۱- Introduction

۲- Materials and methods

۳- Statistical analysis

۴- Results

۵- Discussion

۶- Conclusions

References

Abstract

Benefits of exercise have been documented for many diseases with a chronic progression, including obesity, diabetes mellitus, cardiovascular diseases, neurodegenerative diseases, certain types of cancers, and overall mortality. Low-grade systemic inflammation is a key component of these pathologies and it has been demonstrated that can be prevented by performing regularly physical exercise. The aim of this study was to examine the effect of lipopolysaccharide (LPS)-induced inflammation on glucose and insulin tolerance, exercise performance, production of urinary neopterin and striatal neurotransmitters levels in adult male C57BL/6 mice. Increased blood glucose clearance and insulin sensitivity were observed after a single administration of glucose (2 g/kg, p.o.) or insulin (0.5 U/kg, i.p.). However, the repeated injection of LPS (0.33 mg/kg/day, i.p.) decreased glucose tolerance and increase urinary neopterin levels, pointing to systemic inflammation. In parallel to the urinary-increased neopterin, it was observed a significant reduction in the striatal dopamine levels and an increase in the serotonin/dopamine ratio. While a single LPS injection (0.33 mg/kg, i.p.) showed impaired performance in the incremental loading test (10 m/min, with 2 m/min increment every 3 min, at 9% grade), a moderate physical exercise protocol (treadmill for three weeks; 5 sessions/week; up to 50 min/day) prevented the exacerbation of immune system activation and preserved mitochondrial activity in skeletal muscle from mice with continuous LPS infusion (infusion pumps: 0.83 mg/kg/day, i.p.). In conclusion, the peripheral-induced inflammation elicited metabolic alterations that provoked impairment in striatal dopamine metabolism. The moderate exercise prevented the increase of urinary neopterin and preserved mitochondrial activity under LPS-induced inflammatory conditions.

Introduction

Physical inactivity and sedentary behavior have become a major public health concern since they represent the second leading single cause of death in the United States [1,2]. A sedentary lifestyle is a major risk factor for many chronic pathologies, including obesity, diabetes, cardiovascular diseases, certain types of cancers, and overall mortality, where the benefits of physical exercise have been extensively documented [3–۵]. Animal models have contributed to the understanding and development of current clinical treatments for chronic diseases [6–۸]. In addition, basic research is necessary when humans studies have limitations and ethical implications [9]. In this sense, it has been demonstrated that regular exercise brings a number of mental and physical health benefits, including reduced risk of developing diabetes mellitus, obesity, heart disease, metabolic syndromes and cancer [10,11] Many chronic diseases are associated with persistent and low-grade inflammation [12]. For example, the infiltration of immune cells into white adipose tissue, and therefore inflammation in this tissue, is closely correlated with the development of insulin resistance and type 2 diabetes mellitus (T2DM) [13]. In this context, it is known that patients with T2DM present a higher incidence of development of neurodegenerative diseases [14–۱۷]. T2DM individuals have an increased risk of dementia by 40%, and it has been associated with cognitive decline and reduced hippocampal volume [18]. Several neurodegenerative diseases are also linked to inflammation. Neuroinflammation affects the activation of glial cells and the subsequent release of inflammatory cytokines such as tumor-necrosis factor-α (TNF-α). These cytokines are thought to promote the death of dopamine (DA)-containing neurons in the substantia nigra region of the brain, thereby contributing to the pathology of Parkinson’s disease (PD) [19,20]. In addition, it has also been postulated the involvement of the inflammation in the etiology of Alzheimer’s disease (AD; for a review see [21]). It should be noted that in addition to the brain inflammation found in many neurodegenerative diseases, systemic inflammation further exacerbates these diseases and promotes the progression to neurodegeneration [22].