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The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesWhite adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesWhite adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesThe sclera maintains and protects the eye ball, which receives visual inputs. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. We have here demonstrated microarray data of cultured human scleral cells.
Human sclera maintains common characteristics with cartilage throughout evolution.
No sample metadata fields
View SamplesIllumina sequencing was used to assay the effect of mifepristone treatment on gene expression in adult Drosophila, including males, virgin females and mated females. Overall design: Males of strain w[1118]; p53B[6] were crossed to virgins of w[1118]; rtTA(3)E2 and progeny males and virgins were collected over 48 hours. One half of the virgins were mated to w[1118] males at ratio of 1:1 virgins to males for 4 days. Mated females were then separated from the w[1118] males. The mated females, males and virgins females were then maintained at approximately 20 flies per vial, on food with and without supplementation with 160ug/ml mifepristone for 12 days. Total fly RNA was isolated from 20 animals per sample. Three replicate samples were generated for each type of flies: males, mated females and virgin females.
The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila.
Specimen part, Subject
View SamplesThe objective of this study is to search for calcium signal-dependent expression changes.
Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury.
Specimen part
View SamplesWe used an Aldefluor assay system to study the signaling pathways that regulate the frequency and maintenance of ALDH-positive cell population in MCF-7 cells as a CSC model.
Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation.
Cell line
View SamplesIt has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) has a common etiological background, but little is known about the linkage al the molecular level.
Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction.
Specimen part, Disease, Disease stage
View SamplesSynovial and bone marrow mesenchymal stem cells after intradiscally injection show regenerative effects of nucleus pulposus.
Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits.
Specimen part
View SamplesOne of strategies to regenerate cartilage defect is transplantation of mesenchymal stem cells (MSCs). Improvements of therapeutic potential of MSCs are needed to achieve successful cartilage regeneration by transplantation of a limited number of cells. Aggregated culture is a popular method in ES and iPS cells to maintain or enhance their potentials. Here we investigated gene expression profile of aggregated MSCs. 621 genes were up-regulated and 409 genes were down-regulated more than 5-fold in MSC-aggregates compared with the number in MSCs in a monolayer culture. The most up-regulated gene was BMP2, which is one of the genes involved in chondrogenesis. Anti-inflammatory genes were also up-regulated in MSC-aggregates. The microarray data for selected genes were confirmed by real-time PCR.
Properties and usefulness of aggregates of synovial mesenchymal stem cells as a source for cartilage regeneration.
Specimen part, Treatment, Subject
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