Training at low intensities with moderate vascular occlusion results in increased muscle hypertrophy, strength, and endurance. Elastic knee wraps, applied to the proximal portion of the target muscle, might elicit a stimulus similar to the KAATSU Master Apparatus. The purpose of this study was to test the hypothesis that intermittently occluding the leg extensors with elastic knee wraps would increase whole-blood lactate (WBL) over control (CON). Twelve healthy men and women participated in this study (age 21.2 ± 0.35 years, height 168.9 ± 2.60 cm, and body mass 71.2 ± 4.16 kg). One repetition maximum (1RM) testing for the leg extensors was performed on a leg extension machine for the first trial, followed by occlusion (OCC) and CON trials. Four sets of leg extension exercise (30-15-15-15) were completed with 150-second rest between sets at 30% 1RM. Whole-blood lactate, heart rate (HR), and ratings of perceived exertion (RPEs) were measured after every set of exercise and 3 minutes postexercise. Data were analyzed using repeated-measures analysis of variance with statistical significance set at p ≤ 0.05. Whole-blood lactate increased in response to exercise (p = 0.01) but was not different between groups (OCC 6.28 ± 0.66 vs. CON 5.35 ± 0.36 mmol·L, p = 0.051). Heart rate (OCC 128.86 ± 4.37 vs. CON 119.72 ± 4.10 b·min⁻¹) was higher with OCC from sets 2-4 (p ≤ 0.03), with no difference 3 minutes postexercise (p = 0.29). Rating of perceived exertion was higher with OCC after every set (OCC 15.10 ± 0.31 vs. CON 12.16 ± 0.50, p = 0.01). In conclusion, no differences exist for WBL between groups, although there was a trend for higher levels with OCC. The current protocol for practical occlusion did not significantly increase metabolic stress more than normal low-intensity exercise. This study does not support the use of knee wraps as a mode of blood-flow restriction.

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.

Thyfault JP, Rector RS. Combining metformin and aerobic exercise training in the treatment of type 2 diabetes and NAFLD in OLETF rats. Am J Physiol Endocrinol Metab 306: E300 -E310, 2014. First published December 10, 2013; doi:10.1152/ajpendo.00427.2013.-Here, we sought to compare the efficacy of combining exercise and metformin for the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in hyperphagic, obese, type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats (age: 20 wk, hyperglycemic and hyperinsulinemic; n ϭ 10/group) were randomly assigned to sedentary (O-SED), SED plus metformin (O-SED ϩ M; 300 mg·kg Ϫ1 ·day Ϫ1 ), moderate-intensity exercise training (O-EndEx; 20 m/min, 60 min/day, 5 days/wk treadmill running), or O-EndEx ϩ M groups for 12 wk. Long-Evans Tokushima Otsuka (L-SED) rats served as nonhyperphagic controls. O-SED ϩ M, O-EndEx, and O-EndEx ϩ M were effective in the management of type 2 diabetes, and all three treatments lowered hepatic steatosis and serum markers of liver injury; however, O-EndEx lowered liver triglyceride content and fasting hyperglycemia more than O-SED ϩ M. In addition, exercise elicited greater improvements compared with metformin alone on postchallenge glycemic control, liver diacylglycerol content, hepatic mitochondrial palmitate oxidation, citrate synthase, and ␤-HAD activities and in the attenuation of markers of hepatic fatty acid uptake and de novo fatty acid synthesis. Surprisingly, combining metformin and aerobic exercise training offered little added benefit to these outcomes, and in fact, metformin actually blunted exerciseinduced increases in complete mitochondrial palmitate oxidation and ␤-HAD activity. In conclusion, aerobic exercise training was more effective than metformin administration in the management of type 2 diabetes and NAFLD outcomes in obese hyperphagic OLETF rats. Combining therapies offered little additional benefit beyond exercise alone, and findings suggest that metformin potentially impairs exercise-induced hepatic mitochondrial adaptations. exercise training; metformin; nonalcoholic fatty liver disease; hepatic mitochondria; de novo lipogenesis; Otsuka Long-Evans Tokushima Fatty rats NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) is a progressive liver disease characterized by hepatic triglyceride (TG) accumulation (Ն5% by weight for diagnosis) that occurs in the absence of excess alcohol consumption (Ͼ20 g/day). It encompasses a histological spectrum ranging from simple hepatic steatosis to nonalcoholic steatohepatitis, advanced fibrosis, and cirrhosis (40). NAFLD is considered the hepatic manifestation of the metabolic syndrome (11), and it affects ϳ30% of the US adult population (3, 7) and ϳ70% of type 2 diabetics (52). However, there are currently no clear guidelines for the treatment of NAFLD.A component of prevention and treatment recommendations addressing NAFLD involves lifestyle modifications that alter net energy status. Indeed, both short-term (6) and longer-term caloric restriction (10, 23), a...

PURPOSE Elevated postprandial glycemic excursions (PPG) are significant risk factors for cardiovascular disease in type 2 diabetes patients. Here we tested if and for how many meals a single bout of exercise would reduce PPG responses to subsequent meals in type 2 diabetes (T2D) patients using continuous glucose monitors (CGMS). METHODS We recruited 9 sedentary (<30 minutes/week of exercise) individuals with T2D (BMI: 36.0 ± 1.1 kg/m2; age 60.3 ± 1.0 years; HbA1c: 6.3 ± 0.2 %). The subjects consumed a eucaloric diet (51% carbohydrate, 31% fat, 18% protein) consisting of 3 meals, identical in composition, over a 2-day period while wearing CGMS in two different conditions (exercise (EX; one 60 minute bout at 60-75% of heart rate reserve performed prior to breakfast) vs. a sedentary (SED) condition). We quantified 24-h average glucose, PPG-AUC (4 h glucose AUC following meals) and PPG-2 h (2 hour post-prandial glucose). RESULTS EX significantly reduced average [glucose] during the first 24 hour period (p=0.03). EX caused a reduction in PPG-AUC (p=0.02) for all of the meals over the two days (main effect between conditions). Comparison between the EX and SED conditions at each meal revealed that EX reduced PPG-AUC following the second meal of day 1 (lunch) (p=0.04). PPG-2 h was not significantly different between EX and SED. CONCLUSION Although a single EX bout does lower 24-h average [glucose], it only significantly lowered PPG-AUC at the second meal following the bout suggesting that daily exercise may be needed to most effectively improve PPG at the advent of exercise training in T2D patients.