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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.

Tumors create an extracellular pH (pHe) barrier and form an isolated microenvironment roughly 0.5 pH units lower than physiological pH, while the intracellular pH (pHi) is maintained within 0.2 pH units of physiological levels. Reduced tumor pHi is associated with apoptosis, and lowered arterial and tissue pH are seen with heavy exercise.PURPOSETo determine the pHi response of MCF‐7 cells subjected to acidic environments. MCF‐7 cells loaded with BCECF, a pH indicator, were used to create a standard curve of fluorescent ratios at six pH levels. MCF‐7 cells were then subjected to pHe levels of 6.75 and 6.25 at 0, 15, 30, 45, 60, 120, 180, and 1,440 minutes of pHe exposure. Data were referenced to MCF‐7 cells at a physiological pHe of 7.25. A treatment effect was seen at pHe 6.25 (p = 0.0002). Compared to the control, cells subjected to pHe 6.25 for 15, 30, 45, and 1,440 minutes had lower pHi levels (p = 0.0464, p = 0.0002, p = 0.0257, and p = 0.0054, respectively). An interaction of pHe and time (p = 0.0483) on pHi was observed. The pHi values were lower at pHe 6.25 than at pHe 6.75 after 30, 180, and 1,440 minutes of exposure (p = 0.0193, p = 0.0200, and p < 0.0001, respectively). In conclusion, MCF‐7 cells subjected to a pHe of 6.75 maintained their pHi, but a different recovery response was seen at pHe 6.25. A decreased tolerance of lower pH levels may provide a mechanism by which heavy exercise would prove beneficial for breast cancer patients.

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