Decreased pancreatic amylase activity after acute high-intensity exercise and its effects on post-exercise muscle glycogen recovery.

Our prior results showed that an acute bout of endurance exercise for 6 h, but not 1 h, decreased pancreatic amylase activity, indicating that acute endurance exercise may affect carbohydrate digestive capacity in an exercise duration-dependent manner. Here, we investigated the effects of acute endurance exercise of different intensities on mouse pancreatic amylase activity. Male C57BL/6J mice performed low- or high-intensity running exercise for 60 min at either 10 (Ex-Low group) or 20 m/min (Ex-High group). The control group comprised sedentary mice. Immediately after acute exercise, pancreatic amylase activity was significantly decreased in the Ex-High group and not the Ex-Low group in comparison with the control group. To determine whether the decreased amylase activity induced by high-intensity exercise influenced muscle glycogen recovery after exercise, we investigated the rates of muscle glycogen resynthesis in Ex-High group mice administered either oral glucose or starch solution (2.0 mg/g body weight) immediately after exercise. The starch-fed mice exhibited significantly lower post-exercise glycogen accumulation rates in the 2-h recovery period compared with the glucose-fed mice. This difference in the glycogen accumulation rate was absent for starch- and glucose-fed mice in the sedentary (no exercise) control group. Furthermore, the plasma glucose AUC during early post-exercise recovery (0-60 min) was significantly lower in the starch-fed mice than in the glucose-fed mice. Thus, our findings suggest that acute endurance exercise diminishes the carbohydrate digestive capacity of the pancreas in a manner dependent on exercise intensity, with polysaccharides leading to delayed muscle glycogen recovery after exercise.

PGC-1α activation boosts exercise-dependent cellular response in the skeletal muscle.

The role of Peroxisome proliferator-activated receptor-gamma coactivator alpha (PGC-1α) in fat metabolism is not well known. In this study, we compared the mechanisms of muscle-specific PGC-1α overexpression and exercise-related adaptation-dependent fat metabolism. PGC-1α trained (PGC-1α Ex) and wild-trained (wt-ex) mice were trained for 10 weeks, five times a week at 30 min per day with 60 percent of their maximal running capacity. The PGC-1α overexpressed animals exhibited higher levels of Fibronectin type III domain-containing protein 5 (FNDC5), 5' adenosine monophosphate-activated protein kinase alpha (AMPK-α), the mammalian target of rapamycin (mTOR), Sirtuin 1 (SIRT1), Lon protease homolog 1 (LONP1), citrate synthase (CS), succinate dehydrogenase complex flavoprotein subunit A (SDHA), Mitofusin-1 (Mfn1), endothelial nitric oxide synthase (eNOS), Hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), G protein-coupled receptor 41 (GPR41), and Phosphatidylcholine Cytidylyltransferase 2 (PCYT2), and lower levels of Sirtuin 3 (SIRT3) compared to wild-type animals. Exercise training increased the protein content levels of SIRT1, HSL, and ATGL in both the wt-ex and PGC-1α trained groups. PGC-1α has a complex role in cellular signaling, including the upregulation of lipid metabolism-associated proteins. Our data reveals that although exercise training mimics the effects of PGC-1α overexpression, it incorporates some PGC-1α-independent adaptive mechanisms in fat uptake and cell signaling.

The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice.

Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits of lactate, the by-product of exercise, in various aspects of brain function and disorders. However, there remains a gap in understanding the effects of lactate dosage and its impact on aged rodents. The present study first examined the long-term effects of three different doses of lactate intervention (2000 mg/kg, 1000 mg/kg, and 500 mg/kg) and high-intensity interval training (HIIT) on aging mice (20-22 months) as the 1st experiment. Subsequently, in the 2nd experiment, we investigated the long-term effects of 500 mg/kg lactate intervention and HIIT on brain neuroplasticity in aged mice (25-27 months). The results of the 1st experiment demonstrated that both HIIT and different doses of lactate intervention (500 mg/kg and 2000 mg/kg) positively impacted the neuroplasticity biomarker VEGF in the hippocampus of aging mice. Subsequently, the 2nd experiment revealed that long-term HIIT significantly improved the performance of mice in open-field, novel object recognition, and passive avoidance tests. However, lactate intervention did not significantly affect these behavioral tests. Moreover, compared to the control group, both HIIT and lactate intervention positively influenced the angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial biomarker (SDHA), and metabolic protein (p/t-CREB, p/t-HSL, and LDH) in the hippocampus of aged mice. Notably, only lactate intervention significantly elevated the BDNF (PGC-1α, SIRT1, and BDNF) signaling pathway and metabolic content (lactate and pyruvate). In the end, long-term HIIT and lactate intervention failed to change the protein expression of p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 and Pan Lactic aid-Lysine in the hippocampus of aged mice. In summary, the present study proved that long-term HIIT and lactate treatment have positive effects on the brain functions of aged mice, suggesting the potential usage of lactate as a therapeutic strategy in neurodegenerative diseases in the elderly population.

A very high-carbohydrate diet differentially affects whole-body glucose tolerance and hepatic insulin resistance in rats.

OBJECTIVES: This study was performed to assess the effects of long-term intake of a very high carbohydrate (VHCHO) diet (76% of total energy from carbohydrate [CHO]) on whole-body glucose tolerance and hepatic insulin resistance. METHODS AND MATERIALS: Male Sprague Dawley rats were fed either a control high-CHO diet (59% total energy from CHO; n = 8) or a VHCHO diet (76% total energy from CHO; n = 8) for 17 wk. At 4, 8, 12, and 16 wk of the dietary intervention, oral glucose tolerance test and homeostasis model assessment of insulin resistance (HOMA-IR) measurements were taken to assess whole-body glucose tolerance and hepatic insulin resistance, respectively. The triacylglycerol concentration in the liver was measured at the end of the 17-wk intervention period. RESULTS: The VHCHO diet group showed significantly higher muscle glucose transporter 4 content and a smaller area under the curve for plasma glucose, but not insulin, in the oral glucose tolerance test compared with the control group. On the other hand, the VHCHO diet group had a significantly higher hepatic triacylglycerol concentration and HOMA-IR measurement compared with the control group. The hepatic triacylglycerol concentration was significantly and positively correlated with HOMA-IR. CONCLUSIONS: The results of the present study suggest that long-term intake of a VHCHO diet exerts differential effects on whole-body glucose tolerance and hepatic insulin resistance.

Long-term iron supplementation combined with vitamin B6 enhances maximal oxygen uptake and promotes skeletal muscle-specific mitochondrial biogenesis in rats.

Introduction: Iron is an essential micronutrient that plays a crucial role in various biological processes. Previous studies have shown that iron supplementation is related to exercise performance and endurance capacity improvements. However, the underlying mechanisms responsible for these effects are not well understood. Recent studies have suggested the beneficial impact of iron supplementation on mitochondrial function and its ability to rescue mitochondrial function under adverse stress in vitro and rodents. Based on current knowledge, our study aimed to investigate whether the changes in exercise performance resulting from iron supplementation are associated with its effect on mitochondrial function. Methods: In this study, we orally administered an iron-based supplement to rats for 30 consecutive days at a dosage of 0.66 mg iron/kg body weight and vitamin B6 at a dosage of 0.46 mg/kg. Results: Our findings reveal that long-term iron supplementation, in combination with vitamin B6, led to less body weight gained and increased VO2 max in rats. Besides, the treatment substantially increased Complex I- and Complex II-driven ATP production in intact mitochondria isolated from gastrocnemius and cerebellum. However, the treatment did not change basal and succinate-induced ROS production in mitochondria from the cerebellum and skeletal muscle. Furthermore, the iron intervention significantly upregulated several skeletal muscle mitochondrial biogenesis and metabolism-related biomarkers, including PGC-1α, SIRT1, NRF-2, SDHA, HSL, MTOR, and LON-P. However, it did not affect the muscular protein expression of SIRT3, FNDC5, LDH, FIS1, MFN1, eNOS, and nNOS. Interestingly, the iron intervention did not exert similar effects on the hippocampus of rats. Discussion: In conclusion, our study demonstrates that long-term iron supplementation, in combination with vitamin B6, increases VO2 max, possibly through its positive role in regulating skeletal muscle-specific mitochondrial biogenesis and energy production in rats.

Effects of a Very High-Carbohydrate Diet and Endurance Exercise Training on Pancreatic Amylase Activity and Intestinal Glucose Transporter Content in Rats.

We previously reported that the combination of a very high-carbohydrate diet and endurance training increased glucose transporter 4 and glycogen concentration in skeletal muscle. However, it remains unclear whether they also affect the digestive and absorptive capacity in the pancreas and small intestine, which are suggested to be rate-limiting steps in the delivery of exogenous carbohydrates to skeletal muscle and muscle glycogen synthesis. Thus, we aimed to evaluate the effects of a very high-carbohydrate diet and endurance training on pancreatic amylase activity and intestinal glucose transporters in rats and to examine the relationship between these adaptations and their influence on muscle glycogen concentration. Male Sprague-Dawley rats (n=29) were fed a high-carbohydrate diet (59% carbohydrate) or a very high-carbohydrate diet (76% carbohydrate) for 4 wk. Half of the rats in each dietary group were subjected to 6-h swimming exercise training (two 3-h sessions separated by 45 min of rest) for 4 wk. Although there was no significant effect of diet or endurance training on sodium-dependent glucose transporter 1 and glucose transporter 2 contents in the intestine, the rats fed a very high-carbohydrate diet in combination with endurance training had substantially higher pancreatic amylase activity and muscle glycogen concentration. Furthermore, there was a positive correlation between pancreatic amylase activity and muscle glycogen concentration (r=0.599, p=0.001). In conclusion, intake of a very high-carbohydrate diet and endurance training synergistically elevated carbohydrate digestive capacity, which partially accounted for the higher muscle glycogen accumulation.

Effects of Dietary Fat Restriction on Endurance Training-induced Metabolic Adaptations in Rat Skeletal Muscle.

Endurance exercise training enhances muscle fat oxidation while concomitantly reducing carbohydrate (glycogen) utilization during exercise, thereby delaying the onset of fatigue. This study examined the effects of dietary fat restriction on endurance training-induced metabolic adaptations in rat skeletal muscle. Male Sprague-Dawley rats were placed on either a control diet (CON: 19.2% protein, 21.6% fat, and 59.2% carbohydrate as a percentage of total energy) or a fat-restricted diet (FR: 21.5% protein, 2.4% fat, and 76.1% carbohydrate as a percentage of total energy) for 4 wks. Half the rats in each dietary group performed daily 6-h swimming exercise (two 3-h sessions separated by 45 min of rest) on 5 days each wk. Endurance training significantly increased the expression of ß-hydroxyacyl CoA dehydrogenase (ßHAD), a key enzyme of fat oxidation, and pyruvate dehydrogenase kinase 4 (PDK4), an inhibitory regulator of glycolytic flux, in the skeletal muscle of rats fed the CON diet. However, such endurance training-induced increases in muscle ßHAD and PDK4 were partially suppressed by the FR diet, suggesting that a FR diet may diminish the endurance training-induced enhancement of fat oxidation and reduction in glycogen utilization during exercise. We then assessed the muscle glycogen utilization rate during an acute bout of swimming exercise in the trained rats fed either the CON or the FR diet and consequently found that rats fed the FR diet had a significantly higher muscle glycogen utilization rate during exercise compared with rats fed the CON diet. In conclusion, dietary fat restriction may attenuate the endurance training-induced metabolic adaptations in skeletal muscle.

Effects of a Ketogenic Diet Containing Medium-Chain Triglycerides and Endurance Training on Metabolic Enzyme Adaptations in Rat Skeletal Muscle.

Long-term intake of a ketogenic diet enhances utilization of ketone bodies, a particularly energy-efficient substrate, during exercise. However, physiological adaptation to an extremely low-carbohydrate diet has been shown to upregulate pyruvate dehydrogenase kinase 4 (PDK4, a negative regulator of glycolytic flux) content in skeletal muscle, resulting in impaired high-intensity exercise capacity. This study aimed to examine the effects of a long-term ketogenic diet containing medium-chain triglycerides (MCTs) on endurance training-induced adaptations in ketolytic and glycolytic enzymes of rat skeletal muscle. Male Sprague-Dawley rats were placed on either a standard diet (CON), a long-chain triglyceride-containing ketogenic diet (LKD), or an MCT-containing ketogenic diet (MKD). Half the rats in each group performed a 2-h swimming exercise, 5 days a week, for 8 weeks. Endurance training significantly increased 3-oxoacid CoA transferase (OXCT, a ketolytic enzyme) protein content in epitrochlearis muscle tissue, and MKD intake additively enhanced endurance training-induced increases in OXCT protein content. LKD consumption substantially increased muscle PDK4 protein level. However, such PDK4 increases were not observed in the MKD-fed rats. In conclusion, long-term intake of ketogenic diets containing MCTs may additively enhance endurance training-induced increases in ketolytic capacity in skeletal muscle without exerting inhibitory effects on carbohydrate metabolism.