HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1135v1 56/7/1751    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rong, J. X Articles by Ryan, T. E Search for Related Content PubMed PubMed Citation Articles by Rong, J. X Articles by Ryan, T. E Social Bookmarking                What's this?

ADIPOSE MITOCHONDRIAL BIOGENESIS IS SUPPRESSED IN DB/DB & HIGH-FAT DIET-FED MICE AND IMPROVED BY ROSIGLITAZONE

James X Rong^*, Yang Qiu^,,, Michael K Hansen, Lei Zhu^,, Vivian Zhang, Mi Xie^*, Yuji Okamoto^||, Michael D Mattie^¶, Hiroyuki Higashiyama^||, Satoshi Asano^||, Jay C Strum^¶, and Terence E Ryan

*High Throughput Biology, Discovery Research
Cheminformatics, Discovery Research
Biomedical Data Sciences
^¶Department of Quantitative Expression, Genetics Research, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709
Integrative Biology, High Throughput Biology, Discovery Research, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA19406
^||Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, 43 Wadai, Tsukuba, Ibaraki, Japan 300-4278

Correspondence: james.x.rong{at}gsk.com

Objective:The objective of this study was to further establish and confirm the relationship of adipose mitochondrial biogenesis in diabetes/obesity and the effects of rosiglitazone (RSG), a PPAR agonist, by systematically analyzing mitochondrial gene expression and function in two mouse models of obesity and type II diabetes.

Research Design & Methods:Using microarray technology, adipose mitochondrial gene transcription was studied in db/db, high-fat diet-fed C57BL/6 (HFD), and respective control mice with or without RSG treatment. The findings were extended using mitochondrial staining, DNA quantification, and measurements of citrate synthase activity.

Results:In db/db and HFD mice, gene transcripts associated with mitochondrial ATP production, energy uncoupling, mitochondrial ribosomal proteins, outer and inner membrane translocases, and mitochondrial heat-shock proteins were decreased in abundance, compared to db/+ and standard-fat diet-fed control mice, respectively. RSG dose-dependently increased these transcripts in both db/db and HFD mice, and induced transcription of mitochondrial structural proteins and cellular antioxidant enzymes, responsible for removal of reactive oxygen species generated by increased mitochondrial activity. Transcription factors, including PGC1ß, PGC1, ERR and PPAR, were suppressed in both models and induced by RSG. The effects of RSG on adipose mitochondrial genes were confirmed by quantitative RT-PCR, and further supported by mitochondrial staining, mitochondrial DNA quantification, and citrate synthase activity.

Conclusions:Adipose mitochondrial biogenesis was overwhelmingly suppressed in both mouse models of diabetes/obesity and globally induced by RSG. These findings suggest an important role of adipose mitochondria in diabetes/obesity, and the potential for new treatment approaches targeting adipose mitochondria.

CiteULike

Del.icio.us

Digg

Reddit

Technorati