Rosiglitazone induces mitochondrial biogenesis in mouse brain.
Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain in an apolipoprotein (Apo) E isozyme-independent manner. Rosiglitazone induced both mitochondrial DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of mitochondrial biogenesis. Transcriptomics and proteomics analysis suggested the mitochondria produced in the presence of human ApoE3 and E4 were not as metabolically efficient as those in the wild type or ApoE knockout mice. Thus, we propose that PPARgamma agonism induces neuronal mitochondrial biogenesis and improves glucose utilization leading to improved cellular function and provides mechanistic support for the improvement in cognition observed in treatment of Alzheimer's patients with rosiglitazone.
Strum
Jay C
JC
Department of Quantitative Expression, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC 27278, USA. Jay.C.Strum@gsk.com
Shehee
Ron
R
Virley
David
D
Richardson
Jill
J
Mattie
Michael
M
Selley
Paula
P
Ghosh
Sujoy
S
Nock
Christina
C
Saunders
Ann
A
Roses
Allen
A
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D053318:Apolipoprotein E3 / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics*; D005625:Frontal Lobe / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects*; D001678:Organelle Biogenesis; D047495:PPAR gamma / Q000819:agonists; D012333:RNA, Messenger / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D000097983:ERRalpha Estrogen-Related Receptor
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004272:DNA, Mitochondrial; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D000097983:ERRalpha Estrogen-Related Receptor