Impact of Various Exercise Modalities on Hepatic Mitochondrial Function

Abstract

Hepatic mitochondrial adaptations to exercise are largely unknown. PURPOSE Here we sought to determine the effects of various exercise modalities on measures of hepatic mitochondrial function and metabolism. METHODS Male Sprague Dawley rats were randomly assigned (n=8-10 per group) into sedentary (SED), voluntary wheel running (VWR), VWR with food pulled during the dark cycle (VMR-OF), treadmill endurance exercise (TM-END; 30 m/min, 12% gradient, 60 min/d, 5 d/wk), or treadmill interval sprint training (TM-IST; 50 m/min, 12% gradient, 6×2.5 min bouts, 5 d/wk) groups for a 4 week intervention. RESULTS Hepatic mitochondrial state 3 and maximal uncoupled respiration were significantly (p<0.05) increased in all 4 exercise groups compared with SED animals. In addition, hepatic mitochondrial [1-14C] pyruvate oxidation to CO2, an index of pyruvate dehydrogenase (PDH) activity was significantly increased in VWR-OF, TM-END, and TM-IST rats (p<0.05); whereas, exercise-induced increases in [2-14C] pyruvate oxidation and [1-14C] palmitate oxidation to CO2 did not reach statistical significance. Hepatic mitochondrial sirtuin 3 (SIRT3) protein content, which putatively increases activity of mitochondrial proteins, was elevated in the VWR, VWR-OF and TM-END groups (p<0.05). Additionally, only VWR-OF animals experienced increases in hepatic cytochrome c protein content and PEPCK mRNA, while PGC-1α mRNA expression and phospho-CREB protein content was increased in VWR-OF and TM-END groups. CONCLUSION Four weeks of exercise training, regardless of exercise modality, significantly increased hepatic mitochondrial respiration and evoked other unique improvements in mitochondrial metabolism that do not appear to be dependent on increases in mitochondrial content.

Soy compared with milk protein in a Western diet changes fecal microbiota and decreases hepatic steatosis in obese OLETF rats

“…Ileums were also excised (1 inch above ileal-cecal junction) and immediately flash frozen in liquid nitrogen. Hepatic mitochondria were isolated using centrifugation procedures as previously described [13] and re-suspended in buffer MiPO3 (0.5 mM EGTA, 3 mM MgCl 2 ·6 H 2 O, 60 mM K-lactobionate, 20 mM taurine, 10 mM KH 2 PO 4 , 20 mM HEPES, 110 mM sucrose, 1 g·L −1 BSA, 20 mM histidine, 20 µM vitamin E succinate, 3 mM glutathione, 1 µM leupeptine, 2 mM glutamate, 2 mM malate, and 2 mM Mg-ATP).…”

“…Mitochondrial respiration was assessed using high resolution respirometry (Oroboros Oxygraph-2k; Oroboros Instruments, Innsbruck, Austria) as previously described [13]. Briefly isolated mitochondria were loaded into respiration chambers containing buffer MiR05 (100 mM sucrose, 60mM K-lactobionate, 0.5mM EGTA, 3mM MgCl 2 , 20mM taurine, 10mM KH 2 PO 4 , 20mM HEPES, adjusted to pH 7.1 with KOH at 37°C; and 1 g·L −1 fatty acid-free BSA) to assess basal respiration.…”

Voluntary Running Attenuates Metabolic Dysfunction in Ovariectomized Low-Fit Rats

“…Western blotting was conducted as previously referenced (5, 29, 38). The gastrocnemius muscle tissues were pulverized and homogenized by a tissue homogenizer (TissueLyser LT, Qiagen, Valencia, CA) in Triton X-100 buffer containing protease and phosphatase inhibitors.…”

“…Protein bands were quantified via densitometry and individual protein bands were normalized to β-Actin antibody (#4967, Abcam, Cambridge, MA). Oxidative phosphorylation (OX PHOS) complexes were assessed by an antibody containing complex I subunit NDUFB8, complex II-30kDa, complex IV subunit I, and complex V alpha subunit (Abcam, Cambridge, MA) as described previously (5). Total adenosine monophosphate-activated protein kinase (AMPK)-α, pAMPK Thr 172 and pAMPK Ser 485/491 antibodies were purchased from the Cell Signaling (#2532, #2531, and #4185, respectively; Beverly, MA).…”

Sex differences in the regulation of hepatic mitochondrial turnover following physical activity: do males need more quality control than females?

“…Indeed, a potent enhancer of hepatic mitochondrial function is exercise, whereby only a few weeks of voluntary wheel running in rodents increased markers of oxidative capacity (Fletcher et al . ) and protected against hepatic steatosis (Rector & Thyfault, ). However, the mechanisms by which liver mitochondria adaptations to exercise are regulated remains unknown, and the degree to which sex determines mitochondrial respiratory capacities and improvements with exercise are uncharacterized.…”