Transcriptomics

Dataset Information

6

Nuclear receptor, RORa plays a critical role in obesity-associated inflammation, hepatic steatosis, and insulin resistance


ABSTRACT: We demonstrated that RORa-deficient staggerer mice (RORasg/sg) fed with a high fat diet (HFD) showed reduced adiposity and hepatic triglyceride levels compared to wild type (WT) littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance. Gene expression profiling showed that many genes involved in triglyceride synthesis and storage, including Cidec, Cidea, and Mogat1, were expressed at much lower levels in liver of RORasg/sg mice. In addition to reduced lipid accumulation, inflammation was greatly diminished in white adipose tissue (WAT) of RORasg/sg mice fed with a HFD. The infiltration of macrophages and the expression of many immune-response and pro-inflammatory genes, including those encoding various chemo/cytokines, toll-like receptors, and TNF signaling proteins, were significantly reduced in RORasg/sg WAT. Moreover, RORasg/sg mice fed with a HFD were protected from the development of insulin resistance. Together, these results indicate that RORa plays a critical role in the regulation of several aspects of metabolic syndrome. Therefore, RORa may provide a novel therapeutic target in the management of obesity and associated metabolic diseases. Liver and white adipose tissue (WAT) total RNAs were purified from 5 WT and 5 RORasg/sg (natural deletion of RORa gene in mice) mice fed with a high fat diet for 6 weeks. Then samples were applied on Agilent mouse genome chip.

ORGANISM(S): Mus musculus  

SUBMITTER: Anton M Jetten   Kyoko Okamoto  HongSoon Kang  NIEHS Microarray Core 

PROVIDER: E-GEOD-23736 | ArrayExpress | 2011-04-30

SECONDARY ACCESSION(S): GSE23736PRJNA130775

REPOSITORIES: GEO, ArrayExpress

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Publications

Transcriptional profiling reveals a role for RORalpha in regulating gene expression in obesity-associated inflammation and hepatic steatosis.

Kang Hong Soon HS   Okamoto Kyoko K   Takeda Yukimasa Y   Beak Ju Youn JY   Gerrish Kevin K   Bortner Carl D CD   DeGraff Laura M LM   Wada Taira T   Xie Wen W   Jetten Anton M AM  

Physiological genomics 20110503 13


Retinoid-related orphan receptor (ROR)α4 is the major RORα isoform expressed in adipose tissues and liver. In this study we demonstrate that RORα-deficient staggerer mice (RORα(sg/sg)) fed with a high-fat diet (HFD) exhibited reduced adiposity and hepatic triglyceride levels compared with wild-type (WT) littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance. Gene expression profiling showed that many genes involved in trigl  ...[more]

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