Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation

Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.

The Role of Physical Aerobic Activity in Controlling Exercise-Induced Bronchoconstriction in Children and Adolescents with Asthma

Asthma, one of the major widespread chronic disorders among children and adolescents, has become more prevalent recently. The common manifestations of this disorder are caused by inflammatory airways that lead to airway restriction and lung hypersensitivity causing dry coughing, wheezing, and shortness of breath, all of which are combined with sleep disturbance, impaired physical activity, and reduced quality of life. The main goal of this brief review was to identify the associated variables that affect the management of asthma disease in children and young adolescents and to identify the role of physical aerobic exercise in the treatment of asthmatic children. The current review was based on prior research published in English databases such as Google Scholar, PubMed, and Embase in scientific articles published between January 2010 and October 2021 with the keywords "asthma," "children," "adolescents," "breathing episodes," "physical activity," and "physical exercise." Regular physical aerobic exercise training with moderate intensity has been shown to improve pulmonary functions, life quality, psychological conditions, and reduce asthma symptoms and EIB in children and adolescents with bronchial asthma.

Pathways in Skeletal Muscle: Protein Signaling and Insulin Sensitivity after Exercise Training and Weight Loss Interventions in Middle-Aged and Older Adults

Aging and obesity contribute to insulin resistance with skeletal muscle being critically important for maintaining whole-body glucose homeostasis. Both exercise and weight loss are lifestyle interventions that can affect glucose metabolism. The purpose of this study was to examine the effects of a six-month trial of aerobic exercise training or weight loss on signaling pathways in skeletal muscle in the basal condition and during hyperinsulinemia during a glucose clamp in middle-aged and older adults. Overweight and obese men and women aged 50–70 years were randomly allocated and completed six months of either weight loss (WL) (n = 18) or 3x/week aerobic exercise training (AEX) (n = 17). WL resulted in 10% weight loss and AEX increased maximal oxygen consumption (VO2max) (both p < 0.001). Insulin sensitivity (hyperinsulinemic-euglycemic 80 mU·m−2·min−1 clamp) increased in WL and AEX (both p < 0.01). In vivo insulin stimulation increased phosphorylation/total protein ratio (P/T) of protein kinase B (Akt), glycogen synthase kinase 3 beta (GSK-β3), 70 kDa ribosomal protein S6 kinase (p70S6k), insulin receptor substrate 1 (IRS-1), and insulin receptor (IR) expression (all p < 0.05) but not P/T extracellular regulated kinase ½ (ERK1/2), c-jun N-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38), or insulin-like growth factor 1 receptor (IGF-1R). There were differences between WL and AEX in the change in basal Akt P/T (p = 0.05), GSK-3β P/T ratio (p < 0.01), p70S6k (p < 0.001), ERK1/2 (p = 0.01) P/T ratio but not p38, JNK, IRS-1, and IGF-1R P/T ratios. There was a difference between WL and AEX in the insulin stimulation changes in GSK3 which increased more after WL than AEX (p < 0.05). In the total group, changes in M were associated with changes in basal total GSK-3β and basal total p70Sk as well as insulin stimulation of total p70Sk. Protein signaling in skeletal muscle provides insight as to mechanisms for improvements in insulin sensitivity in aging and obesity.

Metabolic Adaptations to Aerobic Exercise in Aged Mice

Aerobic exercise training is a potent intervention for the treatment and prevention of age-related disease, such as heart disease, obesity, and Type 2 Diabetes. Insulin resistance, a hallmark of Type 2 Diabetes, is reversed in response to aerobic exercise training. However, the effect of aerobic exercise training on glucagon sensitivity is unclear. Glucagon signaling at the liver promotes fatty acid oxidation, inhibits De novo lipogenesis, and activates AMP Kinase, a key mediator of healthy aging. Like humans, aging in mice age leads to a decline in physical and metabolic function. To understand the role of glucagon signaling in exercise-induced improvements in physical and metabolic function in the mouse, we implemented a 16-week aerobic exercise training protocol in young and aged mice. 16 weeks of exercise training initiated at 6 months of age increased markers of physical function (P&lt;0.01) and attenuated age-related weight gain (P&lt;0.05) and fat mass (P&lt;0.0001). Additionally, exercise training improved glucose clearance (P&lt;0.01), enhanced glucose-stimulated insulin secretion (P&lt;0.01) and decreased hepatic lipid accumulation (P&lt;0.05). Importantly, exercise training decreased hypoglycemia stimulated glucagon secretion (P&lt;0.01), with no effect on hepatic glucagon receptor mRNA expression or serum glucagon. Thus, we propose that aerobic exercise training enhances glucagon sensitivity at the liver, implicating glucagon as a potential mediator of exercise-induced improvements in aging. Studies initiating the same aerobic exercise training intervention at 18 months of age in the mouse are currently underway to establish the role of glucagon receptor signaling in exercise-induced improvements in aging.

Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle

Purpose: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated.Methods: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis.Results: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group.Conclusions: Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle.

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers’ cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

Health-Boosting Effects of Aerobic Exercise Training and Berberine on Diabetes: A Brief Overview

: Type 2 diabetes is one of the most important metabolic disorders that affect lifestyle. Accordingly, studies have shown that lifestyle changes, especially increasing daily physical activity, can prevent diabetes and help people with the disease through various mechanisms. On the other hand, the use of medicinal plants due to having various phytochemical compounds, each of which has healing properties, can be considered a helpful method in preventing and treating diabetes complications. One of the phytochemical compounds used as an effective substance in the treatment of diabetes is an alkaloid called Berberine. Berberine has been used in traditional medicine to lower blood glucose, and new studies in both in vivo and in vitro conditions have confirmed the diabetic effect of Berberine. Receiving increased energy metabolism, increased glucose and fatty acid uptake by peripheral tissues, improving lipid profile, reducing inflammatory mediators, increasing antioxidant capacity are common mechanisms that aerobic exercise and Berberine exert their beneficial effects in diabetes. In the present study, the effect of aerobic exercise, Berberine, and its combination on diabetes markers have been investigated considering the beneficial effects of aerobic exercise and Berberine in diabetes.

Effects of Isolated Soy Protein Supplementation Combined with Aerobic Exercise Training on Improving Body Composition, Anthropometric Characteristics and Cardiopulmonary Endurance in Women: A Pilot Study

Today, women are concerned with health promotion but also with improvements in body weight and shape. The purpose of this study was to investigate the effects of aerobic exercise training (AET) combined with isolated soy protein (ISP) supplementation on the body composition, anthropometric characteristics, and cardiopulmonary endurance of women. The qualified subjects were randomly assigned to AET or AET + ISP groups. Women in the AET + ISP group were given an ISP-rich supplement (40 g/day) 5 days a week for 8 weeks; those in the AET group were given the same amount of water in an identical manner. All women received 60 min of AET twice a week for 8 weeks at an intensity of 40–65% heart rate reserve (HRR) and their body composition, anthropometric characteristics, and physical fitness were measured one week before and after the 8-week AET class. A total of 16 subjects (age: 36.13 ± 5.76 years) completed the study and were included in the dataset. The results of this study show that the AET + ISP group obtained greater reductions in body weight (effect size = 0.99), body mass index (BMI, effect size = 1.04), percentage body fat (PBF, effect size = 1.18), circumferences (waist and hip, all effect sizes > 0.8), and greater gains in the percentage lean body mass (PLBM, effect size = 0.89), compared with the AET group, without significant differences in 20 m multi-stage shuttle run test (20 m MST). We conclude that there is a trend for the consumption of ISP following AET to improve the body composition and anthropometric characteristics in women, compared with those who received the same AET without ISP supplementation.