BACKGROUNDSuppression of myostatin (MSTN) has been associated with skeletal muscle atrophy and insulin resistance (IR). However, few studies link MSTN suppression by ladder-climbing training (LCT) and IR. Therefore, we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.

METHODSThe rats were randomly assigned to two types of diet: normal pellet diet (NPD, n = 8) and high-fat diet (HFD, n = 16). After 8 weeks, the HFD rats were randomly re-assigned to two groups (n = 8 for each group): HFD sedentary (HFD-S) and high-fat diet ladder-climbing training (HFD-LCT). HFD-LCT rats were assigned to LCT for 8 weeks. Western blotting, immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN, GLUT4, PI3K, Akt and Akt-activated targets (mTOR, FoxO1 and GSK-3β).

RESULTSThe LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats. MSTN protein levels decreased in matching serum (42%, P = 0.007) and muscle samples (25%, P = 0.035) and its receptor mRNA expression also decreased (16%, P = 0.041) from obese rats after LCT. But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups (P = 0.074). The ladder-climbing training significantly enhanced PI3K activity (1.7-fold, P = 0.024) and Akt phosphorylation (83.3%, P = 0.022) in HFD-fed rats, significantly increased GLUT4 protein expression (84.5%, P = 0.036), enhanced phosphorylation of mTOR (4.8-fold, P < 0.001) and inhibited phosphorylation of FoxO1 (57.7%, P = 0.020), but did not affect the phosphorylation of GSK-3β.

CONCLUSIONSThe LCT significantly reduced IR in diet-induced obese rats. MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.

Animals ; Blotting, Western ; Diet, High-Fat ; adverse effects ; Glucose Tolerance Test ; Glucose Transporter Type 4 ; metabolism ; Immunohistochemistry ; Insulin Resistance ; physiology ; Male ; Myostatin ; metabolism ; Obesity ; etiology ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Quadriceps Muscle ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective    To analyze the short-term and long-term efficacy of staged coronary artery bypass grafting (CABG) and carotid artery stenting (CAS) compared with CABG alone in patients with coronary heart disease with preoperative history of stroke and carotid stenosis. Methods    We reviewed the clinical data of 55 patients (48 males, 7 females, aged 67.62±7.06 years) with coronary heart disease and carotid stenosis who had a history of stroke and underwent CABG+CAS or CABG alone in Zhongshan Hospital from 2008 to 2017. There were 13 patients in the staged CABG+CAS group and 42 patients in the CABG alone group. The differences in the incidence of perioperative adverse events and long-term survival between the two groups were studied, and univariate and multivariate analyses were carried out to determine the independent risk factors of long-term adverse events. Results     Perioperative adverse events occurred in 1 (7.69%) patient of the staged CABG+CAS group, and 4 (9.52%) patients of the CABG alone group (P=0.84). During the follow-up period (67.84±37.99 months), the long-term survival rate of patients in the staged CABG+CAS group was significantly higher than that in the CABG alone group (P=0.02). The risk of long-term adverse events in the staged CABG+CAS group was 0.22 times higher than that in the CABG alone group (95%CI 0.05-0.92, P=0.04). Conclusion    Staged CABG+CAS can significantly improve the long-term survival prognosis without increasing the perioperative risk. It is a safe and effective treatment, but prospective randomized studies are still needed to further confirm this finding.