Current Pharmaceutical Design - Volume 26, Issue 9, 2020

Background: Frail individuals experience an accelerated immunosenescence, and exercise has been identified as a therapy to promote a better inflammatory environment. Objective: To analyze the effects of 28-weeks of two different exercise protocols on the functional fitness and immune profiles of institutionalized pre-frail and frail women with mild cognitive impairment. Methods: Participants residing in care homes (n=60, 81±7.84 years old) were randomized into three groups: a chair elastic band muscle-strength exercise (CSE, n=21; 81±4.79), a chair multimodal exercise (CME, n=20; 80±8.19), and a control non-exercise (CGne, n=19; 80±10.01). Both CME and CSE groups performed progressive circuit-training exercise sessions. The controls did not change their usual lifestyle. The Fried protocol and the Mini-Mental State Examination questionnaire were used to identify the frail subgroups and the participants with mild cognitive impairment. Data for anti and pro-inflammatory markers and physical fitness were analyzed pre and post-interventions. Results: After the intervention, a significant effect of time and time by group for sIgA and time by group for IL- 10 levels were found (p > 0.05). Within-group analysis showed a significant moderate decrease in the TNF-α to IL-10 ratio for the CME group and an increase in the controls (p > 0.05) and a slight reduction in the IL-6 and IL- 1β concentrations. The controls showed a negative trend towards a decrease in physical fitness and a trend for increased levels in the pro-inflammatory markers IL-6 and IL-1β. Conclusion: The evidence regarding the use of systematic and moderate long-term exercise as therapy for promoting a better balance between pro- and anti-inflammatory environments and a decrease in the inflammatory index for the CME group were the most promising results from this study.

Background: The number of individuals with obesity is growing worldwide and this is a worrying trend, as obesity has shown to cause pathophysiological changes, which result in the emergence of comorbidities such as cardiovascular disease, diabetes mellitus type 2 and cancer. In addition, cognitive performance may be compromised by immunometabolic deregulation of obesity. Although in more critical cases, the use of medications is recommended, a physically active lifestyle is one of the main foundations for health maintenance, making physical training an important tool to reduce the harmful effects of excessive fat accumulation. Aim: The purpose of this review of the literature is to present the impact of immunometabolic alterations on cognitive function in individuals with obesity, and the role of exercise training as a non-pharmacological approach to improve the inflammatory profile, energy metabolism and neuroplasticity in obesity. Method: An overview of the etiology and pathophysiology of obesity to establish a possible link with cognitive performance in obese individuals, with the executive function being one of the most affected cognitive components. In addition, the brain-derived neurotrophic factor (BDNF) profile and its impact on cognition in obese individuals are discussed. Lastly, studies showing regular resistance and/or aerobic training, which may be able to improve the pathophysiological condition and cognitive performance through the improvement of the inflammatory profile, decreased insulin resistance and higher BDNF production are discussed. Conclusion: Exercise training is essential for reestablishment and maintenance of health by increasing energy expenditure, insulin resistance reduction, anti-inflammatory proteins and neurotrophin production corroborating to upregulation of body function.

Background: Chronic diseases, such as obesity and cancer, have high prevalence rates. Both diseases have hyperinsulinemia, hyperglycemia, high levels of IGF-1 and inflammatory cytokines in common. Therefore, these can be considered triggers for cancer development and growth. In addition, low-grade inflammation that modulates the activation of immune cells, cellular metabolism, and production of cytokines and chemokines are common in obesity, cancer, and insulin resistance. Pharmacological strategies are necessary when a change in lifestyle does not improve glycemic homeostasis. In this regard, thiazolidinediones (TZD) possess multiple molecular targets and regulate PPARγ in obesity and cancer related to insulin resistance, while metformin acts through the AMPK pathway. Objective: The aim of this study was to review TZD and metformin as pharmacological treatments for insulin resistance associated with obesity and cancer. Conclusion: Thiazolidinediones restored adiponectin secretion and leptin sensitivity, reduced lipid droplets in hepatocytes and orexigen peptides in the hypothalamus. In cancer cells, TZD reduced proliferation, production of reactive oxygen species, and inflammation by acting through the mTOR and NFΚB pathways. Metformin has similar effects, though these are AMPK-dependent. In addition, both drugs can be efficient against certain side effects caused by chemotherapy.

Type 1 diabetes is characterized by an autoimmune β-cell destruction resulting in endogenous insulin deficiency, potentially leading to micro- and macrovascular complications. Besides an exogenous insulin therapy and continuous glucose monitoring, physical exercise is recommended in adults with type 1 diabetes to improve overall health. The close relationship between physical exercise, inflammation, muscle contraction, and macronutrient intake has never been discussed in detail about type 1 diabetes. The aim of this narrative review was to detail the role of physical exercise in improving clinical outcomes, physiological responses to exercise and different nutrition and therapy strategies around exercise. Physical exercise has several positive effects on glucose uptake and systemic inflammation in adults with type 1 diabetes. A new approach via personalized therapy adaptations must be applied to target beneficial effects on complications as well as on body weight management. In combination with pre-defined macronutrient intake around exercise, adults with type 1 diabetes can expect similar physiological responses to physical exercise, as seen in their healthy counterparts. This review highlights interesting findings from recent studies related to exercise and type 1 diabetes. However, there is limited research available accompanied by a proper number of participants in the cohort of type 1 diabetes. Especially for this group of patients, an increased understanding of the impact of physical exercise can improve its effectiveness as an adjuvant therapy to move (forward).

Type 2 diabetes (T2D) is among the most prevalent non-communicable lifestyle diseases. We propose that overnutrition and low levels of physical activity can contribute to a vicious cycle of hyperglycemia, inflammation and oxidative stress, insulin resistance, and pancreatic β-cell dysfunction. The pathophysiological manifestations of T2D have a particular impact on the vasculature and individuals with T2D are at high risk of cardiovascular disease. Targeting aspects of the vicious cycle represent therapeutic approaches for improving T2D and protecting against cardiovascular complications. The recent advent of exogenous oral ketone supplements represents a novel, non-pharmacological approach to improving T2D pathophysiology and potentially protecting against cardiovascular disease risk. Herein, we review the emerging literature regarding the effects of exogenous ketone supplementation on metabolic control, inflammation, oxidative stress, and cardiovascular function in humans and highlight the potential application for breaking the vicious cycle of T2D pathophysiology.

Cancer patients display systemic inflammation, which leads to an increase in protein catabolism, thus promoting the release of free amino acids to further support metabolism and remodelling of muscle proteins. Inflammation associated with tumor growth leads to malnutrition, a factor that increases the risk of developing cachexia. With cancer-induced cachexia, nutritional interventions have gained traction as a preventative method to manage this condition. Currently, cancer consensus recommendations suggest a protein intake above 1.0 g/kg.day-1 up to 2.0 g/k.day-1 for cancer patients, although an ideal amount for some amino acids in isolation has yet to be determined. Due to controversy in the literature regarding the benefits of the biochemical mechanisms of various muscle mass supplements, such as L-leucine (including whey protein and BCAA), β-hydroxy-beta-methyl butyrate (HMβ), arginine, glutamine and creatine, several studies have carefully examined their effects. L-leucine and its derivatives appear to regulate protein synthesis by direct or indirect activation of the mTORC1 pool of kinases, further promoting muscle protein balance. Arginine and glutamine may act by reducing inflammation and infection progression, thus promoting improvements in food intake. Creatine exerts anabolic activity, acting as an immediate energy substrate to support muscle contraction further increasing lean mass, mainly due to greater water uptake by the muscle. In this narrative review, we highlighted the main findings regarding protein consumption and amino acids to mitigate cancer-induced skeletal muscle depletion.

A lack of physical activity is linked to the development of many chronic diseases through a chronic low-grade inflammation state. It is now well accepted that the immune system plays a central role in the development of several chronic diseases, including insulin resistance, type 2 diabetes, atherosclerosis, heart failure and certain types of cancer. Exercise elicits a strong anti-inflammatory response independently of weight loss and can be a useful non-pharmacologic strategy to counteract the low-grade inflammation. The CD4+CD25+CD127- FoxP3+ Regulatory T (Treg) cells are a unique subset of helper T-cells, which regulate immune response and establish self-tolerance through the secretion of immunoregulatory cytokines, such as IL-10 and TGF-β, and the suppression of the function and activity of many immune effector cells (including monocytes/macrophages, dendritic cells, CD4+ and CD8+ T cells, and Natural Killers). The metabolic phenotype of Tregs are regulated by the transcription factor Foxp3, providing flexibility in fuel choice, but a preference for higher fatty acid oxidation. In this review, we focus on the mechanisms by which exercise - both acute and chronic - exerts its antiinflammatory effects through Treg cells mobilization. Furthermore, we discuss the implications of immunometabolic changes during exercise for the modulation of Treg phenotype and its immunosuppressive function. This narrative review focuses on the current knowledge regarding the role of Treg cells in the context of acute and chronic exercise using data from observational and experimental studies. Emerging evidence suggests that the immunomodulatory effects of exercise are mediated by the ability of exercise to adjust and improve Tregs number and function.