Validity and Reliability of Kinvent Plates for Assessing Single Leg Static and Dynamic Balance in the Field.

The objective of this study was to validate PLATES for assessing unipodal balance in the field, for example, to monitor ankle instabilities in athletes or patients. PLATES is a pair of lightweight, connected force platforms that measure only vertical forces. In 14 healthy women, we measured ground reaction forces during Single Leg Balance and Single Leg Landing tests, first under laboratory conditions (with PLATES and with a 6-DOF reference force platform), then during a second test session in the field (with PLATES). We found that for these simple unipodal balance tests, PLATES was reliable in the laboratory and in the field: PLATES gives results comparable with those of a reference force platform with 6-DOF for the key variables in the tests (i.e., Mean Velocity of the Center of Pressure and Time to Stabilization). We conclude that health professionals, physical trainers, and researchers can use PLATES to conduct Single Leg Balance and Single Leg Landing tests in the laboratory and in the field.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

KEY POINTS: Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. ABSTRACT: Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats.

Comparison of oxygen consumption in rats during uphill (concentric) and downhill (eccentric) treadmill exercise tests.

The study of the physiological adaptations of skeletal muscle in response to eccentric (ECC) contraction is based on protocols in which exercise intensities are determined relative to the concentric (CON) reference exercise (as percentage of the CON maximal oxygen consumption, or VO2max). In order to use similar exercise protocols in rats, we compared the VO2 values during uphill (CON) and downhill (ECC) running tests. VO2 was measured in 15 Wistar rats during incremental treadmill running exercises with different slopes: level (0%), positive (+15% incline: CON+15%) and negative (i15% incline: ECC-15%; and 130% incline: ECC-30%). Similar VO2 values were obtained in the ECC-30% and CON+15% running conditions at the three target speeds (15, 25 and 35 cm/sec). Conversely, VO2 values were lower (p < 0.05) in the ECC-15% than in the CON+15% condition (CON+15% VO2/ECC-15% VO2 ratios ranging from 1.86 to 2.05 at the three target speeds). Thus, doubling the downhill slope gradient in ECC condition leads to an oxygen consumption level that is not significantly different as in CON condition. These findings can be useful for designing animal research protocols to study the effects of ECC and CON exercise in ageing population or subjects suffering from cardiovascular diseases. Key PointsVO2 in rats during treadmill race in eccentric and concentric conditions were measured.A novel breath-by-breath device allowing direct access to the animal was used.THREE DIFFERENT SLOPES: +15%, -15% and -30% were used.VO2 values obtained in the -30% eccentric and the +15% concentric conditions were not significantly different.

Neuregulin 1 treatment improves glucose tolerance in diabetic db/db mice, but not in healthy mice.

Context: Neuregulin 1 (NRG1) and ErbB receptors are involved in glucose homeostasis. However, the effects of the neuregulin 1-ErbB pathway activation on glucose metabolism in liver are controversial.Objective: Assess NRG1 and ErbB signalling in liver and the effects of 8-week treatment with NRG1 on glucose homeostasis in diabetic db/db mice and in control healthy mice.Results: NRG1 improved glucose, insulin and insulin sensitivity index during OGTT in db/db mice, but not in control mice. Compared with healthy mice, phosphorylation of p38, ErbB-1 and ErbB-3 was increased in diabetic mice, and neuregulin 1 treatment increased phosphorylation of p38 and ErbB-4. Conversely, the AKT/FOXO1 pathway was not affected by the 8-week treatment with NRG1.Conclusion: Diabetic mice showed altered NRG1-ErbB pathway in the liver compared with healthy mice. Moreover, chronic NRG1 treatment increased p38 phosphorylation in liver and improved glucose tolerance in diabetic mice, but not in control mice.

Neuregulin 1 improves complex 2-mediated mitochondrial respiration in skeletal muscle of healthy and diabetic mice.

It has been reported that neuregulin1 (NRG1) improves glucose tolerance in healthy and diabetic rodents. In vitro studies also suggest that NRG1 regulates myocyte oxidative capacity. To confirm this observation in vivo, we evaluated the effect on mitochondrial function of an 8-week treatment with NRG1 in db/db diabetic mice and C57BL/6JRJ healthy controls. NRG1 treatment improved complex 2-mediated mitochondrial respiration in the gastrocnemius of both control and diabetic mice and increased mitochondrial complex 2 subunit content by 2-fold. This effect was not associated with an increase in mitochondrial biogenesis markers. Enhanced ERBB4 phosphorylation could mediate NRG1 effects on mitochondrial function through signalling pathways, independently of ERK1/2, AKT or AMPK.

Neuregulin 1 Improves Glucose Tolerance in db/db Mice.

In vitro experiments using rodent skeletal muscle cells suggest that neuregulin 1 (NRG1) is involved in glucose metabolism regulation, although no study has evaluated the role of NRG1 in systemic glucose homeostasis. The purpose of this study was to investigate the effect of chronic and acute NRG1 treatment on glucose homeostasis in db/db mice. To this aim, glucose tolerance tests were performed in 8-week-old male db/db mice after treatment with NRG1 (50µg.kg-1) or saline 3 times per week for 8 weeks. In other experiments, glucose tolerance and pyruvate tolerance tests were performed in db/db mice 15 minutes after a single NRG1 (50µg.kg-1) or saline injection. Liver, adipose tissue, hypothalamus and skeletal muscle were also collected 30 minutes after acute NRG1 (50µg.kg-1) or saline treatment, and the phosphorylation status of the ERBB receptors, AKT (on Ser473) and FOXO1 (on Ser256) was assessed by western blotting. Chronic treatment (8 weeks) with NRG1 improved glucose tolerance in db/db mice. Acute treatment also lowered glycemia and insulinemia during glucose or pyruvate tolerance tests. NRG1 acute injection induced activation of ERBB3 receptors and phosphorylation of AKT and FOXO1 only in liver. Altogether, this study shows that acute and chronic NRG1 treatments improve glucose tolerance in db/db mice. This effect could be mediated through inhibition of hepatic gluconeogenesis.