Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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: Alessandro Provenzani

PROVIDER: E-GEOD-73759 | biostudies-arrayexpress |

REPOSITORIES: biostudies-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]

PMID: 27230858

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Project description:An 8-week high fat palm oil diet causes obesity and insulin resistance in C57BL/6J mice, but induces only small changes in the muscle transcriptome. Introduction: The metabolic syndrome (MS) is a cluster of metabolic abnormalities linked to an increased risk of type 2 diabetes and cardiovascular diseases. Two major characteristics of the MS are obesity and insulin resistance. In the present study we investigated the effect of obesity and insulin resistance on the mouse muscle transcriptome. Methods: C57BL/6J mice were fed a palm oil-based low fat diet (LFD) or high fat diet (HFD) for eight weeks. Microarray analysis was performed by using two complementary strategies: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. Results: HFD mice develop obesity and whole-body insulin resistance. Despite these metabolic disturbances we found that HFD induces relatively small changes in gene expression (< 1.3 fold). Only the up-regulation of FA oxidation and the down-regulation of the MAPK cascade were specific for the HFD intervention. Eight-weeks of aging induced more changed gene expression levels than the HFD, including genes involved in cell-cell interaction and development. Conclusion: Eight weeks of aging induce more pronounced changes in the muscle transcriptome than an HFD. Since only one strategy revealed the transcriptional down-regulation of the MAPK cascade, whereas both strategies showed the up-regulation of FA oxidation we suggest the use of complementary analysis strategies by the genome-wide search of gene expression changes induced by mild interventions, such as an HFD. Keywords: diet intervention and time course In this study, C57BL/6J mice were fed a high fat (HF) diet for 8 weeks to induce obesity and insulin resistance. Plasma levels of the adipokines leptin and adiponectin were measured. To investigate how these metabolic disturbances will influence the skeletal muscle transcriptome we performed whole-genome microarray analysis. Functional implications were assessed by analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways.

Dataset Information

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

Publications

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

Similar Datasets

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