Transcriptomics

Dataset Information

3

JNK1 Ablation in Mice Confers Long-term Metabolic Protection from Diet-Induced Obesity at the Cost of Increased Skin Oxidative Damage


ABSTRACT: Obesity and insulin resistance are associated with oxidative stress, which may be implicated in their progression. The kinase JNK1 emerged as a promising drug target for the treatment of obesity and type-2 diabetes. However, JNK1 is a key mediator of the oxidative stress response, promoting either cell dead or survival depending on magnitude and context of its activation. Furthermore, JNK inactivation shortens lifespan in drosophila and c. elegans. To learn on the safety and efficacy of long-term JNK inhibition in vertebrates, we investigated mice lacking JNK1 (JNK1-/-) exposed over a long period to an obesogenic high-fat diet (HFD). JNK1-/- mice chronically fed an HFD developed more skin oxidative damage because of reduced catalase expression, but also showed sustained protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, paralleled by decreased oxidative damage in fat and liver. We conclude that JNK1 is a relatively safe drug target for obesity-related diseases. RNA was collected from liver, skin and epididymal fat tissues from JNK1 KO mice and WT mice fed in high fat diet. Each condition was run in quadruplicate

ORGANISM(S): Mus musculus  

SUBMITTER: Tarcisio Fedrizzi   Barbara Becattini  Min-Kyung Choo  Giovanni Solinas  Vito G D'Agostino  Ludovic Breasson  Alessandro Provenzani  Jin M Park  Michael Pancher  Fabio Zani  Lucia Radici 

PROVIDER: E-GEOD-73759 | ArrayExpress | 2016-09-01

SECONDARY ACCESSION(S): GSE73759PRJNA297836

REPOSITORIES: GEO, ArrayExpress

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Publications

JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage.

Becattini Barbara B   Zani Fabio F   Breasson Ludovic L   Sardi Claudia C   D'Agostino Vito Giuseppe VG   Choo Min-Kyung MK   Provenzani Alessandro A   Park Jin Mo JM   Solinas Giovanni G  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20160526 9


Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its activation. In this article, we describe a study in which the long-term effects of JNK1 inactivation on  ...[more]

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