Unknown,Transcriptomics,Genomics,Proteomics

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Comprehensive analysis of different in vitro insulin resistance models


ABSTRACT: Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-a, hypoxia, dexamethasone, high insulin, and a combination of TNF-a and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNF-a and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we further examined the transcriptional regulation of TNF-a-induced insulin resistance, and we found that C/EPBM-CM-^_ key regulator of adipose insulin resistance. RNA-seq for 6 insulin resistance conditions and 2 control conditions, Dnase hypersensitivity-seq of 4 conditions and 1 control condition, ChIP-seq on p65 after TNFa treatment.

ORGANISM(S): Mus musculus

SUBMITTER: Kinyui Alice LO 

PROVIDER: E-GEOD-35724 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Analysis of in vitro insulin-resistance models and their physiological relevance to in vivo diet-induced adipose insulin resistance.

Lo Kinyui Alice KA   Labadorf Adam A   Kennedy Norman J NJ   Han Myoung Sook MS   Yap Yoon Sing YS   Matthews Bryan B   Xin Xiaofeng X   Sun Lei L   Davis Roger J RJ   Lodish Harvey F HF   Fraenkel Ernest E  

Cell reports 20131003 1


Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-α, hypoxia, dexamethasone, high insulin, and a combination of TNF-α and hypoxia, comparing the results to the changes in white adipose  ...[more]

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