Mechanical stretch improves high glucose-induced leptin resistance thus promoting glucose uptake of C2C12 myoblasts.

Exercise has been shown to alleviate central leptin resistance (LR), while the effects of exercise on peripheral especially skeletal muscle LR and its mechanisms remain poorly understood. In this study, we explored the effect and mechanisms of mechanical stretch (mimic exercise in vitro) on high glucose-induced LR of C2C12 myoblasts. We found (1) 65 mM glucose-induced LR of C2C12 cells was improved by 15 % stretch lasting for 3 or 6 h (represented as decrease of leptin and increases of leptin receptor (LepR) and glucose uptake), with more glucose uptake in 6h-stretch than 3h-stretch; (2) 15 % stretch changed the levels of important regulators of LR, including increasing signal transducer and activator of transcription 3 (STAT3), decreasing protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling-3 (SOCS3), with higher alterations of STAT3 and SOCS3 in 6h-stretch than 3h-stretch; (3) 15 % stretch activated the classical pathway regulating glucose metabolism, including increasing the levels of insulin-like growth factor (IGF-1), IGF-1 receptor (IGF-1R), insulin receptor substrate 1 (IRS-1), protein kinase B (Akt) and glucose transporter 4 (GLUT4), enhancing activities of phosphoinositide 3-kinase (PI3K) and Akt, with more increases of IGF-1R and IRS1 in 6h-stretch than 3h-stretch and enhanced GLUT4 only in 6h-stretch.

Exercise improves glucose and lipid metabolism in high fat diet feeding male mice through androgen/androgen receptor-mediated metabolism regulatory factors.

Exercise alleviates high fat diet (HFD)-induced glycolipid metabolism disorders, but the mechanisms are not discovered totally. Low androgen/androgen receptor (AR) levels are associated with glycolipid metabolism disorders in males, and androgen/AR modulate glycolipid metabolism-related regulators such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-α), Forkhead box O1 (FoxO1), phosphoenolpyruvate carboxy kinase (PEPCK) and stearyl-coenzyme A desaturase 1 (SCD1). In the present study, we blockaded androgen (by castration) and inhibited or activated AR activity (by AR antagonist flutamide and agonist S4, respectively) to clarify androgen/AR's roles in exercise-induced alleviation of glycolipid metabolism disorders in male high fat diet (HFD) feeding mice and the underlying mechanisms.

Androgen receptor regulates the differentiation of myoblasts under cyclic mechanical stretch and its upstream and downstream signals.

Our previous studies have demonstrated the important roles of androgen receptor (AR) in myoblast proliferation regulated by 15 % (mimic appropriate exercise) and 20 % (mimic excessive exercise) mechanical stretches. Except for myoblast proliferation, differentiation is also an important factor affecting muscle mass and strength. But the role of AR in stretch-regulated myoblast differentiation and AR's upstream and downstream signals remain unknown.

Chemerin influences blood lipid of aged male mice under high fat diet and exercise states through regulating the distribution and browning of white adipose tissue.

Background: With aging, white adipose tissue (WAT) undergoes distribution change and browning inhibition, which could be attenuated by exercise. Adipokine chemerin exerts roles in the above changes of WAT, and our previous studies demonstrated the effect of decreased chemerin on exercise-induced improvement of glucose and lipid metabolism in high fat diet (HFD) feeding male mice, so this study is to clarify whether chemerin's effects on glucose and lipid metabolism are associated with the distribution and browning of WAT.

Methods: After diet and exercise interventions, body weight and adipose tissue contents in different depots of male mice were weighed, body composition and energy metabolism parameters were determined by Echo MRI Body Composition Analyzer and metabolic cage, respectively.

Aerobic Exercise Attenuates Pressure Overload-Induced Cardiac Dysfunction through Promoting Skeletal Muscle Microcirculation and Increasing Muscle Mass.

Background: Aerobic exercise has been proven to have a positive effect on cardiac function after hypertension; however, the mechanism is not entirely clarified. Skeletal muscle mass and microcirculation are closely associated with blood pressure and cardiac function.

Objective: This study was designed to investigate the effects of aerobic exercise on the skeletal muscle capillary and muscle mass, to explore the possible mechanisms involved in exercise-induced mitigation of cardiac dysfunction in pressure overload mice.

Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways.

Background: Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR's role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified.

Methods: Firstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch.

Effects of Cyclic Mechanical Stretch on the Proliferation of L6 Myoblasts and Its Mechanisms: PI3K/Akt and MAPK Signal Pathways Regulated by IGF-1 Receptor.

Myoblast proliferation is crucial to skeletal muscle hypertrophy and regeneration. Our previous study indicated that mechanical stretch altered the proliferation of C2C12 myoblasts, associated with insulin growth factor 1 (IGF-1)-mediated phosphoinositide 3-kinase (PI3K)/Akt (also known as protein kinase B) and mitogen-activated protein kinase (MAPK) pathways through IGF-1 receptor (IGF-1R). The purpose of this study was to explore the same stretches on the proliferation of L6 myoblasts and its association with IGF-1-regulated PI3K/Akt and MAPK activations.

Role of androgen receptor on cyclic mechanical stretch-regulated proliferation of C2C12 myoblasts and its upstream signals: IGF-1-mediated PI3K/Akt and MAPKs pathways.

Objects: To detect the effects of androgen receptor (AR) on cyclic mechanical stretch-modulated proliferation of C2C12 myoblasts and its pathways: roles of IGF-1, PI3K and MAPK.

Methods: C2C12 were randomly divided into five groups: un-stretched control, six or 8 h of fifteen percent stretch, and six or 8 h of twenty percent stretch. Cyclic mechanical stretch of C2C12 were completed using a computer-controlled FlexCell Strain Unit.