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.

This study shows that NRG1 has a possible glucose-lowering effect in the liver and via an ErbB3/AKT signaling pathway. This NRG1 effect is also maintained in old rats, suggesting that the NRG1/ErbB signaling pathway might represent a promising therapeutic target in insulin resistance states.

Aim. -Studies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice.Methods. -Weight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50 g/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks.Results. -Leptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment.Conclusion. -The decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

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.

Key pointsr Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents.r 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.r We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. r 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.r 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.

Limited evidence exists demonstrating reliability of using direct measures to quantify punching velocity. The aim of this study was to establish the intra- and inter-day reliability of a linear positional transducer (GymAware) and accelerometer (PUSH Band 2.0) for the quantification of peak punching velocity in trained junior boxing athletes. Eighteen males aged 16.7 years (±1.2) with at least two years of boxing experience participated in the study. On two separate days, participants performed five dominant-hand crosses with maximal effort. Ordinary least-products regression analysis was used to compare mean and maximum peak velocity scores between devices within each day of testing. Two-way mixed intraclass correlation coefficients (ICC3,1) and Pearson’s r with 95% confidence intervals (95%CI) were also used to compare mean and maximum peak velocity within devices across days. Maximum peak (∼7.5 ms vs. ∼6.2 ms) and mean peak (∼7.0 ms vs. 5.4 ms) velocity was higher when measured via GymAware compared to PUSH Band 2.0 on both days (all P ≤ 0.012). The within-device mean (ICC3,1 = 0.871, 95%CI  =  0.689, 0.950) and maximum (ICC3,1 =  0.853 95%CI  =  0.650, 0.942) peak velocity scores for the GymAware across Days 1 and 2 demonstrated very high reliabilities. Mean (ICC3,1 = 0.309, 95%CI = –0.170, 0.670) and maximum (ICC3,1 = 0.227, 95%CI = –0.173, 0.637) peak velocity for PUSH Band 2.0 demonstrated weak reliabilities. Proportional bias was found for Day 2 mean and maximum peak velocity and when both days were pooled. Fixed bias was observed for mean (Day 1) and maximum peak velocity when both days were pooled. These results may provide useful information for professionals working with boxing or combat-sport athletes.

No abstract

No abstract