Transcriptomics

Dataset Information

0

Liver-specific knockdown of JNK1


ABSTRACT: Liver-specific Knockdown of JNK1 Up-regulates Proliferator-activated Receptor Coactivator 1 and Increases Plasma Triglyceride despite Reduced Glucose and Insulin Levels in Diet-induced Obese Mice. The c-Jun N-terminal kinases (JNKs) have been implicated in the development of insulin resistance, diabetes, and obesity. Genetic disruption of JNK1, but not JNK2, improves insulin sensitivity in diet-induced obese (DIO) mice. We applied RNA interference to investigate the specific role of hepatic JNK1 in contributing to insulin resistance in DIO mice. Adenovirus-mediated delivery of JNK1 short-hairpin RNA (Ad-shJNK1) resulted in almost complete knockdown of hepatic JNK1 protein without affecting JNK1 protein in other tissues. Liver-specific knockdown of JNK1 resulted in significant reductions in circulating insulin and glucose levels, by 57 and 16%, respectively. At the molecular level, JNK1 knockdown mice had sustained and significant increase of hepatic Akt phosphorylation. Furthermore, knockdown of JNK1 enhanced insulin signaling in vitro. Unexpectedly, plasma triglyceride levels were robustly elevated upon hepatic JNK1 knockdown. Concomitantly, expression of proliferator-activated receptor coactivator 1, glucokinase, and microsomal triacylglycerol transfer protein was increased. Further gene expression analysis demonstrated that knockdown of JNK1 up-regulates the hepatic expression of clusters of genes in glycolysis and several genes in triglyceride synthesis pathways. Our results demonstrate that liver-specific knockdown of JNK1 lowers circulating glucose and insulin levels but increases triglyceride levels in DIO mice. Keywords: Treatment Response

ORGANISM(S): Mus musculus

PROVIDER: GSE7648 | GEO | 2007/10/02

SECONDARY ACCESSION(S): PRJNA99767

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2008-06-15 | E-GEOD-7648 | biostudies-arrayexpress
2019-12-27 | GSE124929 | GEO
2018-10-04 | PXD010212 | Pride
2016-06-29 | E-GEOD-79008 | biostudies-arrayexpress
2014-08-20 | E-GEOD-60527 | biostudies-arrayexpress
2016-06-29 | GSE79008 | GEO
2014-08-20 | GSE60527 | GEO
2009-11-25 | GSE19185 | GEO
2021-08-11 | GSE144414 | GEO
2020-04-14 | GSE143319 | GEO