title: Impaired exercise-induced mitochondrial biogenesis in the obese Zucker rat, despite PGC-1α induction, is due to compromised mitochondrial translation elongation.
abstract: Previously, we demonstrated that high-volume resistance exercise stimulates mitochondrial protein synthesis (a measure of mitochondrial biogenesis) in lean but not obese Zucker rats. Here, we examined factors involved in regulating mitochondrial biogenesis in the same animals. PGC-1α was 45% higher following exercise in obese but not lean animals compared with sedentary counterparts. Interestingly, exercised animals demonstrated greater PPARδ protein in both lean (47%) and obese (>200%) animals. AMPK phosphorylation (300%) and CPT-I protein (30%) were elevated by exercise in lean animals only, indicating improved substrate availability/flux. These findings suggest that, despite PGC-1α induction, obese animals were resistant to exercise-induced synthesis of new mitochondrial and oxidative protein. Previously, we reported that most anabolic processes are upregulated in these same obese animals regardless of exercise, so the purpose of this study was to assess specific factors associated with the mitochondrial genome as possible culprits for impaired mitochondrial biogenesis. Exercise resulted in higher mRNA contents of mitochondrial transcription factor A (∼50% in each phenotype) and mitochondrial translation initiation factor 2 (31 and 47% in lean and obese, respectively). However, mitochondrial translation elongation factor-Tu mRNA was higher following exercise in lean animals only (40%), suggesting aberrant regulation of mitochondrial translation elongation as a possible culprit in impaired mitochondrial biogenesis following exercise with obesity.
authors.affiliation: Applied Exercise Science Laboratory, Department of Health and Kinesiology, Texas A & M University, College Station, Texas;
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Greene
authors.forename: Mats I
authors.initials: MI
authors.lastname: Nilsson
authors.forename: Tyrone A
authors.initials: TA
authors.lastname: Washington
authors.forename: David E
authors.initials: DE
authors.lastname: Lee
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Brown
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Papineau
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Shimkus
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Greene
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Crouse
authors.forename: James D
authors.initials: JD
authors.lastname: Fluckey
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000502:physiology*; D063269:Mitochondrial Turnover / Q000502:physiology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047494:PPAR delta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases
keywords: mitochondrial protein synthesis; mitochondrial transcription and translation; oxidative metabolism; peroxisome proliferator-activated receptor-γ coactivator-1α