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Voluntary wheel running is necessary for hepatic PGC‐1α adenovirus overexpression to increase hepatic mitochondria in LCR rats (LB741)
Author(s) -
Meers Grace,
Morris E. Matthew,
Koch Lauren,
Britton Steve,
Thyfault John
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb741
Subject(s) - citrate synthase , medicine , endocrinology , coactivator , messenger rna , mitochondrion , sed , sirt3 , peroxisome proliferator activated receptor , receptor , biology , chemistry , biochemistry , gene , nad+ kinase , transcription factor , enzyme , sirtuin
The hepatic adenoviral overexpression (o/e) of peroxisome proliferator‐activated receptor‐γ coactivator‐1α adenovirus (PGC‐1α) in sedentary (SED) low capacity running (LCR) rats increases PGC‐1α mRNA, but does not induce increased PGC‐1α protein, increased mitochondrial content or fatty acid oxidation, as we have previously observed in SED Sprague‐Dawley rats. It is well known that PGC‐1α expression is highly regulated post‐transcriptionally leading us to believe that LCR possess an unknown “brake” that blocks the impact of increased PGC‐1α mRNA. We hypothesized that increased energy expenditure via voluntary wheel running (VWR) would result in increased hepatic PGC‐1α protein in the LCR following PGC‐1α o/e. LCR rats (age=20 wks; n=4‐8) were assigned to SED+PGC‐1α or VWR+PGC‐1α for 4 weeks while β‐galactosidase adenovirus groups served as controls. VWR reduced fat pad mass (~ 50%; p<0.05) but not body mass compared to SED. Both the SED+PGC‐1α and the VWR+PGC‐1α increased hepatic PGC‐1α mRNA, but only the VWR group displayed increased citrate synthase activity and complete palmitate oxidation (p<0.05). The lack of an increase in PGC‐1α protein and mitochondrial function following PGC‐1α o/e cannot be explained by known regulators of PGC‐1α transcriptional activity, SIRT3 or GCN5, as they did not differ between groups. The micro RNA, MiR‐23A, is known to lower PGC‐1α mRNA and protein content in muscle. We observed that MiR‐23A was unexpectedly higher in VWR vs. SED suggesting that this was also not a brake on PGC‐1α function. In conclusion, hepatic adenoviral o/e of PGC‐1α only increases mitochondrial function in running but not SED LCR rats, and the improved function is independent of increased PGC‐1α protein content. Grant Funding Source : Supported by: NIH DK‐088940, NIH T32 AR‐048523, and HSTMVA resources and facilities