioactive lipid in bone, is known as an endogenous ligand for G protein-coupled receptor 119 (GPR119). Here, we explored the effects of OEA on osteoclast differentiation, function, and survival. While OEA inhibits osteoclast resorptive function by disrupting actin cytoskeleton, it does not affect receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. OEA attenuates osteoclast spreading, blocks actin ring formation, and eventually impairs bone resorption. Mechanistically, OEA inhibits Rac activation in response to macrophage colony-stimulating factor (M-CSF), but not RANKL. Furthermore, the OEA-mediated cytoskeletal disorganization is abrogated by GPR119 knockdown using small hairpin RNA (shRNA), indicating that GPR119 is pivotal for osteoclast cytoskeletal organization. In addition, OEA induces apoptosis in both control and GPR119 shRNA-transduced osteoclasts, suggesting that GPR119 is not required for osteoclast apoptosis. Collectively, our findings reveal that OEA has inhibitory effects on osteoclast function and survival of mature osteoclasts via GPR119-dependent and GPR119-independent pathways, respectively.

• 헤리티지:역사와 과학
• /
• 제43권3호
• /
• pp.306-333
• /
• 2010

그동안 신라의 왕성이었던 월성에 대한 연구는 월성을 중심으로 한 도성제와 월성해자 발굴을 통한 월성 주변의 모습에 치중해 있었다. 그러나 2004년에 월성 지표조사보고서가 발간되고 시험적 성격으로서 GPR탐사가 월성 내에서 실시되면서 월성에 대한 학술적 관심은 성내부로 변화되었다. 다행히 경주 월성의 고고학적 기초학술 조사가 시작되고 사업의 일환으로 월성 전 지역에 대한 물리탐사를 2007년 3월부터 1년에 걸쳐 실시하게 되었다. 이번 조사의 기본 목적은 GPR탐사를 실시하여 시험탐사에서 확인된 매장유구를 월성 전체 지역에 대하여 영상화하는 것이다. 미리 설정한 격자망에 수많은 측선을 조밀하게 설치하여 3차원 GPR 탐사를 실시하였으며 총 조사면적은 $112,535m^2$이다. 분석은 Depth Slice를 실시하여 각 깊이별로 유구의 변화양상과 중복상황을 파악할 수 있도록 하였으며, Slice Overlay 분석법을 이용하여 각 깊이별 반사체를 하나의 도면으로 추출하였다. 또한 3차원 입체분석법인 Isolated Surface 영상화를 실시하여 유구 해석의 이해를 높였다. 그 결과 월성 내에서 총 14개의 구역으로 구분 지을 수 있는 크고 작은 건물지가 확인되었으며, 주목되는 곳은 월성의 서부(2구역), 중부(9구역), 동부(14구역)에 중요시설물일 것으로 짐작게 하는 대규모의 범상한 건물배치가 있는 3개의 구역이다. 본 연구결과를 통해서 3차원 GPR탐사는 광역적인 유적탐사에 매우 효과적이며 그 자료처리에 있어서 Slice Overlay 분석법은 지하 매장물에 대한 쉽고 뚜렷한 영상을 제공할 수 있음을 알 수 있었다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제33권4호
• /
• pp.651-661
• /
• 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.

• 생명과학회지
• /
• 제22권11호
• /
• pp.1571-1586
• /
• 2012

지구상에는 약 5,400여 종의 포유동물이 있고 그 중 약 1,000여 종은 풀을 뜯어 먹고 사는 초식동물이다. 초식동물 중에서 약 250여 종이 반추동물로 알려져 있다. 반추동물인 소와 양은 반추위에서 주로 발효가 일어나지만 비반추동물인 돼지와 사람은 맹장과 결장, 직장에서 주로 발효가 일어난다. 반추위 미생물의 종류와 우점도 Bacteroidetes 51%, Firmicutes 43% 존재하며, 사람의 대장미생물의 우점도Firmicutes 65%, Bacteroidetes 25%로 존재한다. 풀의 세포벽 구성성분은 미생물에 의해 분해, 발효에 의해 SCFA (short chain fatty acid)를 생성하게 되고 acetate, propionate, butyrate 생성비율은 60:25:15이다. 장내 primary butyrate transporter인 MCT1(monocarboxylatetransports-1)에 의해서 흡수된 butyrate는 SCFA receptor GPR43과 GPR41을 활성화시킨다. Butyrate는 강력한 anti-tumorigenic 기능을 가지고 있다. Butyrate는 다양한 cancer cell에 효과를 나타내며 세포내의 기능 조절에 기여하고, 암세포사멸을 유도하는 특성이 있다. Butyrate는 caspase의 활성화, HDAC (histone deacetylase) 활성을 억제하여apoptosis를 유도하고, p53 발현증가로 cell cycle arrest와 apoptosis를 유도한다. SCFA의 항 염증작용으로는 장 상피세포에서 IL-8 발현 감소, NO합성과 NF-${\kappa}B$ (nuclear factor ${\kappa}B$)의 활성을 억제하여 염증으로 인한 암 발생을 억제한다. Butyrate는 장 점막의 생리적 기능을 유지하는데 중요한 역할을 하며 IBD (inflammatory bowel disease) 치료법으로 이용되고 있다.