Exercise Training Combined With A Well-balanced Diet Activates Nrg1 Pathway In Gastrocnemius Of Obese Rats

Meeting Abstract: 1519 Volume: 47 Issue: 5 Supplement 1Exercise Training Combined With A Well-balanced Diet Activates Nrg1 Pathway In Gastrocnemius Of Obese Rat

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

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. 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 16weeks. 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 8weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16week 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

J Natl Cancer Inst

BACKGROUND: Using the large nationwide CANTO cohort, we assessed cognitive functioning change after cancer treatments in a subgroup of breast cancer patients. METHODS: We included patients with newly diagnosed invasive stage I-III breast cancer enrolled in the CANTO sub-study focused on cognitive evaluation and healthy control women matched for age and education. Episodic and working memory, executive functions, processing speed, attention, self-report cognitive difficulties (SRCD), fatigue, anxiety/depression were assessed with neuropsychological tests and self-report questionnaires, before treatment (baseline), about 1 (year-1) and 2 years (year-2) after diagnosis. We used linear mixed models to study changes in cognition and tested the effect of adjuvant chemotherapy. RESULTS: We studied 276 localized breast cancer patients (62% chemotherapy (CT+)) compared to 135 healthy controls. After adjustment, patients had lower baseline working memory, processing speed and attention scores than healthy controls (p ≤ 0.001), and the difference remained significant over follow-up for working memory and processing speed. Executive function scores were similar between groups at baseline but decreased at year-1 among patients compared to healthy controls (p for change = 0.006). This decrease in CT+ patients was significant when compared to healthy controls scores (p for change < 0.001). After adjustment, SRCD were similar between breast cancer patients and healthy controls at baseline but increased in patients after treatment at year-1 (p for change = 0.002). CONCLUSIONS: Cognitive difficulties are an important concern in breast cancer patients, starting at diagnosis. Cancer treatments induce executive function decline and SRCD, which decrease over follow-up.Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cance